AHVMA Journal - Volume 63 by Redstone Media Group

JOURNAL American Holistic Veterinary Medical Association Volume 63, Summer 2021

The Leader • The Voice • The Resource

AHVMA Journal • Volume 63 Summer 2021

American Holistic Veterinary Medical Association OFFICERS President Colleen Smith, DVM Chattanooga, TN President-Elect Diana Drumm, DVM San Diego, CA Vice President Alli Dunlop, DVM Milwaukee, WI Past President Neal J. Sivula, DVM, PhD, MDiv Richfield, OH Secretary Theresa SaLee, DVM Lisle, IL Treasurer Ashley Rossman, DVM Glenview, IL

JOURNAL American Holistic Veterinary Medical Association Volume 63, Summer 2021

BOARD OF DIRECTORS

ISSN 2474-1906

Janet Gordon Palm, DVM Fruita, CO

Editor-in-Chief Shelley R. Epstein, VMD Media, PA Editor-jahvma@ahvma.org

Sue Howell, DVM Thiensville, WI

Editors Emeriti Bernie Fischer, DVM, PhD; Nancy Scanlan, DVM

Jeffrey Judkins, DVM Jacksonville, OR

Copy Editors Laurin Cooke, DVM Lynn Shiner, DVM

Ronald Koh, DVM Sacramento, CA Rosemarie Niznik, DVM Bristol, WI Caroline Pattie, DVM Falls Church, VA AHVMA Executive Director Charles H. Emely, PhD, CAE Hockessin, DE

Jennifer Hutchinson Brenda Smith, DVM

Editorial Committee Chairperson: Shelley Epstein, VMD, Media, PA Bernie Fischer, DVM, Ph.D., Durham, NC Laurin Cooke, DVM, Black Mountain, NC W. Jean Dodds, DVM, Garden Grove, CA Laurie Dohmen, VMD, MS, Hartly, DE Kristy Herman, DVM, New City, NY Nora Jean Nealon, DVM, PhD, Colombus, OH Carla Salido, DVM, Eugene, OR Nancy Scanlan, DVM, Mount Shasta, CA Lea Stogdale, DVM, Winnipeg, MB, Canada Lynn Shiner, DVM, Corpus Christi, TX Instructions for Authors The Journal of the American Holistic Veterinary Medical Association is published four times a year and welcomes manuscripts dealing with any aspect of holistic, alternative, or complementary veterinary medicine. For more information, go to: AHVMA.org/journal-submissions

AHVMA COMMITTEES AVMA DELEGATES Dirk Yelinek, DVM Redondo Beach, CA Gary Stuer, DVM Bethel, ME CONFERENCE PROGRAM COMMITTEE Chair: Carol Falck, VMD Cleveland, GA Jennifer Levitsky, DVM Severna Park, MD Julie Sturm, DVM Ponte Vedra Beach, FL Lisa Fox Wright, DVM Wellington, OH ISSUES COMMITTEE Chair: Alli Dunlop, DVM Milwaukee, WI NOMINATING COMMITTEE Chair: Neal J. Sivula, DVM, PhD, MDiv Richfield, OH

FINANCE COMMITTEE Chair: Diana Drumm, DVM San Diego, CA Ashley Rossman, DVM Glenview, IL Neal J. Sivula, DVM, PhD, MDiv Richfield, OH Colleen Smith, DVM Chattanooga, TN Executive Director/CEO AHVMA (Ex-officio): Charles H. Emely, PhD SAHVMA AHVMA Operations Director (Ex-officio): Melissa Kellagher Abingdon, MD Mandie Emely Abingdon, MD Gabrielle Pagana Chino, CA

American Holistic Veterinary Medical Association PO Box 630, Abingdon, MD 21009 Phone: 410.569.0795 • Fax: 410.569.2346 Office@AHVMA.org

COUNCIL OF ELDERS Chair: Angel Mitchell, DVM Columbus, NC

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American Holistic Veterinary Medical Association AHVMA Journal • Volume 63 Summer 2021

JOURNAL American Holistic Veterinary Medical Association Volume 63, Summer 2021

“Leo and Keeks” (11 x 14 in, watercolor on paper) Lauren Butare Smith, DVM is a fine artist specializing in detailed watercolor portraits and paintings. Prior to her career as an artist, Dr. Butare Smith was a small animal veterinarian. After becoming severely disabled for over a decade following a bartonella infection, she pursued her love of art, with her passion for animals enabling her to capture the essence of each animal subject. “Leo and Keeks” was commissioned by Gillian Blair as a surprise for her daughter, owner of the cats featured. Dr. Butare Smith resides in Durham, NC with her family. Copyright © 2021 American Holistic Veterinary Medical Association. All Rights Reserved.

Without limiting the rights under copyright reserved above, no part of this publication may be reproduced, stored in or introduced into a retrieval system, or transmitted, in any form, or by any means, without the prior written permission of the individual author and the publisher of this Journal.

AHVMA Membership

(See membership form page 64)

The mindful leader elevating the veterinary profession through innovation, education, and advocacy of integrative medicine. The Leader, The Voice, The Resource.

Scientific Reviews

10. . . . . Integrative Treatment of Canine Cognitive Dysfunction Janice L. Huntingford, DVM, MS

23. . . . . A cupuncture for the Treatment of Neuromuscular Conditions in Dogs and Cats, with Emphasis on Intervertebral Disc Disease Bonnie D. Wright, DVM

34. . . . . Vibrational Medicine: The Tuning Fork as a Therapeutic Modality

Jennifer M. Hebel, DVM, PhD

44. . . . . The Role of Movement and Physical Rehabilitation in Connective Tissue Maintenance and Healing Jo L. Moyes, LVMT Pedro L. Rivera, DVM

Graduate Veterinarians (includes Journal and Conference Proceedings): US $226.00 Veterinary Students (Dean’s Letter Required): Complimentary

(Note: Canadian and international members who wish to receive the print copy of the Journal are charged higher fees to cover mailing costs; see Web site or contact office for details.) Journal Subscription Only (Non-Veterinarians): $95.00

A brochure and membership application may be obtained by contacting the AHVMA office at: Voice: 410-569-0795, Fax: 410-569-2346, E-mail: office@AHVMA.org.

Information and membership application may also be obtained online at the AHVMA website: AHVMA.org

AHVMA Journal • Volume 63 Summer 2021

Table of Contents From The Literature

also in this issue

50. . . .

6 . . . . .

Editor's Introduction

8 . . . . .

President’s Letter

55. . . .

2021 AHVMA Conference Sponsors

56. . . .

2021 AHVMA Conference

58. . . .

2021 AHVMA Conference Schedule

62. . . .

2021 AHVMA Conference Registration Form

64. . . .

AHVMA Membership Form

Summary by W. Jean Dodds, DVM

66. . . .

ACVBM and VBMA Update

Efficacy of Wu Mei Wan for Treating

67. . . .

Council of Elders

68. . . .

Classifieds

69. . . .

Standard Abbreviations

Quantitative Translation of

Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome Reviewed by Bernard M. Fischer, DVM, PhD

51. . . .

O rigins and Genetic Legacy of Prehistoric Dogs Of Dogs and Men Reviewed by Kristy Herman, DVM

52. . . .

53. . . .

A ssisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence

Equine Metabolic Syndrome Related Laminitis and Uveitis Poorly Responsive to Conventional Medicine Reviewed by Nancy Scanlan, DVM

54. . . .

race Element Levels in Serum T Are Potentially Valuable Diagnostic Markers in Dogs Reviewed by Lea Stogdale, DVM

AHVMA Journal • Volume 63 Summer 2021

Editor's Introduction For this column, I’m going to share two parables. The first you’ve heard in many versions, with the contemporary one going something like this:

A man is fishing in the middle of the ocean when his boat starts to take on water. A fishing vessel happens by and offers to rescue him. The man declines, stating, “God will save me.” Hours later, as the situation becomes more dire, a cruise ship spots the man and offers to save him. Again, the man declares, “God will save me.” Shortly thereafter, a helicopter appears over the struggling fisherman, prepared to save him. Yet again, the man insists, “God will save me.” The man drowns and confronts God in Heaven: “All my life I’ve believed in you, but you let me down!” God responds, “I sent you a fishing vessel, a cruise ship, and a helicopter.” The pandemic has brought a year of hardships and catastrophes. I, like many of my holistic colleagues, have quietly struggled with the issue of whether or not to get the COVID-19 vaccination. The last vaccine I received was a rabies booster circa 1985, shortly after vet school graduation. Nine years later, I would be enmeshed in the holistic world with discoveries of new ways of achieving health for my patients, family, and me. I could recite just about every study that demonstrated vaccine adverse events, and as a veterinary homeopath, I treated plenty of small-animal vaccinosis cases. I know the history of success in treating people with homeopathy during epidemics, and I understand how the homeopathic concept of genus epidemicus prepared our current homeopathic community to tackle this pandemic.

However, chronic illness is rampant in the United States. Blame it on diet and obesity, lack of exercise, the conventional medical model that focuses on managing or removing symptoms rather than making the individual healthy, or a myriad of other factors, but the reality is that the SARS-CoV-2 virus found fertile ground here, and the urgency of halting the spread and saving lives would not be achieved on any great scale with our holistic armament. The vaccines would be our lifeline. 6

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Being healthy with no underlying conditions, I was more worried about those around me—my family, friends, and coworkers with preexisting conditions—and the fact that I could be transmitting the virus for days before I became symptomatic. I work at two animal shelters, and I was very concerned that I would be the one who shut them both down. I did not want to unwittingly give the virus to loved ones and high-risk individuals. And I was ready for my freedom.

Then there are the people I highly respect. My brother-inlaw, a pediatrician who 34 years ago inspired me to take a critical look at vaccination and whose practice consists of many parents who do not want to vaccinate, participated in the Pfizer vaccine trial. My college roommate, a professor and dear friend, volunteered to be, as she called it, a “guinea pig” in the Johnson & Johnson vaccine trial. These role models understand the necessity.

Meanwhile, my friends—frontline conventional doctors and nurses—were putting their lives at risk. My emergency physician friend pleaded with everyone to get vaccinated.

And given the skepticism about vaccines embedded with new technology resulting in their provisional approval in record time, I was impressed with the public access to the scrutiny of the safety and remarkable performance of the vaccines.

Dogma gave way to the greater good. On March 12, I received my liberating second dose. My reaction was relatively mild and dispelled with one dose of homeopathic Rhus tox 200C at 4 am.

Now for the second parable. Today, I went on one of my first bike rides of the year. On the way home, I noticed a black bird flying solo. It cast a shadow over me as it flew silently past. I remarked to my companion how the “crow” must not have seen us as a threat, as it did not call out our presence to its flock. My companion corrected me: This was a buzzard, not a crow. And it flew disinterestedly over me.

April 5, 2021

Shelley R. Epstein, VMD

Editor-in-Chief Editorial Committee Chairperson

AHVMA Journal • Volume 63 Summer 2021

President’s Letter

Welcome to our summer issue. I hope everyone is thriving, peaceful, and optimistic as we move into warmer weather and a new outlook on community. I feel we are learning to embrace what shows up a little more consciously. Our landscape has been changed permanently, but I am confident that energetically our world will be a much healthier place. I am so excited for our upcoming conference in Reno, Nevada. It will be an amazing gathering and celebration of knowledge, friendship, and revitalization. The Conference will be a great spot to shake off the dust from a year of uncertainty as we focus again on becoming the best healers we can be. Our Conference committee has outdone itself again with stellar topics and speakers. Evolving vaccine technology, homeopathy, thermal imaging, and energy coherence are just a few fascinating lectures that will be available along with some great hands-on labs.

The AHVMA is an organization of which I am proud to be a part; we strive to affect economics, policies, and the lives of our patients and owners on a national level. We have wonderful resources, partners, and connections

AHVMA Journal • Volume 63 Summer 2021

encompassing the goals of the association. Our AVMA House of Delegates membership has been instrumental in promoting greater understanding of holistic medicine as a valid and recognized practice in the veterinary field. Since I personally opened my own holistic clinic over nine years ago, six other veterinary clinics in my little town have sent their doctors for acupuncture training and certification.

As the focus of both human and animal health shifts towards a more holistic mindset, I feel it is part of our collective responsibility to welcome more veterinarians into our “home.” There is so much more to learn, and I think most of that knowledge will be in energy medicine and the understanding of how quantum physics is to some extent the scientific explanation for it. The expansion of our medicine is infinite, and it is exciting to find out what new modalities we can learn at our Conferences and beyond.

Please help us encourage our colleagues to return or join us for the first time. Our holistic modalities have made us better history takers and diagnosticians and more patient in anticipating positive outcomes. It is an approach and an art that heals with new perspectives at every turn.

Colleen Smith, DVM

AHVMA President 2020-21

AHVMA Journal • Volume 63 Summer 2021

Scientific Review

Integrative Treatment of Canine Cognitive Dysfunction Janice L. Huntingford, DVM, MS

Author Contact: Essex Animal Hospital 355 Talbot St. North Essex, ON N8M 2W3, Canada Phone: (519) 776-7325 Email: drjanhuntingford@gmail.com

Abbreviations Aβ Amyloid-β AD Alzheimer’s disease CBD Cannabidiol CCD Canine cognitive dysfunction DISHAA Disorientation; social Interactions; S Sleep-wake cycles; House soiling, learning, and memory; A Activity; and Anxiety GBA Gut-brain axis MCT Medium-chain triglyceride SAMe S-adenosyl-L-methionine SCFA Short-chain fatty acid TCVM Traditional Chinese Veterinary Medicine

Abstract

Introduction

Canine cognitive dysfunction (CCD) has been called the canine analogue of human Alzheimer’s disease (AD). It is more common than previously believed and affects 14% to 35% of the pet dog population, with a prevalence of 14% to 68% in dogs older than 8 years of age. The hallmark of this disease is slowly progressive deterioration of cognitive abilities and behavioral changes. Confusion, anxiety, interruption of the sleep-wake cycle, and decreased interaction with the owner are common manifestations of this syndrome in dogs. The pathophysiology involves cerebral inflammation and vascular disease, deposition of amyloid plaques, oxidative brain injury, and mitochondrial dysfunction. There is no cure for CCD, but there are many proven therapeutic interventions available to the integrative practitioner, which have the best outcome when instituted early in the course of the disease. Dietary therapy, nutraceuticals, physical therapy, cognitive enrichment, acupuncture, and herbal therapy are all used to slow the progression of this neurodegenerative disease.

Canine cognitive dysfunction (CCD) is a common medical condition that occurs in dogs older than 8 years of age (1-3). It is akin to canine dementia and is considered the canine analogue of human Alzheimer’s disease (AD) (1-3, 8-11). The disorder is characterized by slow deterioration of cognitive abilities associated with altered mentation and dementia. In older dogs, this manifests as behavioral changes, such as disorientation, loss of house-training and other learned behaviors, changes in sleeping patterns, changed or altered interaction with family members and other pets, and alterations in anxiety and activity (1-7, 9). The acronym DISHAA, which stands for Disorientation; social Interactions; Sleep-wake cycles; House soiling, learning, and memory; Activity; and Anxiety, has been developed as a tool to help small-animal practitioners and pet owners with early diagnosis of this condition (1, 10). CCD begins much earlier in life than previously suspected, and veterinarians can play a key role in diagnosis and client education regarding early detection. Preventive measures should be considered when the dogs are

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middle-aged to ward off clinical signs and the effects of progressive cognitive decline (8). Integrative practitioners are often asked to treat these patients because conventional pharmaceuticals and interventions may not provide complete relief from this syndrome. Within the veterinary community, there are many misconceptions about CCD in regard to general pathophysiology, prevalence, treatment, and relevance of the disease. According to Dewey et al., the top 3 misconceptions about CCD are that normal canine aging causes mild cognitive impairment, CCD is uncommon, and there are no effective treatments (1). The purpose of this paper is to highlight the available literature and summarize the pathophysiology, characteristics, and available treatments for the integrative practitioner.

Prevalence and Pathophysiology of CCD and AD CCD is an age-related disorder that is similar to AD in humans and occurs in older dogs. It has been estimated that the prevalence of CCD is between 14% and 35% of the companion dog population (1-3, 7). It is unknown whether CCD is increasing in the pet dog population, although with dogs living longer, it is speculated that this is the case. Although Salvin and colleagues estimated the prevalence of CCD to be 14.2% in dogs older than 8 years of age, they also found that only 1.9% of the dogs had a previous CCD diagnosis from a veterinarian (7). It is therefore likely that veterinarians and clients are dismissing the signs of CCD as a function of normal canine aging (1-12). As with people with AD, the prevalence of CCD dramatically increases with age, with a recent study showing 28% of dogs 11 to 12 years of age and 68% of dogs 15 to 16 years of age suffering from CCD (1-10). Bain and coworkers found that 22% of the dogs in their study did not have clinical signs initially but developed them 12 to 18 months later, whereas 48% of the dogs with impairment in 1 category displayed impairment in 2 or more categories during the same time period (13). The pathophysiology of both CCD and AD involves brain vascular disease and the accumulation and aggregation of amyloid-β (Aβ) peptide. Aβ, a neurotoxic protein, accumulates as plaques in the forebrains of dogs with CCD and people with AD, where it causes neurodegeneration (1, 2, 8, 10, 11). However, dogs usually do not show the severe cognitive impairment seen in humans with AD (9). According to Dr. Elizabeth Head from the Center on Aging at the University of Kentucky, the severity of CCD is determined by the extent of Aβ deposition in the brain (12). The deposition of Aβ is a hallmark for both AD and CCD, making the canine the best naturally occurring animal model for studying human AD (1, 2, 9, 12, 14-16). The pathophysiology of CCD and AD is complex and multifactorial. Pathologic similarities exist between the

brains of people with AD and dogs with CCD (1, 2, 9, 15). Ventricular dilatation, meningeal thickening, gliosis, and cerebral vascular changes occur in both species (1, 11, 14). Decreased cerebral blood flow is an important facet of the pathogenesis of CCD (1, 2). Many of these changes have to do with cerebral vascular disease related to Aβ accumulation around blood vessels and in neurons. Several studies have shown that these proteins interfere with synaptic function because they are highly toxic (2, 11, 12, 14-16). In addition to these toxic Aβ proteins, some histological studies have shown an intraneuronal accumulation of hyperphosphorylated microtubularassociated proteins called tau proteins (17). These proteins are a precursor to neurofibrillary tangles, which are found in the brains of AD patients but not in CCD patients (1, 2, 11). It is postulated that canines do not live long enough to develop mature neurofibrillary tangles, but nevertheless, the development of tau protein indicates mitochondrial dysfunction (2, 9-12). There are many forms of CCD, and often they involve depletion of neurotransmitters or disruption of neuronal pathways. All cases of neurodegeneration and cognitive decline involve oxidative stress and mitochondrial dysfunction.

Mitochondrial dysfunction is central to the development and progression of AD and CCD (18-20). Mitochondria are responsible for producing adenosine triphosphate (ATP), the energy for all cellular functions. The mitochondria undergo functional and morphological changes (including gene expression), some of which is attributed to Aβ deposition. A mitochondrial-mediated impairment of autophagy potentiates Aβ deposition (1, 17). When the cell is unable to catabolize proteins due to defective mitochondria, proteins are deposited as plaques, and there is an intraneuronal accumulation of tau proteins. Tau proteins belong to a family of microtubular proteins located within the neurons (17, 18). During neurodegenerative diseases, tau proteins undergo hyperphosphorylation and accumulate within the neurons, interfering with neurotransmission. Normally, the mitochondria have the ability to decrease the toxic effect of Aβ on cellular function; however, this function diminishes as the mitochondria decline (1). The declining mitochondria have a decreased ability to generate cellular energy in the brain, and the neurons affected by AD and CDD have an impaired ability to uptake and use glucose (1, 17-19).

An imbalance of neurotransmitters in the brain has been documented in both AD and CCD. This imbalance may consist of damage and depletion of dopamine and altered cholinergic transmission, a disruption of the serotonergic pathway, AHVMA Journal • Volume 63 Summer 2021

noradrenergic transmitter disruption, and glutamatemediated excitotoxic neuronal damage (1, 2, 9, 11, 16, 17). Excessive stimulation of the glutamate receptors— that is, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors—contributes to neuronal excitotoxicity and death. Additionally, impairment of the function of inhibitory interneurons adds to the impaired neuronal network of AD and CCD patients (1, 2). Of all of these changes, cholinergic dysfunction has the highest and most consistent relationship to the development of CCD and AD. According to Dewey and colleagues, other abnormalities that are found consistently in the brains of AD and CCD patients include elevation of acetylcholinesterase, resulting in cholinergic decline; increase in monoamine oxidase (MOA) B, which catalyzes the breakdown of dopamine and allows free radicals to form; and elevated CSF levels of lactate, pyruvate, and potassium (1).

Astrocytes and microglia are the main immune cells in the CNS. Both of these cells function to reduce the production of Aβ and remove it before formation of senile plaques can occur. In early AD, large numbers of microglia accumulate to slow down the deposition of Aβ (1, 11, 12, 21). However, this deposition continues, suggesting that the ability of the microglia to clear Aβ declines with age. The failure of the microglia to perform their function appears to be a direct result of the Aβ-induced inflammatory response (21-23). Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine produced by the microglia that up-regulates Aβ production so the microglia, which were recruited to clean the Aβ protein from the brain, end up promoting the deposition of plaques (21). Astrocytes and microglia are responsible for uncontrolled neuroinflammation that is associated with the progression of both AD and CDD (22).

Involvement of the Gut-Brain Axis in Cognitive Dysfunction

The gut-brain axis (GBA) is an interactive network between the brain and the gut that is composed of neural, immunological, and endocrinological mediators. The GBA is mediated by the enteric nervous system, the CNS, and the intestinal microbiota. The vagal and spinal afferent nerves connect the gastrointestinal (GI) tract to the brain, and efferent sympathetic and parasympathetic fibers run from the brain to the GI tract (24-28). The main modulator of physiological stress is the hypothalamic-pituitary-adrenal (HPA) axis. The HPA also modulates alimentary function (24). Corticotrophin-releasing factor is released by the hypothalamus, affecting intestinal motility, permeability, and inflammation. Bacterial metabolites, such as shortchain fatty acids (SCFAs), GABA, and serotonin precursors, 12

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affect the brain via the enteric nervous system. These stimulate the sympathetic nervous system and affect learning and memory (27, 28).

In humans, neurodegenerative disorders such as AD have been linked to dysfunction of the GBA. A number of studies have shown a link between gut microbiome dysbiosis (as a result of antibiotic exposure, dietary change, or illness) and an aggregation of Aβ plaques in the intestinal and CNS cells (25-27). It has been suggested that the bacterial amyloid proteins overlap structurally with human Aβ proteins and induce a molecular mimicry, an immune response to self-antigens (in this case, cerebral Aβ proteins), which ultimately causes a greater inflammatory response in the brain to Aβ proteins due to altered gut microbiome (24). Alternatively, some species of bacteria have been shown to increase levels of SCFAs by digesting dietary fiber in the colon. SCFAs stimulate the release of serotonin from the sympathetic nervous system. Serotonin influences the CNS and has a positive effect on learning and memory (24, 28). When SCFAs are catabolized to ketone bodies, an alternative source of ATP is provided to the brain, which is helpful for patients with glucose dysmetabolism as the result of AD. Perhaps more importantly, studies have shown that low levels of SCFAs negatively affect the immune system and the function of the CNS and peripheral nervous system (24, 27). The gut microbiome of dogs is similar to that of humans, and it has been suggested that nutritional supplements may improve some of the cognitive symptoms in dogs with CCD, although further research is needed (28).

History, Clinical Signs, and Diagnosis

The typical CCD patient is a geriatric dog (older than 8 years of age) with a slowly progressive history of cognitive decline over several months. No association has been found with body size, breed, or sex (1, 2). Six main clinical features are apparent according to the DISHAA test (1, 10, 17):

1. D isorientation in home and yard 2. Changes in social interactions with human family members 3. Decline in house-training 4. A lterations in sleep-wake cycles 5. A lterations in activity levels 6. A lterations in anxiety levels

A dog must have signs of dysfunction in more than 1 category to be considered for a diagnosis of CCD. Dogs with only 1 category affected may have cognitive decline (10). Like humans with AD, dogs with CCD may show anxiety,

abnormal mentation, compulsive circling, absent or inappropriate response to visual stimuli, and resistance to even minimal restraint (2, 29, 30). Transient vestibular episodes and recent onset of seizure activity are seen in AD, and some veterinary neurologists believe these may also indicate CCD (2, 29, 30) (a). Some of these clinical signs can be seen in dogs with other neurological illnesses, such as brain tumors or geriatric vestibular disease, which can make the diagnosis difficult. Although the DISHAA test was developed to screen for CCD, it is still a diagnosis of exclusion (1, 10, 16, 17). Medical conditions must be ruled out in order to make a definitive diagnosis of CCD. These problems may include, but are not limited to, hyperadrenocorticism, parathyroid disorders, thyroid disorders, diabetes mellitus, chronic kidney disease, cancer, cardiovascular disease, incontinence, liver disease, musculoskeletal disease, dental disease, prostatic disease, sensory loss, intracranial neurological disease, and other painful conditions. MRI diagnosis for CCD is rarely done in dogs due to possible anesthesia complications, cost, and falsenegative results (1, 2). Sometimes dogs that have clinical signs of CCD will have a normal MRI, and conversely, dogs whose MRIs show an aging brain may have no signs of CCD.

A recent study using MRI showed that dogs with CCD had significantly smaller total hippocampal volumes compared with successfully aging control dogs (31). This knowledge may help in the diagnosis of CCD.

Behavioral problems that look like CCD may include generalized anxiety, separation anxiety, fear-related aggression, pain-related aggression, noise or storm phobias, lack of house-training, attention-seeking behaviors, and compulsive disorders (32). Often, there will be concurrent behavioral and medical illness because medical and cognitive disorders may exacerbate existing, previously undiagnosed behavior problems.

Treatment Overview

There is no known cure for CCD. Therapeutic approaches are multiple and varied and are aimed at improving cognitive function or delaying cognitive decline (1, 2, 17). It is important to remember that certain diseases may increase progression of CCD and AD by accelerating brain aging (33-37). Examples include diabetes, osteoarthritis, hypothyroidism and hyperthyroidism, obesity, Cushing’s disease, chronic kidney disease, periodontal disease,

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congestive heart failure, pancreatitis, cardiomyopathy, liver disease, seizures, stress, and chronic infection. Major disease is a significant risk factor for cognitive decline and progression of AD, and because many of these diseases are diseases of chronic inflammation, they contribute to brain aging and thus to the progression of CCD (10, 33-37). When treating diseases, it is important to consider the impact any drug or herb will have on the disease progression. For example, dogs with neuropathic pain receiving gabapentin could be switched to amantadine because it has similar effects (dopamine agonist) but also has positive benefits for CCD. Minocycline is also effective for neuropathic pain, and it reduces microglial inflammation (33, 38-40). Zonisamide and potassium bromide do not increase symptoms of CCD (33), but phenobarbital can have detrimental effects in AD patients. A small pilot study in dogs showed that antiepileptic drugs had no effect on CCD scores (41). This is surprising given that antiepileptic drugs, particularly phenobarbital, have been shown to increase AD in humans (42). Until more research is available, is it prudent to avoid antiepileptic drugs when treating epileptic dogs who have concurrent CCD. When anesthetizing CCD patients, the use of propofol is preferred to gas anesthesia and the use of glycopyrrolate to atropine (43). When possible, all drugs that increase cognitive decline should be removed from the patient and alternatives recommended. A partial list of drug classes to avoid would include barbiturates, benzodiazepines, anticholinergics, chemotherapeutic agents, isoxazoline parasiticides, corticosteroids, and gas anesthesia (33, 43-45). The pros and cons of using benzodiazepines in CCD and AD will be discussed in the next section. In humans, other conditions can worsen AD, and this is thought to be true of CCD. Lack of exercise, highcarbohydrate diets, excess calorie intake, obesity, and omega-3 and B vitamin deficiencies are thought to play a role in the progression of both AD and CCD (1, 2, 46-48).

Drugs

L-deprenyl, or selegiline, is the only FDA-approved veterinary drug in the United States for the treatment of CCD (17). Selegiline is a selective and irreversible inhibitor of MAO B. It may enhance dopamine and other catecholamines in the cortex and hippocampus and be neuroprotective, possibly by reducing free radical production and/or increasing enzymes that scavenge free radicals, such as superoxide dismutase and catalase (49). Existing studies show improvement in signs of cognitive dysfunction with selegiline, but there is some controversy because most of these studies are based on owner responses to questionnaires rather 14

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than standardized comparative cognitive testing (1, 50, 51). Some clinicians feel that the owner responses may not be based on true improvement in cognitive abilities but rather on the fact that selegiline increases brain catecholamines and this can produce nonspecific low-level hyperactivity (1). The recommended dose for selegiline is 0.5 to 1.0 mg/kg PO q 24 hours, generally given in the morning, particularly in dogs that have sleep pattern disturbances because it acts as a stimulant and may worsen agitation (49). There is variability in response, with most dogs responding within 2 weeks or slightly longer. In clinical trials, 77% of dogs had a favorable response within 30 days (50). The most improvement was seen in dogs that had disorientation and decreased interaction with family members. Dogs whose clinical signs were loss of house-training or changes in activity or in sleep-wake cycles showed the least improvement (50). Concurrent use with other MAO inhibitors (eg, amitraz, opioids, and tricyclic or other antidepressants) and SSRIs should be avoided because these drugs have the potential to cause serotonin syndrome. Reported adverse effects include restlessness and agitation, vomiting, disorientation, diarrhea, diminished hearing, increased destructive behavior in dogs with separation anxiety, anorexia, anemia, stiffness, and polydipsia. Some dogs may show increased signs of aggression (49). Selegiline is not an effective drug in human AD patients (1, 2).

Other drugs have been used to treat or improve CCD. NSAIDs may improve CCD by reducing brain inflammation (1). Amantadine, an NMDA receptor antagonist, has been shown to have benefits for AD in humans by enhancing the noradrenergic system (10, 52). Amantadine is currently used as an alternative to treating neuropathic pain in dogs, but studies on its efficacy for CCD are lacking. Minocycline reduces microglial inflammation and is neuroprotective in several models of animal neurogenerative diseases (33, 39, 40). It is also effective for neuropathic pain. Studies in CCD are also lacking for this drug. Some serotonergic drugs, such as trazodone or fluoxetine, may be used off label to treat some of the symptoms of CCD (1, 10, 17, 53). Benzodiazepines—in general, CNS depressants—have been shown to worsen signs of AD and increase cognitive loss because they promote neuroinflammation and can inhibit the signaling of the brain insulin receptor, thus decreasing uptake of glucose by the mitochondria (44, 45). Nevertheless, some clinicians have used them successfully on a shortterm basis for agitated dogs (10, 53, 54). They may also be used on a case-by-case basis to improve sleep in patients with altered sleep-wake cycles that do not respond to sleepinducing nutraceuticals, such as melatonin (54).

Other drugs used by veterinary behaviorists and other clinicians treating CCD include propentophylline, adrafinil, and nicergoline. Propentophylline has been used in Europe for older dogs with depression and lethargy. It increases blood flow to the brain and may have neuroprotective properties (10, 53, 54). Adrafinil enhances the noradrenergic system and may be useful in older dogs in maintenance of a normal sleep-wake cycle and to help improve alertness. However, safety and efficacy studies in the canine are lacking (10, 53, 54). Nicergoline, which acts on dopamine and serotonin receptors, is used to promote cerebral vasodilation and has been used in Europe to treat sleep disorders and diminished vigor in canines. However, it is not marketed in North America, and pharmacologic effects have not been published (54).

Diet and Nutraceuticals

In both human AD and CCD of dogs, diet and dietary supplements have a substantial impact on both the development and progression of cognitive decline (1, 3). High-carbohydrate diets, excessive calorie intake, hyperglycemia, obesity, omega-3 deficiencies, and B vitamin deficiencies will contribute to the progression of AD and CCD (46-48, 55, 56). Nutrients that are often deficient

in such individuals include B vitamins (eg, B12), vitamin C, vitamin E, mitochondrial cofactors (eg, L-carnitine, DL-α-lipoic acid), and carotenoids from green leafy vegetables. There are specific dietary recommendations for the prevention and treatment of AD. These include a diet rich in plant-based foods, soy protein, antioxidants, probiotics, omega-3 polyunsaturated fatty acids, whole grains, fruits, vegetables, nuts, foods enriched with medium-chain triglycerides (MCTs), and fish. The risk of cognitive decline in humans increases when red meats, poultry, refined sugar, processed food, and high-fat dairy products are added to the diet (1, 46). In the canine, diets high in processed carbohydrates and saturated fats can promote inflammation and increase the risk of cognitive decline (33). The addition of carotenoids and flavonoids as natural antioxidants from fruits, and particularly vegetables, has been associated with improvements in CCD (1, 2, 10, 17). These antioxidants are much more than just antioxidant in their actions. They can also act as mitochondrial cofactors and increase cellular endogenous antioxidant up-regulation (12, 18, 19). Fresh, balanced, homemade, less processed diets containing lean meats or fish and an abundance of fruits and vegetables are advantageous for dogs with CCD (1).

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Commercial diets for treatment and prevention of CCD are available (1, 48, 57). These diets are high in MCTs and have added carnitine, lipoic acid, long-chain omega-3 polyunsaturated fatty acids, vegetable-based carotenoids, vitamin E, and vitamin C (2, 3, 48, 57). Homemade diets that are low in high-glycemic carbohydrates and balanced with antioxidants and MCT oil seem to be effective. MCTs are recommended in dogs with CCD, either as part of a formulated diet or a supplement, for several reasons (1). The AD and CCD brain has an impaired ability to use glucose, the brain’s main energy source. MCTs provide an alternative energy source, in the form of ketone bodies, for the brain of cognitively impaired patients. MCTs are converted by the liver to the ketone body β-hydroxybutyrate for improved energy metabolism and mitochondrial function in the aging brain. These ketone bodies are rapidly converted to glucose precursors through interactions of astrocytes and glial cells with the surrounding neurons. Although this has been proven in humans, it may be suspect in dogs because, unlike humans, they do not generate ketones uniformly, and some other mechanism may be at work (1, 26). Dogs will generate some ketone bodies when supplemented with MCT oil but do not become ketotic (58). Nevertheless, supplementation with MCT improves learning and memory in aged dogs (10). It is thought that the MCTs may be involved in mitochondrial biogenesis and provide ketones locally to astrocytes for metabolism while not creating systemic ketosis (1, 2). MCTs also improve brain mitochondrial activity and decrease the level of brain amyloid precursor proteins (48). MCTs are commonly included in ketogenic diets for both people and dogs. In one study, a proprietary mix of MCTs was shown to improve cognitive function in aged Beagle dogs when incorporated into commercial food at 5% of the dry matter (48). Foods rich in MCTs are limited to only coconut and palm kernel oils. However, a nutraceutical MCT oil that is 100% MCT is recommended because coconut and palm kernel oil themselves may not contain therapeutic amounts. Proponents of these oils suggest using them at approximately 5% of the dry matter in the diet, initially as top dressing on a commercial food or by using coconut oil as a fat source in a properly formulated homeprepared diet. This amount of coconut or MCT oil should provide between 10% and 5% of the caloric content of the diet, respectively; however, the additional oil can create imbalances in the diet or diarrhea, particularly if extra treats are being given. Total calories are important to consider when adding MCT oil (1). Nutraceuticals have been used to treat both CCD and AD. Oral S-adenosyl-L-methionine (SAMe) was shown to be effective in improving mood and cognitive dysfunction 16

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in AD patients (59). One canine study showed that SAMe improved the signs of age-related dementia in 41% of dogs older than 8 years of age (60). Mitochondrial dysfunction, a known cause of CCD and AD, is often associated with pore opening in the mitochondrial outer membrane, known as the mitochondrial permeability transition port. Supplements or drugs that close the pore are highly effective in reducing mitochondrial damage and cell death and can reduce neurodegeneration. Apoaequorin is a supplement derived from jellyfish that acts as a mitochondrial permeability transition pore blocker and has been used to treat both AD and CCD (1, 10, 61).

Other nutraceuticals that have been used to treat both CCD and AD include omega-3 fatty acids, particularly docosahexaenoic acid (DHA), valerian root (Valeriana officinalis), resveratrol, melatonin, and gingko (Ginkgo biloba) (10, 54, 62). Some of these may have the effect of normalizing the sleep-wake cycle and decreasing anxiety. Several supplemental products that contain many of these ingredients have been researched. These include Senilife® (b), Novifit® (c), and Aktivait® (d).

Senilife® is a supplement containing a unique blend of antioxidants (phosphatidylserine, pyridoxine, gingko extract, resveratrol, and d-α-tocopherol) that work together to help reduce brain-aging behaviors in as little as 7 days according to Ceva Animal Health. Novifit® contains only SAMe tosylate disulfate. Aktivait® contains DHA and eicosapentaenoic acid (EPA), L-carnitine, vitamin C, N-acetyl-cysteine, α-lipoic acid, vitamin E, acetyl-Lcarnitine, coenzyme Q10, and phosphatidylserine.

Cannabis and AD and CCD

According to Kogan and colleagues, pet owners that have been using cannabidiol (CBD) and hemp extracts to treat anxiety in their dogs and cats have been pleased with the results and feel this treatment is effective (63). CBD affects both GABA and serotonin receptors and has been shown to have anxiolytic properties (64). A review by Maroon and Bost discussed the neuroprotective benefits of CBD, which include decreasing the production of inflammatory cytokines, influencing microglial cells to return to a ramified state, preserving cerebral circulation during ischemic events, and reducing vascular changes and neuroinflammation (65). CBD has been shown to reverse or prevent the development of cognitive defects in a mouse model of AD (66). Other studies show that a combination of tetrahydrocannabinol (THC) and CBD in a full-spectrum product reduced memory impairment in AD mice. In other murine studies, cannabinoids were found to reduce oxidative stress, microglial activation,

and neuroinflammation; facilitate removal of Aβ plaques and reduce their production; and decrease tau protein aggregation (66). Cannabinoids have been used in humans to reduce the signs of dementia in AD patients. Caregivers report decreased distress, agitation, and aggression and improvement in mood, appetite, and sleep quality in AD patients taking cannabis oil (67). Because CCD is a model for AD, this would suggest that cannabinoids may work in a similar way in canine patients. However, there are no published studies or evidence that cannabinoids such as CBD are effective in CCD, and further investigation is needed to determine its efficacy. Although CBD seems to be the most discussed, other cannabinoids, such as cannabigerol (CBG), cannabidiolic acid (CBDA), and tetrahydrocannabinolic acid (THCA), may play a greater role in neuroprotection. A full-spectrum product containing all the cannabinoids is being researched and may be the most successful in treating canine patients (e).

Cognitive Enrichment and Physical Therapy

Regular exercise, social interaction, new toys, and increased stimulation have been shown to improve cognitive dysfunction in older dogs (10, 16, 17, 68, 69). Socialization classes for older dogs that include basic obedience, scent discrimination tasks, and obstacle courses target balance, proprioception, and cognitive skills (68, 69). Owners can be taught to challenge their dogs at home with hide-and-seek games, puzzle toys, and other physical interactions to work on mental stimulation as a preventive and a therapy for CCD (10, 17, 69). Physical activity might be a useful strategy in therapeutic management by delaying loss of neuromusculoskeletal functioning and the usual complications of dementia. Regular exercise should be promoted by veterinarians for all dogs, especially those that are aged (68-70). There is an inverse relationship between physical activity and Aß protein deposits in the brains of mice (71). If this is also true of dogs, exercise becomes even more critical for dogs showing early signs of CCD. Specialized exercise programs can be designed to safely exercise dogs after individual physiotherapy assessments are completed and other orthopedic, neurological, or medical problems are taken into account (68, 69). Swimming or underwater treadmill walking, for example, could be great modes of exercise that do not impart the same concussive forces on potentially arthritic joints of older animals (68-70).

Chinese Herbs and Acupuncture

In Traditional Chinese Veterinary Medicine (TCVM), CCD is manifested by the loss of Shen. An animal with a healthy Shen will be alert, responsive to the environment, and exhibit normal behavior. When the Shen is lost, the results

are poor memory, disorientation, confusion, anxiety, and hyperactivity. According to Xie, 2 common TCVM patterns with similar clinical signs have emerged in CCD:

1. Phlegm Misting the Mind with Heart and Spleen Qi Deficiency 2. H eart Yin and Blood Deficiency along with Brain Blood Stasis (72)

Although clinical signs of the 2 syndromes are similar, a patient with the first syndrome has a pale, wet tongue and deep pulse that is weaker on the right side. A patient with the second syndrome has a dry red or pale tongue and deep pulse that is weaker on the left side (72).

A third pattern, which is also seen in patients with AD and in many dogs with CCD, is one of Kidney Qi and Essence Deficiency leading to Kidney Yin and later Kidney Yang Deficiency (73). Maciocia states that the Marrow is transformation of the Jing from Kidneys, and it impacts the brain, spinal cord, and bone marrow; the brain is called the Sea of Marrow, and when it is full, the brain is healthy, but when there is a deficiency, signs of dementia may occur (74). TCVM would treat these syndromes with herbal formulas, food therapy, and acupuncture. Treatments can be extensive, but most will focus on treating Phlegm, Blood Stasis, and supporting the Kidney. Table 1 summarizes common veterinary formulas used for treating CCD in dogs depending on the TCVM pattern. Table 2 lists Chinese formulas used in AD, and Table 3 lists Chinese food therapy that could be considered for dogs with CCD. (See Tables on pp. 18-19.)

Some combination formulas, such as Liu Wei Di Huang (Table 1), have been used for treatment of AD as well. Sai Luo Tong formula, not a commonly used veterinary formula, consists of the bioactive components extracted from ginseng (Panax ginseng), ginkgo, and saffron (Crocus sativa) and has been shown to cause significant improvement in neurocognitive function, learning, and memory in AD patients (2, 75). Other Chinese herbal formulas that have been researched for use in AD, such as Ba Wei Di Huang Wan (Table 1), Fu Fang Dan Shen, and Yi Gan San (Table 2), have also shown encouraging data on treating cognitive and psychological symptoms in patients with dementia (1, 76).

Acupuncture, particularly electroacupuncture, may be beneficial in treating patients with CCD. It should be performed once weekly for 3 to 5 treatments, and then the treatments may be spaced out according to need. In this author’s experience, treatments may last 1 to 4 weeks depending on the severity of the dysfunction (72). AHVMA Journal • Volume 63 Summer 2021

Table 1: Common Veterinary Formulas Used for Treating CCD TCVM Formula Ingredients Classical Antecedent

TCVM Pattern Treated

Angelica (Bai Zhi) Pinellia (Ban Xia) Ligusticum (Chuan Xiong) Salvia (Dan Shen) Ligusticum (Gao Ben) Phlegm Misting the Mind, Stasis in the Mansion of Nao Yu Fang Pueraria (Ge Gen) with Heart and Spleen Qi Deficiency the Mind (e) Carthamus (Hong Hua) Bombyx (Jiang Can) Scorpion (Quan Xie) Cimcifuga (Sheng Ma) Fritillaria (Zhe Bei Mu) Paeonia (Bai Shao Yao) Biota (Bai Zi Ren) Bupleurum (Chai Hu) Salvia (Dan Shen) Angelica (Dan Gui) Poria (Fu Shen) Ophiopogon (Mai Men Dong) Heart Yin and Blood Deficiency Ostrea (Mu Li) Tian Wang Bu Xin Dan Shen Calmer (e) with Brain Blood Stagnation Citrus (Qing Pi) Zizyphus (Suan Zao Ren) Asparagus (Tian Men Dong) Schisandra (Wu Wei Zi) Cyperus (Xiang Fu) Scrophularia (Xuan Shen) Polygonum (Ye Jiao Teng) Polygala (Yuan Zhi) Rehmannia root (Sheng Di Huang) Chinese yam (Shan Yao) Cornus fruit (Shan Zu Yu) Jin Gui Shen Qi Wan Kidney Qi Deficiency, Poria (Fu Ling) Bai Wei Di Huang Wan (Rehmannia Eight)* Dampness Accumulation Alisma tuber (Ze Xie) Moutan bark (Mu Dan Pi) Cinnamon twig (Gui Zhi) Prepared aconite (Fu Zhi) Ginseng root (Ren Shen) White atractylodes (Bai Zhu) Poria (Fu Ling) Phlegm Misting the Mind, Pinellia rhizome (Fa Ban Xia) Liu Jun Zi Tang Liu Jun Zi Tang with Heart and Spleen Qi Deficiency Jujube fruit (Da Zao) (Six Gentlemen) Tangerine peel (Chen Pi) Licorice root processed (Gan Cao Mi) Fresh ginger root rhizome (Sheng Jiang) Mantis egg casing (Sang Piao Xiao) Fossilized bone (Long Gu) Panax ginseng root (Ren Shen) San Piao Xiao San Kidney Qi Deficiency and Heart Qi Poria (Fu Ling) (Mantis Egg-Case San Piao Xiao San Deficiency Acorus (Shi Chang Pu) **, *** Combination) Polygala (Yuan Zhi) Turtle shell (Gui Ban) Chinese angelica (Dang Gui Shen) Rehmannia root (Shu Di Huang) Cornus fruit (Shan Zhu Yu) Kidney Qi and Yin Deficiency Chinese yam (Shan Yao) Liu Wei Di Huang*** Liu Wei Di Huang and Heart Yin Deficiency Water plantain rhizome (Ze Xie) Poria (Fu Ling) Tree peony bark (Mu Dan Pi) * Used in humans for AD as well. ** Turtle shell is replaced with oyster shell by most manufacturers. *** Used for AD. Abbreviations: AD, Alzheimer’s disease; CCD, canine cognitive dysfunction; TCVM, Traditional Chinese Veterinary Medicine.

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Action of Formula

Moves Blood to break down Stasis in the brain and transforms Phlegm

Nourishes Heart Yin and Blood, calms Shen, and soothes Liver Qi

Tonifies Kidney Qi

Tonifies Spleen Qi, transforms Dampness, expels Phlegm, and descends Stomach Qi

Tonifies Heart and Kidney Qi and stabilizes Jing

Tonifies Kidney Yin Deficiency and Heart Yin Deficiency

Effective acupuncture points have included Yin Tang, LI20, GV20, GV14, ST36, HT7, PC6, CV6, CV12, CV17, SP10, LI4, and LIV3 (1, 72). Table 4 summarizes treatments for CCD.

Summary

CCD is a common neurogenerative disease of aged dogs akin to canine dementia and is considered to be the canine analogue of human AD. It is important for veterinarians to recognize that CCD is not a part of normal aging, and the processes that lead to symptoms of CCD begin much earTable 2: Constituents of Chinese Herbal Formulas Used in AD Formula Name Ingredients Fu Fang Dan Shen

Yi Gan San

Chinese salvia root (Dan Shen) Notoginseng root (San Qi) Oriental sweet gum resin (Shu He Xiang) Atractylodes (Chao Bai Zhu) Poria (Fu Ling) Angelica (Dang Gui) Sichuan lovage (Chuan Xiong) Cat’s claw (Gou Teng) Bupleurum (Chai Hu) Licorice (Gan Cao)

lier in life. For this reason, veterinarians should consider preventive measures when the dogs are middle-aged to ward off clinical signs and the effects of progressive cognitive decline. Proactively, clinicians could use the DISHAA tool on all canine patients that are 6 years of age and older. Diagnosis of CCD relies on a high index of suspicion by veterinarians and asking the right questions. Therapeutic interventions include dietary modification, nutraceuticals, physical therapy, and cognitive enrichment. Acupuncture and herbal therapy also have a place in the treatment of this complex disease. The key to successful treatment of CCD is multimodal therapy. Table 3: Common Foods Used for Chinese Food Therapy for AD and CCD (74) Condition/Organ Treated Recommended Foods Black mushrooms, pears, lotus root, carrots, peas, bamboo shoots, lean pork or fish Lamb, goat, deer, ginger, soybeans, pumpkin, broad beans Celery, spinach, coriander, bok choy, Chinese cabbage, green leafy vegetables; reduce grains

Nourish Yin Tonify Yang Resolve Phlegm Weak or Emaciated

Bone broth, chicken soup, eggs, fish

Heart

Vegetables, fruit, asparagus Lean beef, brown rice; avoid greasy, cold, or sour foods Soybeans, pork; avoid pungent foods and excess sweets

Spleen Kidney

Table 4: Summary of Treatments for CCD Diet Mild cognitive dysfunction

Homemade with MCT or commercial preparation; calorie restriction; veggies and fruits

Drugs

Selegiline

Nutraceuticals Fish oil and antioxidants; melatonin; B vitamins; apoaequorin; Senilife®, Novofit®, or Aktivait®

Selegiline; SSRIs; Fish oil and antioxidants; other drugs melatonin; B vitamins; as needed for Moderate to severe apoaequorin; SAMe; Senilife®, sleep-wake cycle, cognitive dysfunction Novofit®, or Aktivait® aggression, or other clinical signs Abbreviations: CBD, cannabidiol; MCT, medium-chain triglyceride; SAMe, S-adenosyl-L-methionine. Homemade with MCT or commercial diet; calorie restriction; veggies and fruits

Exercise/Mental Stimulation

Herbs

½ hour of walking and swimming, followed by ½ hour of interactive play, puzzles, and brushing and combing

Gingko; green tea (Camellia sinensis); turmeric (Curcuma longa); Rehmannia 6; full-spectrum CBD

Weekly for 3-5 treatments and then weekly or prn

½ hour of walking and swimming, followed by ½ hour of interactive play, puzzles, nose work, and brushing and combing

Chinese herbs depending on pattern; gingko; green tea; turmeric; full-spectrum CBD

Weekly to every other week

Acupuncture

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Endnotes a. Personal communication by email with Curtis W. Dewey, DVM, MS, Associate Professor, Section of Neurology, Cornell University College of Veterinary Medicine, Ithaca, NY, April 7, 2021 b. Senilife®, Ceva Animal Health, Lenexa, KS 66215

c. Novifit ®, Virbac Corporation, Fort Worth, TX 76137

d. Aktivait ®, VetPlus Global LTD Animal House, Lytham St Annes, Lancashire, United Kingdom

e. Personal communication by email with Joseph J. Wakshlag, DVM, PhD, Chief Veterinary Medical Officer, Ellevet Sciences, South Portland, ME, January 6, 2021 f. Dr. Xie’s Jing Tang Herbal Inc., Ocala, FL 34482

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40. Parachikova A, Vasilevko V, Cribbs DH, LaFerla FM, Green KN. Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation. J Alzheimers Dis. 2010;21(2):527-542. doi: 10.3233/JAD-2010-100204 41. Winter J, Packer RMA, Volk HA. Preliminary assessment of cognitive impairments in canine idiopathic epilepsy. Vet Rec. 2018;182(22):633-633. doi:10.1136/vr.104603

42. Cumbo E, Ligori LD. Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer’s disease. Epilepsy Behav. 2010;17(4):461-466. doi:10.1016/ j.yebeh.2010.01.015

43. Baetge CL, Matthews NS. Anesthesia and analgesia for geriatric veterinary patients. Vet Clin North Am Small Anim Pract. 2012;42(4):643-653, v. doi:10.1016/j.cvsm.2012.05.001 44. Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry. 2005;66(Suppl. 2):9-13.

45. Salzman C. Do benzodiazepines cause Alzheimer’s disease? Am J Psychiatry. 2020:177(6):476-478. doi:10.1176/ appi.ajp.2020.20040375 46. Solfrizzi V, Custodero C, Lozupone M, et al. Relationships of dietary patterns, foods, and micro-and macronutrients with Alzheimer’s disease and late-life cognitive disorders: a systematic review. J Alzheimers Dis. 2017;59(3):815-849. doi:10.3233/ JAD-170248

47. Pan Y, Kennedy AD, Jönsson TJ, Milgram NW. Cognitive enhancement in old dogs from dietary supplementation with a nutrient blend containing arginine, antioxidants, B vitamins and fish oil. Br J Nutr. 2018;119(3):349-358. doi:10.1017/ S0007114517003464 48. Pan Y, Landsberg G, Mougeot I, et al. Efficacy of a therapeutic diet on dogs with signs of cognitive dysfunction syndrome (CDS): a prospective double blinded placebo controlled clinical study. Front Nutr. 2018;5:127. doi:10.3389/fnut.2018.00127

49. Landsberg G. Therapeutic options for cognitive decline in senior pets. J Am Anim Hosp Assoc. 2006;42(6):407-413. doi: 10.5326/0420407

50. Campbell S, Trettien A, Kozan B. A noncomparative openlabel study evaluating the effect of selegiline hydrochloride in a clinical setting. Vet Ther. 2001;2(1):24-39. AHVMA Journal • Volume 63 Summer 2021

51. Milgram NW, Ivy GO, Head E, et al. The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog. Neurochem Res. 1993;18(12):1211-1219. doi:10.1007/BF00975038

52. Beata C, Beaumont-Graff E, Diaz C, et al. Effects of alphacasozepine (Zylkene) versus selegiline hydrochloride (Selgian, Anipryl) on anxiety disorders in dogs. J Vet Behav. 2007;2(5): 175-183. doi:10.1016/j.jveb.2007.08.001

53. Landsberg G. Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(3):471-479. doi:10.1016/ j.pnpbp.2004.12.012 54. Landsberg GM, Deporter T, Araujo JA. Clinical signs and management of anxiety, sleeplessness, and cognitive dysfunction in the senior pet. Vet Clin North Am Small Anim Pract. 2011;41(3):565-590. doi:10.1016/j.cvsm.2011.03.017

55. Joseph JA, Shukitt-Hale B, Denisova NA, et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. J Neurosci. 1998;18(19): 8047-8055. doi:10.1523/JNEUROSCI.18-19-08047.1998

56. Barberger-Gateau P, Raffaitin C, Letenneur L, et al. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology. 2007;69(20):1921-1930. doi:10.1212/ 01.wnl.0000278116.37320.52

57. Pan Y, Larson B, Araujo JA, et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr. 2010;103(12):1746-1754. doi:1t 0.1017/ S0007114510000097

58. Berk BA, Law TH, Packer RMA, et al. A multicenter randomized controlled trial of medium‐chain triglyceride dietary supplementation on epilepsy in dogs. J Vet Intern Med. 2020;34(3): 1248-1259. doi:10.1111/jvim.15756

59. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994;48(2):137-152. doi:10.2165/00003495-199448020-00002

60. Rème CA, Dramard V, Kern L, Hofmans J, Halsberghe C, Mombiela DV. Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial. Vet Ther. 2008;9(2):69-82. 61. Moran DL, Underwood MY, Gabourie TA, Lerner KC. Effects of a supplement containing apoaequorin on verbal learning in older adults in the community. Adv Mind Body Med. 2016;30(1):4-11.

62. Hu J, Lin T, Gao Y, et al. The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. PLoS One. 2015;10(1):e0115973. doi:10.1371/journal.pone.0115973 63. Kogan LR, Hellyer PW, Robinson NG. Consumers’ perceptions of hemp products for animals. J Am Holist Vet Med Assoc. 2016;42:40-48.

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64. Richter, G. Cannabidiol in veterinary medicine. J Am Holist Vet Med Assoc. 2020;58(spring):46-53.

65. Maroon J, Bost J. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int. 2018;9(1):91. doi:10.4103/ sni.sni_45_18 66. Watt G, Karl T. In vivo evidence for therapeutic properties of cannabidiol (CBD) for Alzheimer’s disease. Front Pharmacol. 2017;8:20. doi:10.3389/fphar.2017.00020

67. Ahmed A, van der Marck MA, van den Elsen G, Olde Rikkert M. Cannabinoids in late‐onset Alzheimer’s disease. Clin Pharmacol Ther. 2015;97(6):597-606. doi:10.1002/cpt.117

68. Huntingford JL, Bale J. Therapeutic exercises Part 1: Land exercises. In: Tomlinson JE, Goldberg ME, eds. Physical rehabilitation for veterinary technicians and nurses. WileyBlackwell; 2017:286-307. 69. Goldberg ME, Tomlinson JE. The disabled patient Part 3: Special considerations for geriatrics. In: Goldberg ME, Tomlinson JE, eds. Physical rehabilitation for veterinary technicians and nurses. Wiley-Blackwell; 2017:187-204.

70. Edge-Hughes L, Cafci C, Campos AR. Canine cognitive dysfunction/dementia. Canine Fitness website. https://tinyurl.com/ CCDdementia. Published 2011. Accessed January 10, 2021. 71. Nelson R. Exercise could prevent cerebral changes associated with AD. Lancet Neurol. 2005;4(5):275. doi:10.1016/ S1474-4422(05)70064-8

72. Xie H. How I treat cognitive dysfunction syndrome. In: Xie H, Chrisman C, Trevisanello L, eds. Traditional Chinese veterinary medicine for neurological diseases. Proceedings of the 13th Annual International TCVM Conference. Jing Tang Publishing; 2011:113-116.

73. Marsden S. Formulas for behavioral disorders. In: Dr. Steve Marsden’s essential guide to Chinese herbal formulas. College of Integrative Veterinary Therapies; 2014:190-191.

74. Maciocia G. Geriatrics. The Three Treasures News website. https://tinyurl.com/3TreasuresGeriatrics.

75. Zhang Y, Liu J, Yao M, et al. Sailuotong capsule prevents the cerebral ischaemia-induced neuroinflammation and impairment of recognition memory through inhibition of LCN2 expression. Oxid Med Cell Longev. 2019:8416105. doi:10.1155/2019/8416105

76. Iwasaki K, Kobayashi S, Chimura Y, et al. A randomized double-blind, placebo-controlled clinical trial of the Chinese herbal medicine “ba wei di huang wan” in the treatment of dementia. J Am Geriatr Soc. 2004;52(9):1518-1521. doi:10.1111/ j.1532-5415.2004.52415.x

Scientific Review

Acupuncture for the Treatment of Neuromuscular Conditions in Dogs and Cats, with Emphasis on Intervertebral Disc Disease Bonnie D. Wright, DVM

Author Contact: MistralVet Consulting 4450 Thompson Parkway, Johnstown, CO 80534 970-699-8790 www.mistralvet.com

Abbreviations

Abstract

conditions (1). Despite the deficits in research, there is growing use and appreciation of acupuncture in veterinary medicine, and species-relevant data for the use of acupuncture in dogs is present for spinal cord diseases (2-5).

The effect of acupuncture needling on tissues creates local and remote biochemical and biomechanical changes. All points (both verum and sham) will interact with fascia, causing mechanotransduction in fibroblasts and other cell types. All points neuromodulate and will also modify fluid motion and immune balance via lymphatics. Effects that are more specific to particular points include location and distribution of neuromodulation, degree of immune modulation, muscle or trigger point effects, brain or homeostatic changes, sympathetic and parasympathetic stimulation, remote visceral organ effects, and degree of lymphatic flow modulation. These distinctive effects help to separate the effects of verum and sham acupuncture points and contribute to the diversity of acupuncture effects and complexity of research on acupuncture. Frequently selected acupuncture points for various conditions, such as intervertebral disk disease, have common and distinguishing physiological characteristics. The coincident choosing of these points could be justified from either a viewpoint of traditional Chinese medical acupuncture or one of Western medical acupuncture (WMA).

Introduction

In veterinary species, acupuncture studies that contain randomized, controlled clinical trials are lacking for most

DRG ECM Estim HJ TCVM WMA

Dorsal root ganglion Extracellular matrix Electrical muscle stimulation Hwato Jiaji points Traditional Chinese Veterinary Medicine Western Medical Acupuncture

In contrast to the dearth of clinical trials, acupuncture has a vast database of physiological studies that explore its local, regional, and systemic effects. Both needle-based and location-based associated techniques such as laser and aquapuncture are included (6-8). Deeply reliant on neurophysiology, this acupuncture research helps to inform the clinical practice of acupuncture, but a vast distance can exist between the neurophysiological science and actual practice. Relating these physiological mechanisms to the clinical practice of acupuncture is a moving target, but critical in order to both broaden the understanding of acupuncture mechanisms and to translate them to specific treatment concepts. This is the charge of this scientific review.

All acupuncture points share some physiological effects, whether verum points (described in acupuncture texts) or other points (often referred to as sham) (9). Distinct points, often those frequently described in acupuncture textbooks and associated with specific observed effects, will also contribute unique physiological effects (9). The shared effects include interaction with fascia, mechanotransduction in fibroblasts and other cell types, neuromodulation AHVMA Journal • Volume 63 Summer 2021

toward analgesia, modulation of fluid motion, and axonreflex–mediated modification of the microvascular environment (10-12). Effects that may be more specific to certain points compared to others include location and distribution of neuromodulatory changes, degree of immune modulation, muscle or trigger point effects, brain or homeostatic changes, sympathetic and parasympathetic effects, remote visceral organ effects, and degree of lymphatic flow modulation (9, 13-16).

Interaction with Fascia and Mechanotransduction

Implicit in every acupuncture needle placement is the movement and structural manipulation of the cells and extracellular matrix at the tip of the needle (10). This aspect of needling is amplified with needle manipulation and the sensation of deqi, which is a sensory sensation at the tip of the needle that coincides with the feeling of “grab” on the needle due to contraction of fascia and fibroblasts (17). When tissue is mechanically altered (tissue deformation), growth factors and a variety of proteins and neurotransmitters are released, leading to changes in pain processing, metabolic processes, inflammation, blood flow, and healing capacity (10).

Mechanotransduction refers to the processes through which cells sense and respond to mechanical stimuli by converting them to biochemical signals that elicit specific cellular responses (18). Cells are adjacent to either other cells or to extracellular matrix (ECM). The ECM is composed of a variety of proteoglycans and elastic and collagen fibers. Many of these compounds, and the collagen itself, are made by local tissue fibroblasts which are physically and functionally tied into the collagen network, fascia, and ECM. In addition to the fibroblasts managing the ECM tension in diverse regions, other cells in each region change in function and genetic expression as the ECM tension changes. Changes in ECM composition and tension/ compliance relate to the progression of degenerative conditions, tumor progression or metastasis, and aging in general (19). As a familiar example, consider the increased rigidity seen in cardiac disease in response to increased chamber pressures (18). Broadly considered, mechanotransduction is integral to the effect of placing an acupuncture needle (20). While the eventual modification of adjacent nerve fibers leading to neuromodulation is indisputable, there are 2 decades of physiological research showing the importance of the collagen and ECM matrix in transmittal of the mechanical signal from an acupuncture needle to the nervous system (7, 10, 21). Fascial structures are ubiquitous throughout the body. Treating acupuncture points at a superficial 24

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depth may provide input to microvascular structures or, with deeper needling, may provide input to deeper fascial sheets. These deep myofascial structures perform neuromuscular feedback loops and provide structural support, which can be modified with sufficient penetration of the acupuncture needle (22).

Neuromodulation: Peripheral, Central, and Corridor Structrures

With tissue mechanotransduction there is also inevitable traction and modulation of the nervous system (20). Neuromodulation alters neurotransmitters at the skin, along axons, in the spinal cord, interneurons, brain, and even in the supportive structures of the glia. These changes can be short-term, immediately improving comfort and function, or they can be long-standing or permanent, utilizing the plasticity of the nervous system to result in structural differences in pain processing and nerve function (23). Neuromodulation is intrinsic to the analgesic actions of physical medicine techniques in general, and particularly to the practice of acupuncture (24).

The most superficial layers of sensation are primarily occupied by pain (A-d and c fibers) and transient receptor potential (TRP) channel modified high-threshold receptors (8). Touch sensation occurs at the transitional layers, while the hypodermal layer carries vibration, pressure, and stretch as well as the origins of the lymphatics, which are the waterways of the body. Sensation has different underpinnings in haired and non-haired (glabrous) skin, and some of these variations help to explain why very distal points are described as having alternate indications. Non-haired regions and distal regions may have different physiologic consequences when compared to points over haired skin. Gentle touch receptors in mammalian skin collaborate with other sensory components to provide the sensory input from an acupuncture needle (25). The depth of needle placement has superficial effects via mechanotransduction. With deeper penetration there is also interaction with different tissues and innervation patterns. (22). Other neurosensory structures exist that are deep to the skin but outside the spinal cord region. These include muscle spindle organs, golgi tendon organs, and the dorsal root ganglion (DRG). Like cutaneous sensory sensation, golgi tendon and muscle spindle sensory tissues integrate with spinal and central reflex loops as well as convey pain information to the brain (26). These reflex loops contain afferent sensory information and result in reflex modulation of pain, muscle tension, and coordination of muscle and tendon groups to generate kinesthetic activity. Direct effects on motor units are a component of acupuncture

treatment and can be utilized to neuromodulate injured or dysfunctional motor reflexes (27, 28). This commonly targeted benefit of acupuncture is also shared by techniques known as dry needling, performed by physical therapists and acupuncturists, when targeting pathologically shortened muscle groups known as myofascial trigger points (29, 30). Several named acupuncture points exist over motor units that can contain sensory motor fibers. The sensation of needling these regions is characterized by cramping type pain, and much of this signal is carried via Aα and Aγ nerve fibers. Myofascial trigger points can also occur in motor regions that are not verum acupuncture points but that also benefit from treatment and are identified as Ah Shi (painful) points (30). The DRG cell body cell body is part of the peripheral nerve and manages the receptor populations, microtubular arrays, and ion channel representation in the peripheral nerve. The nerve cell body is integrally involved in the signals ascending from the peripheral tissues to the spinal cord. An important contribution to the analgesia effects of acupuncture is made by purines, released at the peripheral tissue during acupuncture needle stimulation. These neurotransmitters create transcriptional changes at the nerve cell body in the DRG, resulting in modification of the pain signals at the level of the axon distal to the DRG (31).

to decrease central pain amplification. Pain sensation can be modified by the local neurochemical milieu and also by descending input from the midbrain. Acupuncture has also been shown to aid in the modification of descending inhibitory mechanisms, and this method of testing the nervous system may significantly improve the clinical data available to demonstrate acupuncture efficacy (34). In the dorsal horn and infusing all structures within the blood-brain barrier (comprised of astrocytes) are glia. Glia invest each synapse and participate in the synaptic activity. The glia act as the structural and inflammatory cells of the nervous system. They are involved in sleep, mood, pain amplification, pain suppression, tolerance, and addiction. Acupuncture has been shown to influence the activity of glia, potentially reversing some of the negative effects of glial stimulators (like opioids) and decreasing the long-term central neuroinflammation resulting from pain and opioid treatments (23). The somatotropic layout of the spinal cord is integral to the ability of acupuncture to modify deep tissues and organs. Deeper tissues can be modified by interacting with

The dorsal horn of the spinal cord is the receiving zone for afferent impulses ascending from the periphery. Significant diversity of receptors, pain fibers, and neurochemical compounds contribute to the magnitude and type of signal seen at the dorsal horn. At this level, the signal can be transduced to nerve tracts that ascend to the CNS, with vast opportunity for modification here as well (32). At the dorsal horn, a variety of biochemicals can modify the likelihood that the signal will cross the synapse and create an action potential in the second order nerve. Momentto-moment modulation occurs through changes in GABA, serotonin, norepinephrine, nuclear factor kappa-b, calcitonin gene-related peptide, substance P, endorphins, and cannabinoids (33). Acupuncture effects emanating from the periphery have been shown to exert at least some modification on each of these compounds in various laboratory studies (14). In addition to the modifications possible at the first synapse, the topography of the spinal cord provides for interneurons that can inhibit or amplify the incoming afferent signal. Concepts such as diffuse noxious inhibitory control are being utilized to assess amplified pain states and to identify therapies such as acupuncture that work

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somatic sites that share the same spinal innervation network. Examples of this in modern medicine include “sea bands” for nausea (over acupuncture point PC6) and electrical stimulation over the tibial nerve (acupuncture point KI3) to improve urinary continence (35). This structural relationship creates a nervous system interaction that explains the peripheral or somatic recognition of visceral pain, such as myocardial infarction pain that is sensed in the left arm in men or the mandible in women. Likewise, the treatment of visceral structures through somatic sites is possible by targeting the nerve structures present in the inner Bladder line fascial plane (36).

Modification of autonomic outflow is most likely to occur near accessible portions of the sympathetic chain and parasympathetic ganglia. Examples of sympathetic proximity include the cervicothoracic junction (the start of the sympathetic chain) and the lumbosacral junction (the sacral sympathetic outflow). Examples of parasympathetic ganglia can be found in the thoracolumbar region (stellate ganglion) and at the thoracic inlet (cranial cervical ganglion). In addition to the modification of autonomic function via the vagal nerve, acupuncture can also influence sympathetic outflow at certain points and parasympathetic outflow at others (11). Spinal reflex loops, in addition to the modification of sympathetic/parasympathetic balance more globally, have been shown to contribute to some of the organ effects seen with acupuncture, such as regulation of cardiac activity (37).

Due to the invasiveness of such studies, determining the central effects of acupuncture has traditionally been limited to the use of laboratory animals. Decades of data show influences on neurotransmitters as previously discussed regarding the spinal cord, especially with regard to endogenous opioids (38). This has not answered the lingering questions about why acupuncture appears so effective for mood and behavior. However, neuroimaging studies have come of age and provided vast amounts of data, although there remains controversy as to how to value and interpret this data. Imaging studies have shown complex activation and deactivation of many areas of the brain. In general, verum acupuncture needling has shown a larger effect than sham needling, and using a deep needling treatment with adequate tissue grab (deqi) appears important (39). The periaqueductal grey area and ventrolateral medulla show consistent responses to acupuncture for pain. Signal transduction effects of acupuncture have been shown to modify CNS damage, improve healing and plasticity, increase synaptic transmission, and reduce secondary inflammatory cascades (40). 26

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Fluid Movement and Axon-Reflex Modification of Microvascular Environment Distal points are highly innervated because sympathetic and sensory fibers join peripheral arteries and travel in the interstitium as nervi vasorum until they exit at their destination and course through connective tissue. As arteries travel distally in a limb, sympathetic and sensory input becomes denser and more attenuated so that distal points tend to convey a stronger autonomic response. Distal interstitium is also less dense and organized than more proximal fascial sheets. The lymphatic streams in distal interstitium are diffuse, and the lymphatic channels are less organized. Within this interstitial area the arteriovenous anastomoses create a constant fluid movement from vascular structures to interstitial and lymphatic fluid streams (41). Thus, distal points are particularly important for microvascular fluid flux and the origin of the lymphatics, serving an important role in immune modulation (42).

Specific Activities

Acupuncture points exhibit individual specificity for a variety of reasons. The first is the location and distribution of neuromodulatory effects exerted by the point. It is recognized that the increased population of nerves and vessels around verum acupuncture points contributes to their potency when compared to sham points (8). More complex innervation near a point also contributes to increased activity across the spectrum of nervous system input, allowing sympathetic, parasympathetic, sensory (low-threshold), and pain (high-threshold) inputs. Each of these inputs relates to different spinal and central regions of recognition (43). It is rational that distal points, which contain all fiber types in a small area, can provide increased recognition due to the concentration of response to an exceedingly small area of input. This gives distal points an increased magnitude of response to the CNS compared to more proximal or axillary points and justifies the impression of ting points as “awakening” (44). Lymphatic flow is intrinsically affected by all peripheral acupuncture points, as this is the location of microvascular and lymphatic homeostasis (42). As the lymphatics become more organized, forming into ducts with valves and eventually providing home to lymph nodes, acupuncture points start to have more individualized effects (45). At about the level of the He Sea points (elbow and stifle), the first major lymphatic structures are found. Thus, points at this level (ST36, LI10) are likely to have a far more pronounced immunological effect than would more distal points or more proximal points, except those specifically found along lymphatic channels (46). Likewise, major effects altering edema formation in the distal limb will amplify

near these joints and tend to lessen both distally and proximally (again, except with points that are along the veins and lymphatic routes, such as the SP channel).

There are many verum acupuncture points that directly correlate with known myofascial trigger points and others that correlate with the tendinous attachments of muscle groups. These points are ideal for trigger point, muscle spindle, and golgi tendon treatments. Myofascial trigger point targets provide motor function and reflex activities, which regulate the neuromuscular system (example: GB34). The most established use of non-verum acupuncture points is also focused on these structures and constitutes the practice of dry needling in physical therapy practice (16, 30).

Paraspinal needling brings up local and regional neuromodulation aspects that vary quite a bit with needle placement. Organ effects of acupuncture are generally associated with the spinal nerve modulation that can occur at the inner Bladder line, as the ventral branch of the dorsal nerve root exits the fascial plane between the longissimus and iliocostalis muscle groups (36). Thus, most direct organ effects occur along this tissue plane. Additionally, the Bladder line modifies spinal nerve input from 2 to 3 spinal segments cranial to the point because the spinal nerves exit the spinal canal caudal to their place of emergence from the cord. However, the Hwato Jiaji (HJ) points are dorsal to the emerging nerve and are innervated from the same spinal segment in the dorsal branch of the spinal nerve that does not travel caudally before emerging. There-

fore, a point at L2-3 on the Bladder line (BL23) is treating the exiting spinal nerve from about T13, while a HJ point at the same level is treating the L2 spinal nerve (47) (Figure).

Example of Neurophysiological Underpinnings of an Acupuncture Treatment

Studies of acupuncture in spinal cord disease offer an enhanced understanding of its potential physiological effects. A generic acupuncture approach to the treatment of an acute, grade 3, thoracolumbar (T13-L1) spinal cord injury in a quadruped can explore these neurophysiologic concepts (Table 1). Using typical grading and classic signs, Table 1. Spinal Cord Injury Grades Favorable Prognosis Presentation Grade **All exhibit paraspinal pain (walking, control of pain) 1

Normal gait, just painful

70-100%

Weakly ambulatory or ataxic

55-100%

Non-ambulatory, unable to stand unassisted Paraplegic, no voluntary movement Deep pain present, +/- urinary & fecal continence Paraplegic, no voluntary movement Deep pain absent, +/- urinary & fecal continence

55-95%

40-80%

30-60%

Figure. Paraspinal Bladder Line Organ Relationships AHVMA Journal • Volume 63 Summer 2021

assume the patient has pelvic limb paresis with hypertonicity (upper motor neuron lesion), spinal pain, maintenance of deep pain sensation in digits, and absent conscious proprioception. Medications and surgery may be chosen to treat these cases, but acupuncture may be used as an alternative or adjunct treatment. From an acupuncture perspective, this lesion would generally be treated with at least 10 to 20 acupuncture points, with a focus on selecting points that have the greatest number of overlapping benefits. Points chosen from a list of priorities using either Traditional Chinese Veterinary Medicine (TCVM) or Western medical acupuncture (WMA) would likely be the same (Box). The number and type of points used in clinical practice might vary from the proposed points based upon patient presentation (acuity, symptoms, associated conditions, and temperament). For the purposes of this discussion, we will explore a detailed evaluation of 12 points that would commonly be chosen for unilateral or bilateral treatment (Tables 2 and 3).

All these points will share some general physiological effects common to all acupuncture points, and each of the

Box. Western Medical Acupuncture Approach to Point Selection for Painful Patient (Spinal Cord Injury) • Identify origin of pain and dysfunction to establish the needle placement locations: ° Fascia and strain patterns ° Motor and myofascial trigger points ° Intervertebral disk symptoms ° Facet joint symptoms • Acupuncture point choices- at least one point per category. Use points covering multiple categories where possible ° Homeostatic points: sedation, sympathetic and parasympathetic modulation, global analgesia ° Proximal (cranial) points (cranial to pain or lesion) ° Proximate points (for discrete local spinal pain. Use HJ groups to maximize same-segment innervation and local muscle groups) May not be tolerated in acute injury ° Distal (caudal) points (along the spine, caudal to lesion) ° Peripheral points along ventral branch or peripheral nerve emerging from the spinal segments of interest ° Myofascial trigger points and Ah Shi (painful) points

Table 2. Acupuncture Point Choices With TCVM and WMA Rationale Point Neurophysiological rationale (WMA)

GV14

Homeostatic, proximal, sympathetic chain, motor regions

Bai Hui BL11 BL18 BL23 BL36 BL40 BL54 KI1 LV3 LI4 ST36 LI10 HJ T13-L1

Homeostatic, distal along spine, sacral transition, macro-fascia, Ah Shi point Paraspinal neuromodulation, proximal along spine, myofascial strain pattern (cervical), compensatory motor groups, Ah Shi point Paraspinal neuromodulation, proximal along spine, myofascial strain pattern (longissimus) Paraspinal neuromodulation, distal along spine, myofascial strain pattern (longissimus) Proximal appendicular motor point, flexor surface (use estim), proximal sciatic point Peripheral point, flexor surface (estim), lymphatic channel, neuroimmune modulation Motor point, reflex loops, gluteal muscle and cranial gluteal nerve (widens lumbar segment input) Peripheral point, flexor surface (estim), immune, lymphatic and fluid flux, sympathetic modulation Homeostatic peripheral point, autonomic nervous system, nervi vasorum hindlimb Homeostatic peripheral point, autonomic nervous system, nervi vasorum forelimb, brachiocephalicus and spinal nuclei Homeostatic peripheral point, periarticular reflex loops, autonomic nervous system Homeostatic, peripheral, periarticular reflex loops, autonomic nervous system Homo-segmental neuromodulation, motor points for myofascial strain pattern in longissimus

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TCVM rationale

Meeting point for 6 Yang channels of hand and foot, Sea of Yang, clears pathogens, expels Wind, tonifies Qi and Yang Activates Qi and alleviates pain. Use with deficiency or excess patterns Meeting point: BL, SI, TH, GB. Influential point for bone, Sea of Blood. Benefits bones and joints, expels pathogens, treats pain Spreads Liver Qi, pacifies Wind, cools Fire and clears Damp-Heat. Treats rigidity of neck and spine, and spinal pain Spreads Kidney Qi, fortifies Yang, nourishes Yin, benefits Essence, treats lumbar pain and hemiplegia Activates BL channel, relaxes sinews and alleviates pain, regulates lower jiao He Sea and earth point, activates channel. Treats pain in lumbar spine and rear limbs from any etiology Master point for pelvic limbs. Treats pain in lumbar region, sacrum and buttocks Jing-Well point, descends excess, calms, rescues Yang. Treats lower limb paralysis, lumbar pain and stiffness Yuan-Source point, ensures Qi and blood flow, treats pain, including lumbar pain, paresis. Combined with LI4 is Four Gates Yuan-Source point, regulates defensive Qi, expels Wind, alleviates pain, restores Yang. Four Gates with LV3 He Sea and earth point, supports Qi, alleviates pain, revives Yang. Treats lumbar pain, hemiplegia, atrophy Regulates Qi and blood, alleviates pain, activates channel, Yang Ming point, invigorates forelimb Treated in TCVM as Ah Shi points

Table 3. Neurophysiological Aspects of Discussed Points Point

Micro-fascia Macro-fascia

Fluid flux

Immune

MTrP

+ +++ +++ ++ + +++ ++ + +++ + +++ + +++ + ++ + +++ + ++ + ++ ++ + ++ +++ ++ +++ +++ + + +++ +++ + + + ++ +++ ++ + +++ ++ + ++ +++ +++ ++ ++ +++ ++ +++ ++ ++ + +++ + +++ Abbreviations: MTrP, Myofascial trigger point; Symp/Para, sympathetic and parasympathetic.

GV14 Bai Hui BL11 BL18 BL23 BL36 BL40 BL54 KI1 LV3 LI4 ST36 LI10 HJ T13-L1

distinct points will also contribute unique physiological effects that separate the points. The shared effects include interaction with fascia, mechanotransduction in fibroblasts and other cell types, neuromodulation, analgesia, modulation of fluid motion, and modification of the microvascular environment. Effects that are more specific to each particular point include location and distribution of neuromodulatory effects, degree of immune modulation, muscle or trigger point effects, brain or homeostatic changes, sympathetic and parasympathetic stimulation, remote visceral organ effects, and degree of lymphatic flow modulation (Table 3).

The acupoint GV14 is regarded in TCVM as a point to treat various pain conditions due to the convergence of the 6 Yang channels from the hand and foot. In this aspect it is part of the Sea of Qi, which clears pathogenic factors, clears heat, and tonifies Qi and Yang. In this capacity it is central to treatment of obstructive pain (46). From a physiological perspective, GV14 has both micro-fascial and macro-fascial effects, with the macro-fascial effects being most relevant to the observed characteristics. There is no significant fluid or lymphatic presence to this location, and axillary points, with certain exceptions such as LU1, are generally less important than distal points for micro-fascial and microvascular input. The macro-fascial location relates to the fascial sheets that penetrate the thorax. This location is the origin of the sympathetic chain, the distribution of cervical nerve roots from the sympathetic and parasympathetic nervous system, and a region of tremendous cross talk and autonomic nervous system traffic (47). Neuromodulation is the superpower of this point, with autonomic effects that create systemic, homeostatic, and CNS modulation. Immunomodulatory and antipyretic effects at this location are attributed to vagosympathetic neuroimmune effects rather than specific effects on lymphatic

Visceral + + ++ +++ +++ +++ ++ +++ ++ -

Symp/Para homeostasis

+++ +++ + + +++ +++ +++ +++ +++ -

Central

Reflex loops

Analgesia

+++ +++ ++ ++ + +++ +++ + ++ -

+ ++ ++ ++ + + + ++ ++ +

+++ +++ +++ ++ ++ ++ +++ + + +++ +++ ++ + +

tissue. Viscera-related neural cross talk in this region is associated with pulmonary and cardiac regulation, but BL points in the region are better positioned to interact with the spinal nerves as they become superficial. GV14 also has significant motor input for a centrally located point; it approximates the insertion of the cervical muscle groups, trapezius and rhomboid groups, and the origins of the thoracic axillary groups such as the latissimus, longissimus, and iliocostalis groups. This amplifies the pain-related effects of the point, especially for back and spinal conditions, as the bridge between cervical and thoracolumbar regions. Some of these motor and autonomic effects overlap with the closest BL point, BL11, which will be discussed shortly.

Bai Hui is described as 100 Convergences in TCVM, despite being located at the lumbosacral junction in quadrupeds, rather than at the top of the head as in the human (46, 47). This sacral nature lends its indications for use to urination, as well as to pain in the lumbar region. There is less diffuse information about this point in quadrupeds due to its variation from the human and the consequent alteration of historical perspectives.

From a physiological perspective, Bai Hui has several things in common with GV14, in that it resides at the termination of input from the sympathetic chain and at the transition to sacral innervation, which thus hosts significant autonomic and somatic traffic. It also has limited micro-fascial importance and has less motor input than GV14 might. In addition to the spinal relationships, the macro-fascial plane it occupies is the conclusion of the longissimus group and the attachment of the hips and sacrum. Thus, fascia plays a more important role than muscle in this location as AHVMA Journal • Volume 63 Summer 2021

compared to GV14, where both served prominent roles. Visceral input is characterized by its proximity to sacral BL points, which have dramatic roles in pelvic visceral functions such as urination, defecation, and sexual functions.

BL11, BL18, and BL23 can be considered together because of their WMA similarities. Located within the fascial sheet containing the ventral root of the dorsal branch of the spinal nerve, they modify neuronal signals related to their specific spinal nerves and thus overlap with associated visceral structures (47). BL11 is at the beginning of the thoracic spine and treats the caudal cervical nerve roots that have some overlap with cardiac and lung innervation. For BL18, the location is at the T10/T11 spinal segments, but the nerve root is from T8/T9, which overlaps with innervation to the pleura, liver, and diaphragm. The celiac plexus forms just caudal to this region and receives input from these spinal roots. BL23 emerges between spinal segments L2/L3 but contains nerve roots from T13 to L1. In all cases, these points can treat regional spinal pain as well as distant visceral conditions. In addition to neuromodulation, which is the major focus of these points, motor effects can be seen. All 3 points emerge in the fascial plane between the longissimus and iliocostalis muscle groups. Angling the needle may also potentially provide trigger point treatment in the longissimus. In addition, BL11 occurs as the cervical groups coalesce onto the thoracic segment, making this a major location for both motor and fascia input as well as reflex loops from the forelimbs and neck region. BL18 influences the large latissimus dorsi group and thus the phrenicoabdominal nerve. BL23 interacts with the iliopsoas muscle as it attaches to the ventral aspect of the lumbar vertebral bodies. In this example these points can play roles in organ neuromodulation and perfusion (heart, lungs, liver, and kidney) in addition to pain modulation at the level of the spinal nerves. The points have limited effects on local fluid dynamics but do relate to fluid mechanics at the organ level. Immune modulation from these points is limited, as they are neither peripheral points nor located over lymphatic chains, but they do have some limited immune modulation through vagosympathetic neuroimmune balance. They all have minor effects on brain neurochemistry via their input to the spinal cord.

BL36 is a proximal appendicular point. In general, points in this category hold macro-fascial implications, connecting limbs to the body in major fascial sheets and dense collagenous attachments. BL36 also occurs close to the sciatic nerve and thus serves the role of a proximal point along this peripheral nerve, collaborating with KI1 and 30

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LV3 distally along the axon (47). BL36 is located on the flexor surface of the hindlimb. Its use, along with electrical muscle stimulation (estim), would help to restore reflex arc function along the coordinated muscle groups, promoting multi-motor group flexion to offset the extensor spasticity seen with upper motor neuron injury to the spinal cord. In TCVM, BL36 is important for its ability to activate the BL channel, regulate the lower jiao, relax sinews, and alleviate pain. It is especially used for sciatic nerve pain radiating down the limb (46).

BL40 holds importance as a He Sea and earth point in TCVM (46). It benefits the lumbar region and stifles, activates the channel, and treats pain in the lumbar spine and hindlimbs. In WMA terms, its value is due to its location in the stifle region, on the lymphatic and flexor surface of the pelvic limb (47). In addition to the reflex loop input shared with BL36 and KI1, it will have significant neuroimmune and pain modulating effects. It is the most lymphatic-centric option of the points discussed here, which is a unique and necessary benefit with pelvic limb paralysis as lymphatic flow generally requires motor activity for optimal efficiency. Mid-limb points have an increased tendency to form reflex loops with organ systems, and the urinary bladder input from the pelvic nerves is important in a spinal cord-injured patient (48). BL54 is a major motor point of the hindlimbs, interacting with the gluteal groups and piriformis and providing input near the joint capsule of the hip (47). Motor function is by far the most important aspect of this point, and through motor reflex loops it can modify motor reflexes. Via nerve pathways it also provides regional and systemic analgesia. In TCVM it is considered a master point for back and pelvic limbs, and it is used to treat pain in the lumbar region, sacrum, and buttocks (46). KI1 is a distal point which conveys a significant neurostimulatory and microvascular effect. In this presentation it provides sympathetic input and fluid and immune modulation (47). It is also the distal point along the fibular nerve, making it critical for neuronal recruitment and healing after spinal cord injury. It is on the flexor surface of the limb and could provide a good location for estim along the flexor groups when combined with BL40 or BL36. With a T13 lesion, there will be increased extensor tone to the hindlimbs, making the flexor groups important targets for stimulation and awakening. In TCVM, K1 is relevant because it is a Jing-Well point that combats descending excess, calms the spirit, revives consciousness, and rescues Yang (46). It treats lower limb paralysis, lumbar pain and stiffness, foot numbness and pain, or inability to stand.

Points LI4 and LV3 are integrally related and are very stimulating points neurophysiologically. In WMA there is a goal to stimulate several critical regions along the entire spinal cord; treating bilaterally and both forelimbs and hindlimbs can help to accomplish this wide distribution of neural input. In addition, both points are found in the distal limb, but not quite as distally as the digits which have less soft tissue and fewer nerve structures for modulation in quadrupeds as compared to humans. At the level of metatarsal (or metacarpal) and phalangeal joints, the innervation and blood flow from the limb form complex loops that can bypass the distal digits and return blood flow to the venous system (47). The degree of innervation at this region is marked and includes significant sympathetic, parasympathetic, and sensory fibers. Thus, these are the most distal points in dogs and cats that carry vast autonomic and somatic information to the nervous system, providing both peripheral effects as well as intense neuroregulatory and immune-modifying benefits. Since this neurological activity also translates into a larger central action, both points can be considered to have homeostatic effects. Likewise, in TCVM both points are thought to have generalized analgesic effects (46). They are Yuan-Source points, which is relevant to the lymphatic flow coalescing in this region. Used together, they are known as the Four Gates, and they restore blood flow and Qi and treat pain and weakness. In addition, LI4 has innervation overlap in the cervical region with spinal nuclei of the trigeminal and axillary nerves (47). This explains the TCVM recognition of this point for treating conditions of the face and serves the WMA imperative of creating a far-reaching neuromodulatory input to the nervous system (46). Points ST36 and LI10 can also be considered together. Acupuncture needle distribution is anecdotally believed to benefit from bilateral as well as multiple-limb treatments to stimulate multiple regions along the spinal cord, rather than just a few or just the affected spinal segments. On both the thoracic and pelvic limb, these points occur just distal to the first identified lymph node chains and in the region of the He Sea points. This correlates with the anatomy, as the lymphatic channels are well formed at this level and do function as the “rivers” proposed by TCVM theory. In addition, these 2 locations benefit from significant autonomic reflex loops, with ST36 involved in gastrointestinal regulation and LI10 and other elbow points playing an important role in cardiac reflex loops (49, 50). In TCVM theory, the use or combination of these points is strengthening, with ST36 said to support Qi, alleviate pain, revive Yang, and treat lumbar pain, hemiplegia, and hindlimb atrophy (46). LI10 is said to regulate Qi and blood, alleviate pain, activate the LI channel, and invigorate the

forelimb, which can be important especially in cases with absent motor activity in the hindlimbs.

All HJ points are primarily motor and analgesic points. They stand out for being homo-segmental and are often the best points to treat an acutely painful region of the spinal cord. They interact with the spinal stabilizer muscle groups as well as the longissimus. In TCVM, these points are selected to address focal discomfort and do not have any notable alternative associations. In this case they relate to the origin of the spinal pain.

Evaluating this set of acupuncture points is somewhat artificial since patient-based point prescriptions, which cannot be anticipated in this generic process, are intrinsic to a successful acupuncture treatment. However, the concepts behind these points demonstrate the diversity of functions that can be attained and the desirability of a broad approach for the treatment of multi-systemic diseases such as spinal cord injury. A variety of other points could be chosen, using both TCVM and WMA-based thinking to capture the underlying effects discussed for this specific cluster of acupuncture points. In conclusion, while a scientific discussion of acupuncture may benefit scholarship via evidence-based conversation, when considering a specific case presentation, TCVM and WMA are likely to select similar points, albeit via disparate thought processes. These points come together to address various physiological mechanisms and underlie the complexity and diversity of treatment at an acupuncture point. Depth of needling, type of needles, and associated treatments such as manual therapy, pharmaceuticals, non-pharmaceutical herbal medications, and exercise further complicate evidence-based research on acupuncture but are commonly utilized in clinical medicine. Creating a collaborative conversation between neurophysiological acupuncturists and TCVM acupuncturists is not only possible, but it is also good for the field of acupuncture. Basic scientific evidence of the neurophysiology of acupuncture can serve as a scaffolding for these conversations.

Acknowledgement The author wishes to acknowledge Susan Neary, DVM for her contributions to this paper.

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Scientific Review

Vibrational Medicine: The Tuning Fork as a Therapeutic Modality Jennifer M. Hebel, DVM, PhD

Author Contact: Five Elements Veterinary Alternatives 3125 South 61st Avenue Omaha, NE 68106 402-614-6075 drjenhebel@5elementsveterinary.com

Abbreviations

Abstract

treat soft tissue injuries (1). These electronic devices present several barriers preventing use by general practitioners, including significant capital investment, additional required training or certification, and finite working life. Ultrasound can have adverse effects such as thermal damage to tissue. Shock wave therapy may be uncomfortable or stressful for some veterinary patients. In contrast, a tuning fork is a relatively simple, inexpensive acoustic device that offers a more durable and accessible method of delivering focal sound waves to tissue. When applied directly to the body, tuning forks can be used as an adjunct to other types of bodywork, with application during massage and manual therapy treatment, and serve as a gentle, alternate method to stimulate acupuncture points. Reported benefits of tuning fork therapy are similar to other manual therapy modalities, including relaxation, reduction of pain and swelling, improved lymphatic flow, and myofascial release (2).

Sound therapy is an emerging type of energy healing that utilizes instruments played live in close proximity to the patient. Sound vibrations at specific frequencies are heard by the patient and absorbed by the patient’s body to initiate healing. A tuning fork is a simple vibrational instrument that can deliver specific frequencies near or on anatomical regions of the body. Benefits of tuning fork therapy include relaxation, reduction in pain and swelling, and myofascial trigger point release. Tuning forks can also be used to stimulate acupuncture points. Although the current scientific research on sound therapy is limited, multiple therapists over the last few decades have independently developed tuning fork therapy methods based on principles of music theory and guided by empirical evidence of positive response to treatment. This article explains how vibration and music theory are applied in sound therapy and describes the use of tuning forks as a potential new bodywork therapy for veterinary patients.

Introduction

Sound energy is currently used as both a diagnostic and healing modality in veterinary medicine. Diagnostic ultrasound is perhaps the most widely used in veterinary medicine, readily available in many general practices. Therapeutic ultrasound and extracorporeal shock wave therapy are modalities used in veterinary rehabilitation therapy to

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Hz Hertz RFR Resonant Frequency Range

Tuning forks are often included in the relatively new holistic medicine genre known as sound healing or sound therapy. Unlike music therapy which exposes the patient to composed music recordings, sound therapy uses either single frequency or multiple frequency sounds created with instruments played in the presence of the patient. Whereas music therapy focuses on positive physiological effects from an auditory experience, sound therapy includes possible effects of sound vibration directly on the

physical body (3-9). Multiple instruments, including gongs, Himalayan singing bowls, rattles, drums, didgeridoo, and the human voice, are used to generate the sound vibrations in close proximity to the patient (9-10). It is theorized that healing occurs both from the auditory and corporeal experience of the sound vibrations. Some instruments such as Himalayan singing bowls or tuning forks can be applied directly to parts of the body. Himalayan singing bowls (also sometimes referred to as Tibetan singing bowls) are metal alloy bowls that have been made in India, Nepal, and Tibet for the last 2400 years. They continue to be used as an aid in meditation and spiritual practice (10). The bowl can generate different types of sounds depending on whether it is struck like a bell or resonated with a feltcovered wooden mallet stroked around the rim of the bowl, creating a singing sound similar to that evoked by stroking the rim of a wine glass. Larger bowls can be placed near the patient, whereas smaller ones can be placed directly on the patient’s body. In contrast, a tuning fork is a metal device commonly known to deliver a pure tone when tuning a musical instrument. It is only in the last few decades that tuning forks have become a therapeutic tool applied in holistic modalities like massage and acupuncture. Tuning forks emit a single fundamental frequency providing a versatile and practical way to deliver focal sound healing to veterinary patients. This article reviews the basic science of sound vibration as a healing modality and introduces the fork as a novel tool to promote relaxation, pain relief, and soft tissue healing in animals.

Basic Principles of Vibration

Sound is a pressure wave of energy created by the vibration of an object. For the pressure wave to propagate, the vibrating object must be surrounded by an elastic medium such as air, water, wood, muscle, tendon, or bone. The rate of vibration (the number of cycles per second) is known as the frequency and is measured in Hertz (Hz) (11). Animals and humans perceive these pressure waves as audible sounds when the waves interact with the tympanic membrane in the ear. The hearing perception range is approximately 20 to 20,000 Hz for humans, 50 to 45,000 Hz for dogs, and 45 to 64,000 Hz for cats (11, 12). In addition to intensity and duration, frequency is a key component of both auditory and non-auditory vibration and contributes to the effects that vibration has on living tissue. The musical term “pitch” is helpful in describing the experience of a specific frequency. Pitch is related to frequency as a subjective way to ascertain whether a sound is perceived as “high” or “low” (11). Pitch can also describe what is an accepted sound for a specific musical note, whereas the

frequency is a numerical measurement of cycles per second for that note. Notes in the Western musical scale are indicated by the capital letters A, B, C, D, E, F, and G, though it is up to the musical community at the time to decide which pitch/frequency relates to each note. For example, the musical note “A” may be played at 440 Hz as an agreed upon pitch to be tuned by an orchestra, while another orchestra may tune to “A” at 444 Hz for a slightly different pitch. The note a half-step higher than the fundamental note is said to be “sharp” (indicated by a # sign following the note), while the note a half-step lower is “flat” (indicated by a ♭sign following the note). The range of 8 notes “C” through the next higher “C” constitutes an octave, with the higher “C” having a pitch twice the frequency of the lower “C” (Figure 1).

Figure 1

The Western musical scale overlaid on a piano keyboard. A standard piano keyboard has 7 full octaves in which the white keys are the major keys (fundamental notes) and the black keys are the minor keys (sharps and flats). The minor keys can be described by 2 different notes with the identical pitch (either a half step up or a half step down from the fundamental note). The piano is organized with the lowest frequencies on the left, increasing to the highest frequencies on the right. The octave, 8 full tones, spanning from “C” (128 Hz) to “C” (256 Hz), is indicated by brackets.

Pitch can also relate to the emotional quality that the sound invokes. Higher pitches have faster, shorter oscillations and may be uncomfortable to listen to, whereas sounds with lower pitches have longer, slower oscillations which tend to be more calming and grounding. Depending on their intensity and duration of exposure, some pitches can be painful or damaging to the ear. Sounds at frequencies higher than the human hearing range are termed ultrasound, and those lower are infrasound (11, 12). Exposure to ultrasounds usually comes from medical devices such as diagnostic or therapeutic ultrasound machines or other types of electronic equipment. However, we are naturally exposed to extremely low-frequency vibrations arising from AHVMA Journal • Volume 63 Summer 2021

Sound in both the audible and inaudible ranges applied on or near the body may also be perceived as vibration sense or pallesthesia. Many animals, especially birds and reptiles, have developed complicated organs for both generation and reception of vibration as a form of communication. Such adaptations are useful for predatorprey relationships and various aspects of reproduction (14). In mammals, vibration detection organs are primarily concentrated in the skin, although tissues such as muscle, periosteum, and hair follicles also contain mechanoreceptors (15). Of the 8 mechanoreceptors in the skin, Pacinian corpuscles and Meissner’s corpuscles are the most important for the perception of vibration. Meissner’s corpuscles are located in superficial layers of the skin and detect low-frequency vibration. In contrast, Pacinian corpuscles reside in the subcutaneous tissue and detect high-frequency vibration (15). Hair follicles, especially specialized whiskers or vibrissae, can sense vibration through associated sensory nerve endings. The neuroanatomy of the vibrissae sensory organ and its relationship to the sensory cortex has been extensively studied in rodents. Each whisker has a corresponding column or “barrel” of neurons in a somatotopic pattern on the contralateral sensory cortex. These columns of neurons are often called “whisker barrels” (15). Recently, it has been found that each whisker is tuned to respond to a very narrow bandwidth of frequencies. Shorter whiskers are more rostral and respond to higher frequencies, while longer whiskers are more caudal and respond to lower frequencies (16). How this vibrational information is processed and used to direct the animal’s behavior remains to be elucidated. From a mechanical standpoint, when vibration is applied to the body such as via a vibrating tuning fork, the sound is propagated through both the liquid and solid components of the tissue. The sound waves may either diminish (dampen) or resonate as they pass through tissues. Different organs and regions of the body have a “natural” or resonant frequency. A resonant frequency is the frequency at which an object vibrates most readily and can amplify the vibration (17). Most research into the resonant frequencies of animals and humans has focused on the potential of vibration to damage organs in occupational health or research animal facility settings (16). A resonant frequency range (RFR) is a mathematically 36

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calculated range of natural resonance frequencies for either an organ, body region, or entire organism. In response to a given force, tissues or organisms with higher mass, stiffness, or dampening will tend to vibrate less and have a lower RFR. For example, mice have a measured RFR of 41-100 Hz and rats 31-50 Hz (18-20). Exposure to frequencies in or near the RFR of the organism may have either harmful or therapeutic benefits depending on many factors, including the amplitude, duration, and focal aspects of the vibration exposure, individual differences, or presence of pathology. June Leslie Wieder, DC, has determined the unique resonant frequency of each vertebra in the human spine and used this information to treat patients with tuning forks in her chiropractic practice (23). In the future, a better understanding of the RFR of different tissues in veterinary patients may aid in the selection of frequencies for therapeutic benefit. Until then, the choice of therapeutic frequencies is guided by empirical evidence from practitioners based on the mathematics of music theory.

Tuning Fork Physics and Music Theory

In a clinical setting, a tuning fork is simple way to deliver a specific frequency to the body. A tuning fork is a metal acoustic resonator that, when struck, generates a reproducible sound frequency. The tuning fork has 2 equally long tines attached to a stem. Tuning forks are precisely cut from a single piece of aluminum or steel. Modern tuning forks are most commonly made of aluminum since these

Figure 2

Weighted (left) and unweighted (right) forks used in tuning fork therapy. Weighted forks are applied to the body whereas unweighted forks are moved through the space near the head and body of the patient.

Photo by Tracey Fichtl

the earth such as ocean waves, tornadoes, earthquakes, and avalanches. The Schumann Resonance is a well-known resonance between the earth and the ionosphere which pulses at an average of 8 Hz, well below the auditory range of most mammals (13).

tend to resonate longer. Tuning forks may be unweighted or weighted (Figure 2). For therapeutic use, weights have been added to the tines to make them vibrate longer when in physical contact with the body, up to approximately 30 seconds (2). Of all sound healing instruments, tuning forks are the easiest to learn to “play” and are lightweight, portable, and inexpensive, all of which make them attractive equipment for use in working with animals. Unlike other instruments, the tuning fork is very durable and will never go out of tune unless physically damaged.

A tuning fork is activated by striking either of the tines on a solid object. Due to the property of acoustic resonance, once a tine starts vibrating, the other tine will start vibrating at the same frequency. When the tuning fork tines start to vibrate, the air particles nearby move rapidly and create pressure waves. As the tines move toward each other they compress the air molecules, and as they move away from each other they create a lower pressure area (known as a rarefaction) that sucks the air molecules apart. The rhythmic motion of the tines produces a pressure wave with a specific frequency (11). The length of the tines determines the pitch of a tuning fork; longer tines produce lower frequency vibrations and vice versa. Most therapeutic tuning fork frequencies range from approximately 60 to 1200 Hz, as these frequencies seem to be comfortable for the patient and the therapist (2, 6). A fundamental understanding of music theory becomes relevant to sound therapy because both single frequencies and pairs of frequencies (known as intervals) are used as a basis for the therapeutic application of tuning forks. When struck, the “C” fork will vibrate the loudest at 256 Hz, but will also simultaneously produce other notes, called overtones, at mathematically predictable frequencies. This organizational structure of frequencies is known as a harmonic series (Figure 3a). Pairs of notes in the harmonic series, called intervals, are easily visualized as combinations of keys on the piano (Figure 3b). Intervals are commonly used in tuning fork therapy because of their particular vibrational qualities. For example, the Perfect Fifth interval is pleasant and soothing while the Major Third is more dissonant. However, both may be useful for different applications. The generation of overtones is thought to enhance healing when using live instruments or voice as the modality as opposed to computer-generated tones (2, 6-9).

Historical Use of Tuning Forks

While there is some evidence that the early Egyptians used a form of stone tuning fork, the British musician John Shore is most often credited with developing the first tuning fork in 1711 to provide a standard tone with which to tune a

Figure 3a

A chart of the first part of the harmonic series for the fundamental note “C” (128Hz). By knowing the ratio or the multiple, one can predict the frequency for each additional harmonic note. In this example, to determine the Perfect 5th of “C,” one can either multiply the “C” (256 Hz) by 1.5 or calculate a 3:2 ratio from the higher frequency to lower frequency. Either way, the same answer is achieved: “G” (384 Hz).

Figure 3b

The harmonic intervals of the Perfect Fifth and the Major Third visualized on a piano keyboard. Another method of calculating a Perfect Fifth for a fundamental note “C” (256Hz) is finding the note 7 half steps (white and black keys) higher than “C,” which is a “G” as indicated in brackets. The Major Third is 4 half steps higher than “C” which is an “E.” musical instrument (2). By the end of the 19 th century, with improvements in the manufacturing process, tuning forks had become a precision scientific instrument used in experiments in acoustic physics. While electronic sound measurement devices largely replaced them in the 20 th century, tuning forks continue to be used to teach students basic acoustic principles in science labs today.

Medical practitioners in the 19th century found applications for tuning forks. Tuning forks have long been used in rural or field medicine for diagnosing fractures (24). The frequency of 128 Hz readily resonates in bone (6). To test for a fracture, a 128 Hz tuning fork was applied to the end of a long bone while the practitioner listened with a stethoscope at the opposite end. If there was a fracture, the sound vibration was diminished or absent. When applied to the AHVMA Journal • Volume 63 Summer 2021

feet, the 128 Hz tuning fork could help diagnose diabetic neuropathy in humans (25, 26). In this test, the vibrating tuning fork was applied to a patient’s foot, and the length of time that the patient could detect the vibration was measured. The test was repeated at both the hallux and the 5th metatarsal head to assess different nerve pathways. Patients with neuropathy could detect the vibration for a significantly shorter period of time than patients without neuropathy. In audiology, 256 and 1024 Hz tuning forks were used to diagnose upper and lower frequency hearing loss (27). Many of these simple applications are still used today.

Sound Healing Research

There are very few published reports of clinical research using sound healing modalities. Conventional scientific methodology is challenging to apply to subtle healing modalities, which may explain the lack of publications, or there may be little interest at this time. In a small study of 51 human participants, Himalayan singing bowls were used prior to a guided relaxation in the experimental group, compared with silence before guided relaxation in the control group. They found a significant decrease in heart rate and blood pressure in the group that received the singing bowl treatment (28). A considerable number of participants in a Himalayan singing bowl meditation reported decreased tension, anger, frustration, and signs of depression with increased spiritual well-being after the sound meditation (29). Entrainment may help explain the effects seen in these studies. Entrainment occurs when the natural oscillatory patterns, frequency, or rhythm of an object is changed by another object. The system with the slower frequency speeds up, and the faster system slows down until they synchronize. For example, Circadian rhythms can be shifted to different day/night light cycles as the endogenous biological rhythm becomes entrained to environmental cues (30). Heart or respiratory rates will synchronize among groups of people involved in emotionally charged or empathic situations; therefore heart rate entrainment may explain the parasympathetic and psychosocial changes found in these studies (31, 32). Another possibility is brainwave entrainment. Brain waves are easily entrained using binaural beats, sounds delivered to each ear with slightly different frequencies, synchronizing cortical brain waves to different brain wave states (such as alpha, delta, or beta wave) to achieve a therapeutic effect (33). Thus, sound or vibration could be used to intentionally “tune” biological systems.

While there have been few studies on the effects of vibrational therapy at the tissue, cellular, or molecular level, a large body of research has focused on human occu38

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pational and laboratory animal exposure to environmental sound and vibration. Non-auditory sound and vibration have been shown to influence nearly every organ system in the body, including the endocrine, cardiovascular, neurological, immune, reproductive, and gastrointestinal systems. This literature has been thoroughly reviewed by Reynolds (12). The majority of these effects are negative in nature, such as increased stress hormone production, increased blood pressure and heart rate, decreased reproductive rate, or disruption of myelinated nerves. However, other studies have shown beneficial effects on bone healing, wound healing, and muscle tissue. Mechanical vibration has been shown to increase bone healing through the proliferation of mesenchymal stem cells and osteoblast formation in vitro and accelerate fracture healing in rats and sheep (34-36). Application of whole body, low-intensity vibration at 30-90 Hz improved wound healing in diabetic mice (37). Human exposure to a whole body vibration device at 5 Hz significantly increased muscle relaxation in individuals with neck and back pain (38). In addition, vibration therapy at 60 Hz reversed the loss of neuromuscular junctions in ovariectomized rats (39). In the future, research protocols will need to be refined and standardized to separate potential beneficial versus harmful effects of vibration on biological systems. It is plausible to speculate that the cellular mechanisms induced by vibration are at least in part mediated by global mechanical changes in the fascia. While fascia is often the “forgotten tissue” in medical training, it a complex organ consisting of a crystalline collagen web that envelopes and supports all body structures. It contains collagen, extracellular matrix, fibroblasts, immune cells, and other specialized cells including telocytes (40). Since fascia has also been shown to have semiconductive, piezoelectric, and photoconductive properties and is intimately associated with the autonomic nervous system, it is perfectly poised to mediate many of the effects of energy healing modalities (41-44). However, despite much investigation into fascial properties, it is functionally difficult to measure whether fascia is “healed” (45). A recent advance in the application of musculoskeletal ultrasound may provide a possible method to visualize the release of a trigger point with applied vibration (46). Taken together, despite the scarcity of direct scientific evidence for sound healing, the large body of empirical evidence in favor of its benefits is compelling. This success is supported by the increased number of books and hands-on training courses in tuning fork therapy over the last 10 years, with a comprehensive book dedicated to sound healing with tuning forks for animals (47).

Application of Tuning Forks in Holistic Veterinary Medicine Over the last few decades, several independent holistic practitioners have explored the use of tuning forks for relieving stress, anxiety, and musculoskeletal pain (2, 6-10, 23, 47, 48). These early pioneers in tuning fork therapy for humans developed their proprietary methods from empirically derived data through their work with clients. These methods can be grouped into 2 main categories: biofield techniques and bodywork techniques. The biofield is a collective term for the clinically relevant electrical, magnetic, and biophotonic fields generated by living organisms (49, 50). A working definition of the biofield is found in a review by Hammerschlag, stating that “biologically-generated fields (biofields) are a spatially distributed set of forces and physical properties that have the capacity to encode information and exert instructive influences on cells and tissues capable of perceiving and being modified by them” (49). Not only do organisms create biofields around them, but their biofield may be influenced by the proximity of another organism’s biofield or other electromagnetic fields in their environment, which can affect both behavior and physiology. Veterinarians will be most familiar with electrical biofields measured by electrodes placed on the body during an electrocardiogram. However, the heart’s electromagnetic field can be detected up several feet away using a specialized magnetometer (51). Within a similar distance, animals and people can detect information regarding emotional states through changes in heart rate variability, and heart rates can become synchronized (32). In addition to electromagnetic fields understood by Newtonian physics, new research is emerging that reveals that quantum fields are also generated by living things, although their clinical significance is not well understood (52). In the future, a model that unifies both conventional, Newtonian, and quantum physics will likely be able to describe many of the energy healing modalities that have previously lacked scientific explanation. In sound therapy, higher frequency, unweighted tuning forks can be applied to the biofield. Vibration from an unweighted tuning fork passing over a patient may be used to alter the biofield and influence their emotional and physiological state. An example of using unweighted forks is the Biofield Tuning method developed by Eileen McCusick (8). A trained practitioner can identify abnormalities in an area as a tuning fork is passed about 15-25 cm (6-10 in) above the body. The exact frequency of the tuning fork is not important when using this technique, however, it should be a frequency with which the therapist is comfortable.

The trained therapist can hear differences or feel a dissonant vibration in the fork over areas that contain abnormalities. Such abnormalities may be from known diseased organs, areas of pain, past fractures, or surgery sites, or the patient may be unaware of any problem in that region. The area is “cleared” by repeated passes with the tuning fork and often aided by an intuitively guided discussion with the patient of possible past traumas to the region (8). Thus, the tuning fork is both a diagnostic and a therapeutic tool.

John Beaulieu describes a similar technique with unweighted forks and offers many different treatment paradigms based on a series of tuning forks with frequencies taken from the mathematics of music theory, sacred geometry, and planetary harmonics (6). Additional methods use a series of tuning forks spiraled over the Chakra system of the body. Each Chakra is said to have its own frequency; however, since there is no way to quantify this consistently, it is a subject of much debate (6-10, 48). Although the application of tuning forks to the biofield may sound esoteric, there is a growing body of evidence that other biofield therapies such as Reiki offer significant benefits in musculoskeletal pain reduction, with moderate success in treating cancer pain, dementia, and anxiety (53). Since the biofield methods require either a strong intuitive capacity of the therapist or the patient to actively participate in the healing treatment, they are more difficult to apply to veterinary patients.

The second category of therapy using weighted tuning forks for bodywork can be more easily integrated into veterinary practice as an adjunct to massage, chiropractic, or manual therapy modalities. A simple method involves applying a single frequency of weighted tuning fork to acupuncture points or areas with known tissue pain or trauma (2) (Figure 4). In this method, the bottom of the stem of a weighted tuning fork may be applied directly to the bones and fibrous structures around a joint, palpated trigger points, or tight muscles or tendons, usually with a small amount of pressure. Areas of muscle damage, swelling, or past trauma may produce a dissonant vibration in the tuning fork or may rapidly dampen the tuning fork’s vibration. Sound will travel throughout the local body region, so it is not imperative to use it at precise anatomical locations. The author has found the stem may also be applied in a “painting” motion across larger areas of swollen or painful soft tissue structures, areas of scar tissue, or applied to a tendon with gentle traction. The therapist will repeatedly apply the same or different frequencies of tuning forks to the affected area until the vibration returns to normal or improvement is palpable. Some therapists suggest that 2 to 3 applications per location are AHVMA Journal • Volume 63 Summer 2021

Figure 4

Photo by Tracey Fichtl

A weighted Ohm 136.1 Hz tuning fork is applied to the acupoint Bai Hui on a greyhound. Application of vibration at Bai Hui is considered calming and grounding, therefore an appropriate point to use to begin a tuning fork therapy session. The tuning fork is held in place by placing the index finger in the notch and fanning the fingers to support and balance the fork while maintaining consistent contact with the patient. sufficient, while stubborn trigger points may require repeated treatments (2, 6).

Contraindications for tuning fork therapy include placing weighted tuning forks in direct contact with areas where intense vibration may cause increased blood flow to tumors or mechanically disrupt early phases of wound closure. Caution should be used during pregnancy since stimulation of certain acupoints is contraindicated. Sound vibration should not be directly applied to the uterus (2, 47, 48).

While the simple application of tuning forks can be learned from the literature referenced in this article, it is prudent to receive additional training. Many courses intended for human therapists are open to veterinarians. Application of weighted tuning forks to the body in this manner involves a basic knowledge of anatomy and palpation skills, both of which can be taught to clients to provide treatment for their animals at home. 40

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Although nearly any single frequency of weighted tuning fork could be used, the frequencies of the ancient sound of Ohm (also written as Om or Aum) are commonly used for general bodywork and relaxation (2, 47, 48). Ohm is an ancient sound originally used in vocal toning during prayer and meditation in the Hindu culture. Ohm is still commonly chanted in some types of yoga and meditation. Since Ohm traditionally relates to an earth vibration, the vibration is relaxing, grounding, and gently releasing to tight tissue (2, 47, 48). Ohm frequency tuning forks are readily available in a variety of octaves. The mid-Ohm frequency vibrates at 136.1 Hz, approximately a “C#” (138.59 Hz) on the A440 scale. In the author’s experience, most animals, especially cats and small dogs, are very comfortable with the use of weighted tuning forks in the mid-Ohm frequency. A lower octave of Ohm (68.05 Hz) can be used to treat larger animals or to release very tight, dense tissue. In contrast, higher octaves of Ohm (272.2 Hz and 544.4 Hz) can be delivered with unweighted tuning forks above the body to smooth and clear the biofield at the beginning or end of a session for a calming effect. Unweighted Ohm forks can also be used to treat animals that resist being touched with weighted forks. In general, Ohm frequency forks are extremely versatile and can be used for most indications in almost any species.

AcutonicsTM is a more advanced tuning fork method that utilizes a background knowledge of the acupuncture points and meridians of Traditional Chinese Medicine. Acupuncture meridians are pathways in the body that carry vital information in the body, known traditionally as the concept of Qi. The meridians appear to align with major fascial patterns laid down in embryological development (54). Acupuncture points are surface points on the body that can be stimulated by mechanical methods such as digital pressure (acupressure), needle insertion (acupuncture), or injection of a liquid (aquapuncture) to influence the flow of Qi along the meridians. The ultimate treatment goal is to eliminate blockages of Qi that may be causing pain, organ dysfunction, or disease and restore the free flow of Qi throughout the body for optimum wellness. While originally developed to provide acupuncture treatment to human trauma patients who would not accept needles, the AcutonicsTM method was eventually adapted for animals (47, 48).

AcutonicsTM applies Chinese Medicine treatment concepts while using vibrating tuning forks to stimulate acupuncture points as a form of sonipuncture, stimulating acupoints with sound. Sonipuncture with tuning forks is gentle, non-invasive, and readily accepted by most veterinary patients. For the veterinarian trained in Traditional

Chinese Veterinary Medicine, this can be a useful adjunct for patients that are averse to traditional needling techniques. Practically speaking, since the practitioner can only activate 2 tuning forks at a time (1 in each hand), the treatment protocols use either single or pairs of points simultaneously. Different strategies can be used in choosing pairs of acupoints depending on the indication. Any acupuncture treatment plan may be adapted for use with tuning forks (47, 48). These may be pairs of local points, as in those surrounding a joint, bilateral points, or a combination of traditionally used points for more global effects. In the AcutonicsTM method, the frequencies used either individually or in pairs are derived from musical intervals and ancient celestial concepts known as the Music of the Spheres to provide different qualities. Such effects may be perceived as relaxation, activation, warming, or cooling (47, 48).

Two common intervals used in tuning fork therapy were described above, the Perfect Fifth and the Major Third (Figure 3a, b). A Perfect Fifth can be applied to the body by activating a “C” and a “G” tuning fork together (6, 7). This interval is very melodic and pleasing to the human ear, is gently opening and relaxing to tissue, and can be used in animals of any size or temperament. In the AcutonicsTM method, the Perfect Fifth is considered pain-relieving, relaxing, and opening, especially along the spine, making it useful for acute back and neck pain (47, 48). In contrast, the Major Third can be created by applying a “C” fork and an “E” fork simultaneously (6, 7). Qualitatively, this interval is cooling and calming but also dispersing and dispelling. As the vibrations are more dissonant than the Perfect Fifth, this interval is helpful for releasing tight muscles, tendons, or trigger points and for relieving pain and stagnation in the body, especially on larger dogs. It can help release adhesions and restore circulation and fascial glide (47, 48). It is also useful to break up scar tissue, especially at postoperative sites. The author has observed both tissue reorganization and hair regrowth over old scar tissue after doing a few treatments with the Major Third interval in a canine patient. Weighted tuning forks should only be placed on the scar tissue after the wound has healed (approximately 14 days), whereas unweighted tuning forks can be used in the space over a surgical site or wound immediately. Tuning forks provide a practical, economical, and effective instrument to use as a sound therapy modality in veterinary patients. Any tuning fork method described above may be adapted and applied to veterinary patients. There are many other series of tuning fork tones and treatment paradigms available that go beyond the scope of this article. Although the author’s primary experience using

tuning forks is limited to small animals, horses and exotic animals are reported to respond to these techniques. Unweighted tuning fork methods are appropriate for animals that do not want to be touched or over regions with open wounds or recent surgeries. Weighted tuning forks are suitable for bodywork intended to provide relaxation, relieve pain, decrease swelling, provide myofascial release, and in place of needles for stimulating acupoints. However, treatment applications do not need to be limited to the currently known methodologies. The creativity and intuition of the practitioner can yield new treatment applications. Sound therapy is emerging as an exciting new modality of energy healing. As this field develops, more research is needed to guide the development of clinical techniques and attempt to elucidate the underlying biophysics of how sound vibration facilitates healing. Acknowledgements The author declares that there were no conflicts of interest.

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42. Tesarz J, Hoheisel U, Wiedenhöfer B, Mense S. Sensory innervation of the thoracolumbar fascia in rats and humans. Neuroscience. 2011;194:302-308. doi:10.1016/ j.neuroscience.2011.07.066

43. Schleip R, Klingler W, Lehmann-Horn F. Active fascial contractility: fascia may be able to contract in a smooth muscle-like manner and thereby influence musculoskeletal dynamics. Med Hypotheses. 2005;65(2):273-277. doi:10.1016/j.mehy.2005.03.005

44. Fede C, Pirri C, Fan C, et al. A closer look at the cellular and molecular components of the deep/muscular fasciae. Int J Mol Sci. 2021;22(3):1411. doi:10.3390/ijms22031411

45. Lau FH, Pomahac B. Wound healing in acutely injured fascia. Wound Repair Regen. 2014;22(suppl 1):14-17. doi:10.1111/ wrr.12165

47. Ponton J, Ponton P. Acutonics small-animal therapeutics. In: Acutonics for Dogs & Cats — Sound Healing for Animal Health. Devachan Press; 2011:122-155.

48. Carey D, de Muynck M. Ohm, intervals, and archetypes. In: Acutonics: There’s no place like Ohm, Sound Healing, Oriental Medicine, and the Cosmic Mysteries. Devachan Press; 2017:72-102.

49. Hammerschlag R, Levin M, McCraty R, et al. Biofield physiology: a framework for an emerging discipline. Glob Adv Health Med. 2015;4(1_suppl)(suppl):35-41. doi:10.7453/ gahmj.2015.015.suppl 50. Rubik B, Muehsam D, Hammerschlag R, Jain S. Biofield science and healing: history, terminology, and concepts. Glob Adv Health Med. 2015;4(1_suppl)(suppl):8-14. doi:10.7453/ gahmj.2015.038.suppl

51. Kafatos MC, Chevalier G, Chopra D, Hubacher J, Kak S, Theise ND. Biofield science: current physics perspectives. Glob Adv Health Med. 2015;4(1_suppl)(suppl):25-34. doi:10.7453/ gahmj.2015.011.suppl

52. Steinhoff U, Schnabel A, Burghoff M, et al. Spatial distribution of cardiac magnetic vector fields acquired from 3120 SQUID positions. Neurol Clin Neurophysiol. 2004;2004:59.

53. Jain S, Mills PJ. Biofield therapies: helpful or full of hype? A best evidence synthesis. Int J Behav Med. 2010;17(1):1-16. doi:10.1007/s12529-009-9062-4

54. Bai Y, Wang J, Wu JP, et al. Review of evidence suggesting that the fascia network could be the anatomical basis for acupoints and meridians in the human body. Evid Based Complement Alternat Med. 2011;2011:260510. doi:10.1155/2011/260510

46. Ballyns JJ, Turo D, Otto P, et al. Office-based elastographic technique for quantifying mechanical properties of skeletal muscle. J Ultrasound Med. 2012;31(8):1209-1219. doi:10.7863/ jum.2012.31.8.1209

AHVMA Journal • Volume 63 Summer 2021

Scientific Review

The Role of Movement and Physical Rehabilitation in Connective Tissue Maintenance and Healing Jo L. Moyes, LVMT and Pedro L. Rivera, DVM

Author Contact: Jo L. Moyes, LVMT Chattanooga Holistic Animal Institute 918 E. Main St. Chattanooga, TN 37408 Phone: (423) 531-8899, ext. 2 Email: chairehab@gmail.com

Abbreviations ECM PROM ROM

Extracellular matrix Passive range of motion Range of motion

Pedro L. Rivera, DVM Healing Oasis Wellness Center 2555 Wisconsin St. Sturtevant, WI 53177-1825 Phone: (262) 898-1680 Email: contact@healingoasis.edu

Abstract

clarity, emphasis will be given to the definition adopted by the Fascia Nomenclature Committee of the Fascia Research Society: “a sheath, a sheet, or any other dissectible aggregations of connective tissue that forms beneath the skin to attach, enclose, and separate muscles and other internal organs” (3).

Connective tissues play a vital role in providing support and stability as well as the transmission of force from one area to another. The health and maintenance of these tissues is necessary for effective and comfortable movement, but they are frequently subject to injury. Evidence has shown that disuse and overuse both lead to degenerative changes, supporting the need for rehabilitation during the healing process. This paper explores the importance of appropriate stimulation in the maintenance and healing of connective tissue and the effects of immobilization and excessive loading. It also examines how postsurgical and postinjury physical rehabilitation has been shown to improve patient outcomes in clinical studies.

Fascia

Connective tissue has complex physiological characteristics. Some recent discoveries have led to different definitions of the term fascia in the literature (1, 2). For

Fascia is often divided into “superficial” and “deep” based on the location and function. Superficial fascia lies directly beneath the skin and is associated with cutaneous muscles

Introduction

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This paper examines how certain connective tissues, specifically fascia, cartilage, tendons, and ligaments, function as mechanoreceptors and how appropriate rehabilitation aids in maintaining proper conditioning and improves healing of these tissues. It also discusses the role of physical rehabilitation in enhancing patient outcomes when addressing injury, disease, and surgical intervention.

and fat deposits. Deep fascia is made up of broad, fibrous tissues that surround and contain various structures within the body, entirely encircling individual muscles and providing support for nerves, lymphatics, and blood vessels. Some fascial layers, such as the peritoneum, begin to adhere to underlying tissues as soon as movement ceases, which is a trait that has been found in immobilized joints as well (4). Fascia serves to transmit load, provide support, improve nerve conduction, form the architectural borders of various tissues, and allow for the smooth movement between muscle fibers (4, 5).

In an experimental porcine study addressing thoracolumbar fascia injuries, it was found that damage to one area can alter the physiologic properties of others (6). In this study, small (4 × 4-cm) surgical injuries were induced 2 cm lateral to the midline at L3/L4. Half of these patients were then fitted with a hobble that restricted mobility of the rear leg on the ipsilateral side to the injury, and half were allowed to move freely. Control animals had no surgery and no movement restriction. After 8 weeks, ultrasound imaging of 2 cm lateral to the midline at L3/ L4 on the side contralateral to the original injury showed increased thickness in the deep subcutaneous tissue and the perimuscular fascia for all injured animals. They also experienced a significant reduction in thoracolumbar shear strain, which was significantly exacerbated in the movement of restricted subjects.

Cartilage

Articular cartilage is an avascular, alymphatic tissue that provides cushioning within joints and allows for the smooth movement of opposing bones (7). Chondrocytes, which are embedded within the extracellular matrix (ECM), are responsible for the repair and upkeep of the tissue. They do so through the production of materials, such as collagen and proteoglycans, necessary for the strength and durability of cartilage. Water makes up between 65% and 75% of articular cartilage’s weight, which results in high hydrostatic pressure (7). This allows for the transport of nutrients and waste between the cartilage and synovial fluid through simple diffusion and contributes to the strength of the tissue. The ECM is held in a homeostatic balance between the breakdown of older tissues and the production of new tissues during normal conditions. However, acute or chronic stress can induce excess catabolic reactions, leading to degenerative changes on affected tissues (8).

Tendons and Ligaments

Tendons allow for the passive transmission of force from muscles to bones, resulting in movement. They are com-

posed of tendon fibroblasts (sometimes called tenocytes), located within an ECM, which, like the chondrocytes in cartilage, are responsible for the maintenance and healing of the tendon. They manufacture the proteoglycans and collagen necessary to keep the tissue healthy. The tendon’s strength comes from tightly packed collagen fibers in a parallel arrangement that facilitate joint movement and stability (9). Viscoelastic properties combined with high stiffness allows them to react effectively in conditions of both high and low strain because they are capable of storing or transmitting force as needed (9). A low metabolic rate makes it possible for tendons to maintain tension for extended periods of time without being subject to ischemic effects, but this also results in a prolonged healing time in the case of injury (10). Collagen fibers and fibrils have a crimped configuration when not subjected to load, enabling them to elongate under appropriate load without injury (10).

The anatomy of tendons and ligaments is very similar (11). Ligaments contain fibroblasts within an ECM that controls the biological processes of the tissues. Parallel bundles of collagen are the source of the ligament’s high tensile strength, and these fibers are arranged along the long axis of the tissue (12). Unlike tendons, which transmit the force of muscles across joints to move the opposing bone, ligaments cross the joint space to attach bone to bone, providing the necessary stability for movement to occur. Both tendons and ligaments are frequent sources of injury resulting from either trauma or overwork (11).

Mechanoreceptors

Connective tissue cells, such as the fascia, cartilage, tendons, and ligaments, are considered mechanoreceptors that are constantly changing in response to outside stimuli. These mechanoreceptors change the mechanical stimuli into a chemical response that affects the structure and function of the cells (9). Their design helps them operate optimally under their normal physiologic conditions; however, detrimental effects can result from overstimulation or understimulation of the cells (9, 13). As such, the healing of these tissues requires a careful balance between biomechanical stresses and optimal ratios of anabolic and catabolic processes within the ECM (14, 15). The detrimental effects of joint immobilization have been shown to affect not only the joint itself but the extraarticular tissues as well (9, 16, 17). Joint capsule contracture, cartilage surface degeneration, hypertrophic capsular changes, adhesion formation between synovial folds and articular cartilage, and increased deposition of incongruous collagen fibers, with subsequent loss of normal AHVMA Journal • Volume 63 Summer 2021

range of motion (ROM), are some of the changes that have been documented (a) (16, 18). Other changes attributed to immobilization include but are not limited to the following:

• Decrease in cartilage density, thickness, stiffness, shear properties, and glycosaminoglycan levels (19, 20).

• Decrease in the gene expression of aggrecan, a vital protein involved in withstanding compressive forces in cartilage (21). • In tendons, a significant delay in load to failure restoration, decreased stiffness, and the development of fibrocartilage dispersed between fiber bundles (17).

In a study comparing outcomes of fixed versus hinged distraction of the human ankle during osteoarthritis treatment, the hinged distraction group showed decreased pain and disability compared with the fixed distraction group (22). These chemical and morphologic changes emphasize the importance of movement to the overall health of intraarticular and periarticular connective tissues (22). Loss of strength and/or function in cartilage tissue began within 4 weeks (19). Therefore, we can surmise that healing of joints injured from trauma or surgery may be slowed down by restricting movement and the gravitational stress of normal function (4, 9, 10, 12, 15, 16). The tissue degradation caused by immobilization is very similar to that of osteoarthritis, and some of the damage, such as joint contracture, may require surgery to correct (20, 23). As such, it is important to take these considerations into account when looking at the postinjury or postsurgical period of healing (24). Strict cage rest may result in deterioration of important structural components, such as tendons, joint capsules, and cartilage, in the patient’s body (16, 18, 20).

One of the primary causes of cartilage damage is inflammation because proinflammatory cytokines (such as interleukin 1β [IL-1β] and tumor necrosis factor α [TNF-α]) cause the production of collagenases, which degrade the ECM (25). Inflammatory cytokines also down-regulate the production of tissue inhibitors of metallopeptidase, resulting in further catabolism of the ECM (25). Other proinflammatory enzymes, such as inducible nitric oxide synthase, cyclooxygenase 2, and matrix metalloproteinase 1, are factors in the breakdown of the ECM and cartilage as a whole (24). In order to understand how to maintain cartilage health or to restore function after an injury, it is necessary to understand the factors, such as forced immobility, that may exacerbate the inflammatory response, 46

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leading to the potential for increased damage and delayed healing (20, 25).

Passive range of motion (PROM) has been shown to act as an anti-inflammatory therapy, reducing matrix metalloproteinase 1 (MMP1), cyclooxygenase 2 (COX-2), and IL-1β, and the degradation of glycosaminoglycans (Figure 1) (26). Compressive forces have been shown to act as antagonists to TNF-α, thereby suppressing the aforementioned enzymes responsible for the destruction of cartilage tissue and stopping the down-regulation of proteoglycan synthesis (25). In an additional study, a dynamic compressive force within physiologic frequencies provided by a cellstraining apparatus inhibited the release of nitrous oxide and prostaglandin E2 (PGE2) (27).

Figure 1

PROM exercise of right shoulder joint and elbow joint, with the goal of avoiding joint contracture and adhesion formation. It will also initiate an anti-inflammatory response within the joint and aid in the reduction of connective tissue matrix catabolism. Abbreviation: PROM, passive range of motion.

Physical Rehabilitation Research has shown the importance of a controlled and gradual increase in physical activity when there has been an injury to the types of connective tissues discussed in this paper (24, 28-31). A study published in 2018 showed that a single hydrotherapy session improved ROM and stride lengths not only in the dogs with elbow dysplasia that were the intended target population but in the control group as well (28). Another published article involving dogs with painful or restricted movement caused by

Figure 2 several diagnosed orthopedic conditions began with a period of enforced rest for all patients. This resulted in no positive changes in the dogs’ conditions. Next, they were divided into a control group and a treatment group. An analysis of variance (ANOVA)-validated feedback was used to document improvement as the owner compared the ability to walk, trot, jump, and rise from a lying position after the first treatment. This analysis showed improvement in the treated group as compared to the control group. Eight days after their second treatment, there was an increase in play behavior and more ease going downstairs in the treated group as compared to the control group (29). Early rehabilitative therapies, such as PROM, appropriate weight-bearing exercises, transcutaneous electrical nerve stimulation (TENS), neuromuscular electrical stimulation (NMES), and massage, can prevent many damaging catabolic changes in tissues that may have a long-term effect on the patient’s musculoskeletal health (Figure 2, Figure 3) (24).

A 2008 published article discussed canine subjects that underwent an experimental injury and repair of their flexor digitorum profundus tendons. One group was allowed to be weight-bearing, and the other was not. All other therapy was identical (PROM for 5 minutes/ day). At 21 days, the weight-bearing group showed better healing than the non–weight-bearing group, with significantly improved ROM and tendon excursion (30). In healthy human subjects, regular, weightbearing training has been shown to increase collagen type I synthesis in the Achilles tendon over the course of several weeks by initiating a catabolic/anabolic turnover process that replenished collagen faster than it was broken down (31). Additional evidence of the metabolic benefits of weight-bearing and movement has been shown in mice tendons. After doing moderate exercise training for 3 weeks, researchers compared the quantity and activity of tendon stem cells, which are essential components for maintaining homeostasis and repair in the tissues. In this study, the population doubling time of the tendon stem cells was approximately half of what it was in the control group (mice free to wander at will in their cage), with significantly higher collagen production. In addition, patellar tendons averaged 70% higher collagen content in the experimental group, and the Achilles tendon had a 200% increase in collagen content (32).

In research published in 2002, surgical transection of the medial collateral ligaments of mice was performed, followed by recovery during which one group was

Rear limb perturbations with elevated front limbs, which will initiate gentle loading onto the pelvic limbs to begin anti-inflammatory cytokine production and reduce the loss of connective tissue integrity during the healing process. This exercise can be done without forelimb elevation when necessary.

Figure 3

Active ROM exercise of hip joints, used to combine loading and mobility to avoid joint contracture and adhesions, initiate an anti-inflammatory response through the use of loading, reduce or prevent further muscle loss, and improve integrity and function of connective tissues. This type of exercise is not usually appropriate for patients immediately postinjury but can often be introduced slowly as healing progresses. Abbreviation: ROM, range of motion.

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allowed to ambulate freely. In a second group, the hind legs were suspended through a noninvasive tail suspension protocol. A third group underwent sham surgery. Tissues were collected and compared after 3 and 7 weeks. Evaluation of the tissues from animals in the suspension group revealed increased adhesions, abnormal scar formation, and disorganized deposition of collagen fibers in the ligaments; softer and more fragile long bones; and delayed healing of the surgical incision as compared to the tissues from the animals in the ambulatory group. The suspension group also showed a reduction of maximum force, ultimate stress, and elastic modulus in comparison to the ambulatory and control groups (33). These findings indicate that movement and weight-bearing are essential for proper healing in these tissues. The strict restriction of stress is likely to result in less-than-optimal healing outcomes that have been described previously.

Overloading

The external stress placed on injured tissue must be appropriate for the phase of healing; otherwise, it has the potential to cause more damage than improvement (15). A biomechanical force that is of high magnitude, such as enforced running to the point of exhaustion, is proinflammatory, which can increase damage and exacerbate an already compromised condition (12, 31). This force results in a traumatic effect on the joint, which can contribute to the development and exacerbation of osteoarthritis, increased joint instability, and breaking down the ECM more rapidly than it regenerates, leaving the tissue more vulnerable to further injury (7). Mechanical stress beyond normal physiologic range has been shown to result in tendon stem cells differentiating into non-tenocytes, reducing the collagen production and therefore the loadbearing abilities of the tissue (32). It is imperative to understand that the type of exercise being executed must be safe and appropriate for the patient’s condition at every stage of healing.

Conclusion

This information emphasizes that physical rehabilitation and controlled exercise are important factors for the maintenance and recovery of connective tissue injuries. Patients who are denied the opportunity to move and bear weight are at a disadvantage and are less likely to return to their full, preinjury strength. During rehabilitation of an injured limb, it is important to consider the whole body. As discussed, lack of exercise itself is a type of injury to the connective tissues, and this is not restricted to the injured limb alone. Consideration must be given to the health and stability of the patient’s entire body, not just a single injured area; therefore, the results of a 48

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reduction in exercise on all of the tissues need to factor into a treatment protocol.

For optimal tissue healing to be achieved, it is important to find a properly trained therapist who understands the stages of healing (34). The therapist must also frequently assess the patient to determine the appropriate progression of exercises based on the phase of tissue recovery. This latter knowledge, coupled with the understanding of any current comorbidities, would provide the patient the best chances for recovery, returning to function, and overall improvement of treatment outcome. Weight control, endocrine dysfunctions, age, sex or reproductive stage, and physical conformation are other factors to consider when developing a sound treatment protocol. This is one of the reasons a one-size-fits-all approach, such as a printout of exercises given at discharge, may not be the most effective means of treatment. Every patient is an individual that much be approached as such, and the therapist working with that animal needs to understand how each of these factors will need to be addressed in their protocol. Endnote a. Cramer G. The clinical anatomy of spinal manipulative therapy, VSMT Post Graduate Certification Proceedings, Module II, 2021, 1-13, Healing Oasis Wellness Center, Sturtevant, WI.

References 1. Bordoni B, Escher AR, Tobbi F, Pranzitelli A, Pianese L. Fascial nomenclature: update 2021, part 1. Cureus. 2021;13(2):e13339. doi:10.7759/cureus.13339 2. Bordoni B, Myers T. A review of the theoretical fascial models: biotensegrity, fascintegrity, and myofascial chains. Cureus. 2020;12(2):e7092. doi:10.7759/cureus.7092

3. Fascial nomenclature. Fascia Research Society website. ht t ps://fasciaresearchsociet y.org/fascial-nomenclat ure. Published 2021. Accessed March 3, 2021. 4. Van der Wal J. The architecture of the connective tissue in the musculoskeletal system: an often overlooked functional parameter as to proprioception in the locomotor apparatus. Int J Ther Massage Bodywork. 2009;2(4):9-23. doi:10.3822/ijtmb.v2i4.62

5. Langevin HM, Huijing PA. Communicating about fascia: history, pitfalls, and recommendations. Int J Ther Massage Bodywork. 2009;2(4):3-8. doi:10.3822/ijtmb.v2i4.63 6. Langevin HM, Fox JR, Koptiuch C, et al. Reduced thoracolumbar fascia shear strain in human chronic low back pain. BMC Musculoskelet Disord. 2011;12(1):203. doi:10.1186/1471-2474-12-203

7. Ulrich-Vinther M, Maloney MD, Schwarz EM, Rosier R, O’Keefe RJ. Articular cartilage biology. J Am Acad Orthop Surg. 2003;11(6):421-430. doi:10.5435/00124635-200311000-00006

8. Francisco V, Pérez T, Pino J, et al. Biomechanics, obesity, and osteoarthritis. The role of adipokines: when the levee breaks. J Orthop Res. 2018;36(2):594-604. doi:10.1002/jor.23788

9. JH Wang, Guo Q, Li B. Tendon biomechanics and mechanobiology: a minireview of basic concepts and recent advancements. J Hand Ther. 2012;25(2):133-40; quiz 141. doi:10.1016/j.jht.2011.07.004 10. Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006;6(2):181-190. 11. Asahara H, Inui M, Lotz MK. Tendons and ligaments: connecting developmental biology to musculoskeletal disease pathogenesis. J Bone Miner Res. 2017;32(9):1773-1782. doi:10.1002/jbmr.3199 12. Frank CB. Ligament structure, physiology and function. J Musculoskelet Neuronal Interact. 2004;4(2):199-201.

13. Knobloch TJ, Madhavan S, Nam J, Agarwal S Jr, Agarwal S. Regulation of chondrocytic gene expression by biomechanical signals. Crit Rev Eukaryot Gene Expr. 2008;18(2):139-150. doi:10.1615/CritRevEukarGeneExpr.v18.i2.30

22. Saltzman CL, Hillis SL, Stolley MP, Anderson DD, Amendola A. Motion versus fixed distraction of the joint in the treatment of ankle osteoarthritis: a prospective randomized controlled trial. J Bone Joint Surg Am. 2012;94(11):961-970. doi:10.2106/ JBJS.K.00018 23. Born CT, Gil JA, Goodman AD. Joint contractures resulting from prolonged immobilization: etiology, prevention, and management. J Am Acad Orthop Surg. 2017;25(2):110-116. doi:10.5435/ JAAOS-D-15-00697 24. Millis DL. Getting the dog moving after surgery. J Am Anim Hosp Assoc. 2004;40(6):429-436. doi:10.5326/0400429

25. Long P, Gassner R, Agarwal S. Tumor necrosis factor alphadependent proinflammatory gene induction is inhibited by cyclic tensile strain in articular chondrocytes in vitro. Arthritis Rheumatol. 2001;44(10):2311-2319. doi:10.1002/ 1529-0131(200110)44:10<2311::AID-ART393>3.0.CO;2-Q 26. Ferretti M, Srinivasan A, Deschner J, et al. Antiinflammatory effects of continuous passive motion on meniscal fibrocartilage. J Orthop Res. 2005;23(5):1165-1171. doi:10.1016/j.orthres.2005.01.025

14. Buckwalter JA. Activity vs. rest in the treatment of bone, soft tissue and joint injuries. Iowa Orthop J. 1995;15:29-42.

27. Chowdhury TT, Bader DL, Lee DA. Dynamic compression counteracts IL-1 beta-induced release of nitric oxide and PGE2 by superficial zone chondrocytes cultured in agarose constructs. Osteoarthritis Cartilage. 2003;11(9):688-696. doi:10.1016/ S1063-4584(03)00149-3

16. Sasabe R, Sakamoto J, Goto K, et al. Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model. J Orthop Res. 2017;35(9):1998-2006. doi:10.1002/jor.23498

29. Lane DM, Hill SA. Effectiveness of combined acupuncture and manual therapy relative to no treatment for canine musculoskeletal pain. Can Vet J. 2016;57(4):407-414.

15. Killian ML, Cavinatto L, Galatz LM, Thomopoulos S. The role of mechanobiology in tendon healing. J Shoulder Elbow Surg. 2012;21(2):228-237. doi:10.1016/j.jse.2011.11.002

17. Palmes D, Spiegel HU, Schneider TO, et al. Achilles tendon healing: long-term biomechanical effects of postoperative mobilization and immobilization in a new mouse model. J Orthop Res. 2002;20(5):939-946. doi:10.1016/S0736-0266(02)00032-3

18. Cramer GD, Henderson CN, Little JW, Daley C, Grieve TJ. Zygapophyseal joint adhesions after induced hypomobility. J Manipulative Physiol Ther. 2010;33(7):508-518. doi:10.1016/ j.jmpt.2010.08.002 19. Narmoneva DA, Cheung HS, Wang JY, Howell DS, Setton LA. Altered swelling behavior of femoral cartilage following joint immobilization in a canine model. J Orthop Res. 2002;20(1):83-91. doi:10.1016/S0736-0266(01)00076-6

20. Leroux MA, Cheung HS, Bau JL, Wang JY, Howell DS, Setton LA. Altered mechanics and histomorphometry of canine tibial cartilage following joint immobilization. Osteoarthritis Cartilage. 2001;9(7):633-640. doi:10.1053/joca.2001.0432

21. Djurasovic M, Aldridge JW, Grumbles R, Rosenwasser MP, Howell D, Ratcliffe A. Knee joint immobilization decreases aggrecan gene expression in the meniscus. Am J Sports Med. 1998;26(3):460-466. doi:10.1177/03635465980260032101

28. Preston T, Wills AP. A single hydrotherapy session increases range of motion and stride length in Labrador retrievers diagnosed with elbow dysplasia. Vet J. 2018;234:105-110. doi:10.1016/j.tvjl.2018.02.013

30. Thomopoulos S, Zampiakis E, Das R, Silva MJ, Gelberman RH. The effect of muscle loading on flexor tendon-to-bone healing in a canine model. J Orthop Res. 2008;26(12):1611-1617. doi:10.1002/ jor.20689

31. Zhang J, Wang JH. Production of PGE(2) increases in tendons subjected to repetitive mechanical loading and induces differentiation of tendon stem cells into non-tenocytes. J Orthop Res. 2010;28(2):198-203. doi:10.1002/jor.20962 32. Zhang J, Pan T, Liu Y, Wang JH. Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC-related cellular production of collagen. J Orthop Res. 2010;28(9):1178-1183. doi:10.1002/jor.21123

33. Provenzano PP, Martinez DA, Grindeland RE, Dwyer KW, Turner J, Vailas AC, et al. Hindlimb unloading alters ligament healing. J Appl Physiol (1985). 2003;94(1):314-324. doi:10.1152/ japplphysiol.00340.2002 34. Shaw KK, Alvarez L, Foster SA, Tomlinson JE, Shaw AJ, Pozzi A. Fundamental principles of rehabilitation and musculoskeletal tissue healing. Vet Surg. 2020;49(1):22-32. doi:10.1111/vsu.13270 AHVMA Journal • Volume 63 Summer 2021

From The Literature

Quantitative Translation of Dogto-Human Aging by Conserved Remodeling of the DNA Methylome Wang T, Ma J, Hogan AN, et al. Quantitative translation of dog-to-human aging by conserved remodeling of the DNA methylome. Cell Syst. 2020;11(2):176-185.e6. [PMC free article]

Reviewed by Bernard M. Fischer, DVM, PhD Editorial Committee

For years people have estimated that a year in a dog’s life equated to 7 human years. However, this manuscript describes a new method to gauge a dog’s age compared to humans. The authors compared dogs, mice, and humans to see if their findings apply across mammalian species. They investigated a type of DNA science called epigenetics. Epigenetic modifications of the DNA occur when methyl groups are found on some cytosine-guanine dinucleotides, termed methyl-CpGs. This does not occur in all DNA areas and will occur more frequently in some areas of the DNA than others. The authors evaluated the DNA methylome of 104 Labrador retrievers between the ages of 0 and 16 years. There were approximately 20 dogs less than 2 years of age and 5 dogs between 14 and 16. Most other 2-year age ranges had 10-15 dogs per group. To analyze the DNA methylome, the authors used a method called syntenic bisulfite sequencing for the canine genome and mapped this to the Illumina 450K methylation array of humans to create whole-genome alignments between dogs and humans. The prior publication of the canine genome and collaboration with members of the canine genome team from the National Human Genome Research Institute at the National Institutes of Health enabled the whole-genome methylation comparison between species. The authors evaluated cytosine-guanine methylation in over 7900 genes for which orthologs, homologous genes Table 1. Dog to Human age comparison Time period Description Juvenile Adolescent Mature Senior

Infancy until just before puberty Puberty to completion of growth Subsequent period until life expectancy

AHVMA Journal • Volume 63 Summer 2021

in different species that catalyze the same reaction, were present in humans, dogs, and mice. They identified 394 genes that demonstrated conserved time-dependent methylation across species. They mapped these genes to biological networks which were predominately development related: anatomical developmental 1 and 2, leukocyte differentiation and metabolic pathways, neuroepithelial cell differentiation, and synapse assembly and regulation. Most of these networks demonstrated increased methylation with age, though leukocyte differentiation and nucleic-acid metabolism primarily demonstrated decreasing methylation with age. The authors showed that the developmental gene pathways were critical networks for calculating dogto-human methylome similarity. Ultimately, the epigenetic clock described provides a nonlinear transformation from dog-to-human age, as shown in Table 1.

Collectively, these results demonstrate that the methylome can be used to translate the age-related physiological changes experienced by an individual, animal or human, and relate it to the physiology of a second mammalian species. The methylome may also serve as a diagnostic measure for a single species or across species as it relates to aging changes. The hope is that this research will provide a new tool for evaluating therapeutic interventions for maximizing a healthy life span for any mammalian species.

Dog age 2-6 months 6 months-2 years 2-7 years 7-12 years and up

Human age 1-12 years Approximately 12-25 years 25-50 years 50-70 years and up

From The Literature

Origins and Genetic Legacy of Prehistoric Dogs Bergström A, Frantz L, Schmidt R, et al. Origins and genetic legacy of prehistoric dogs. Science. 2020;370:557-564.

Of Dogs and Men Pavlidis P, Somel M. Of dogs and men. Science. 2020;370(6516):522-523.

Reviewed by Kristy Herman, DVM Editorial Committee

Dog: man’s best friend, considered to be the first domesticated species. As we learn more about the complexities of genetics and our technology improves to help further our research, more questions can be asked and answered. We have long believed dogs to be descended from wolves, but what more can be learned? Scientists have looked at the past for clues that can help us understand our faithful friends on a more personal level. Bergström et al. sequenced 27 ancient dog genomes up to 10,900 years old from Europe, the Near East, and Siberia to shed light on dog population history. To look for a correlation with human population history, 17 sets of human genomewide data matching the ancient dog age, geographic location, and cultural context were assessed, and genetic relationships were compared between the 2 species. It was discovered that at least 5 major ancestry lineages had diversified by 11,000 years ago, indicating that global dog population structure has Pleistocene origins, and it is likely that all dogs derive from a single ancient, now-extinct wolf population (or closely related wolf populations). No detectable evidence was found for multiple dog origins or extensive gene flow from wild canids, and gene flow was likely unidirectional from dogs to wolves.

Pavlidis and Somel discuss the Bergström et al. study, highlighting the diversity and spread of dog lineages and its interconnectedness with human populations. Genetic relations between human populations are comparable to dog populations in Eurasia and the Americas, suggesting similar patterns of movement between humans and dogs.

To illustrate this discovery, nearly half of the ancestry of European dogs originates from Paleolithic West Eurasia, whereas the other half originates from Southwest Asia; modern-day Europeans are largely descended from preNeolithic hunter-gatherers and Neolithic farmers from Anatolia. This similarity is not straightforward, however; decoupling has occurred over time as humans and dogs traveled their separate ways. In Neolithic and Chalcolithic Iran, people have remained, but indigenous dogs have been replaced by Levantine dogs. Interestingly, similarities have been found between dog and human evolutionary adaptation, namely, in the variation in the copy number of genes encoding amylase. Compared to chimpanzees, humans have extra salivary amylase that is believed to correspond with the increase in starch consumption that may have begun before farming. Compared to wolves, dogs also carry extra pancreatic amylase copies, which can aid in starch digestion. Arctic sled dogs were found to have genetic signature of adaption in their fatty acid metabolism genes, also found in the adaptive changes in the metabolic pathways of the local Inuits, most likely connected to the high-fat Arctic diet. By comparing dog and human populations, it is possible to study genetic composition and its changes across time, land, and species. Future research on dog-like fossils can help us learn more about the origins of dog domestication, which may ultimately lead to the discovery of additional examples of convergent evolution between dogs and humans. Long withstanding the test of time, it is unlikely the bond between humans and dogs will be broken any time soon. AHVMA Journal • Volume 63 Summer 2021

From The Literature

Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence Hart BL, Hart LA, Thigpen AP, Willits NH. Assisting decision-making on age of neutering for 35 breeds of dogs: associated joint disorders, cancers, and urinary incontinence. Front Vet Sci. 2020;7:388. [Open Access]

Summary by W. Jean Dodds, DVM Editorial Committee

Neutering male and female dogs in the first 6-12 months of life is routinely performed in the United States and Europe. This can increase risks for some common cancers and debilitating joint diseases, as shown in a previous study on Golden Retrievers, Labrador Retrievers, and German Shepherd Dogs which demonstrated that neutering prior to 1 year of age produced a 2- to 4-fold increase in joint disorders. To expand on that data, 15 years of computerized records from the Veterinary Medical Teaching Hospital, University of California, Davis were analyzed for an additional 32 canine breeds and varieties. Wide variations were noted in the categories of breed, size, gender, and age of neutering (if performed) on the risks of hip dysplasia, cruciate ligament disease, elbow dysplasia, and cancers such as lymphoma, mast cell tumors, hemangiosarcoma, and osteosarcoma. For instance, the 11 small breeds surveyed showed no increase in joint disorders as compared to larger breeds. In 2 giant breeds, the Great Dane and Irish Wolfhound, no increase in joint disorders was noted with neutering at any age. Although neutered dogs of both sexes are reported to be more likely to die from cancer, the study found that in small breeds, only the Boston Terrier and Shih Tzu had any significant increase in cancer risk when neutered. Sex differences were found in the Boston Terrier, as neutering females at 6 months old did 52

AHVMA Journal • Volume 63 Summer 2021

not increase the risk of joint disorders or cancer, but neutering males prior to 1 year of age did increase cancer risk. In Cocker Spaniels the opposite gender effect was seen, as females had a 17% increased cancer risk if neutered before age 2 years, while no increase was seen in males neutered at 6 months old. Neutering female Golden Retrievers at any age produced a 2- to 4-fold increase in cancers.

For varieties within breeds, male Standard Poodles neutered at 1 year of age had a 6-fold higher cancer risk, mainly for lymphosarcoma. By contrast, in Miniature Poodles no increase in cancers was noted with neutering, but joint disorders were significantly increased in individuals neutered at 6-11 months old.

This evidence-based study is well worth reading, as it provides guidelines which can be consulted in order to choose the best age for neutering each patient. Overall, only a relatively few dog breeds have an elevated risk for joint disorders and cancers when neutered as compared to being left intact. Two limitations of the study were noted. First, a relatively small number of breeds was available for inclusion in large enough numbers for statistical evaluation compared to the total number of dog breeds. Second, there was a lack of information regarding the reasons that neutering was or was not chosen.

From The Literature

Efficacy of Wu Mei Wan for Treating Equine Metabolic Syndrome Related Laminitis and Uveitis Poorly Responsive to Conventional Medicine Lankenau CJ. Efficacy of Wu Mei Wan for treating equine metabolic syndrome related laminitis and uveitis poorly responsive to conventional medicine. Am J Trad Chin Vet Med. 2019;14(2):31-44.

Reviewed by Nancy Scanlan, DVM Editorial Committee

Abbreviations

Equine metabolic syndrome (EMS) has parallels with human metabolic syndrome, including the fact that signs can be variable. As in humans, the symptom picture in equines includes obesity, increased regional adiposity (especially at the neck crest and tailhead regions in equines), insulin resistance accompanied by basal hyperinsulinemia, a general pro-inflammatory state, and vascular dysfunction. Unlike humans, serum blood glucose is not usually elevated. In the equine, inflammation and vascular dysfunction lead to laminitis and uveitis in extreme cases, whereas cardiac and/or cerebrovascular disease is commonly seen in humans. However, some Shetland ponies have been reported to also exhibit left ventricular hypertrophy with increased blood pressure and heart rate as part of EMS.

to the percentage of eye closure, from 0 (not at all) to 4 (completely shut). The uveitis must have been present and unresponsive to treatment for more than 30 days. All conventional treatments were allowed during the study, including the use of NSAIDs, isoxsuprine, deep bedding, supportive hoof care, and diet restrictions for laminitis; and topical steroids, atropine, antibiotics and oral NSAIDs for uveitis.

EMS with laminitis and/or uveitis matches the Chinese pattern of Jue Yin syndrome, which is characterized by symptoms of both Heat and Cold related to the upper body and the gastrointestinal tract and involving the organs and areas described in Traditional Chinese Medicine as Pericardium, Heart, and Middle Burner. Wu Mei Wan is a classical Chinese herbal formula used to treat Jue Yin level diseases. This study tested the effects of Wu Mei Wan in 24 patients diagnosed with Jue Yin syndrome. The group consisted of equines with intractable EMS, for whom conventional therapy was not effective and who were being considered for euthanasia. Among these horses, 16 had laminitis alone, 4 had uveitis alone, and 4 had both laminitis and uveitis.

Both conventional Western and traditional Chinese medical examinations were conducted. The degree of lameness from laminitis was graded from 0 (not at all lame) to 5 (minimal weight bearing in motion and/or at rest or a complete inability to move). Uveitis was graded according

EMS

Equine metabolic syndrome

Patients were evaluated when first enrolled and weekly thereafter, for a total of 5 evaluations. All subjects received oral administration of Wu Mei Wan granules (7 g per 454 kg body wt PO, BID, for 30 days) during the study. Improvement was calculated each week by comparing the weekly score to the initial pre-treatment score.

The mean score for lameness in the horses with laminitis began at 3.85 +/- 0.88 (mean +/- standard deviation). At the end of 4 weeks, the mean decreased to a range of 0 to 0.41, with 18 of 20 horses showing no lameness at all and 2 horses scoring a 1 on the pain scale. Uveitis scores began at a mean of 3.25 +/- 0.89 and ended with a mean ranging from 0 to 0.895. It is interesting to note that the scores for laminitis improved each week, while the uveitis score improvements plateaued after 2 weeks.

Wu Mei Wan consists of 10 individual herbs. In addition to being anti-inflammatory, analgesic, and/or antioxidative, research has shown that these herbs have various metabolic or cardiovascular benefits. These benefits include improvements in lipid regulation, plasma lipid profiles, and insulin sensitivity; reduced hepatic lipidosis; and reduced body weight. Some of the constituents of Wu Mei Wan show an ability to affect platelet aggregation and blood vessel dilation, improve cardiac function, and protect against cardiac hypertrophy. AHVMA Journal • Volume 63 Summer 2021

From The Literature

Trace Element Levels in Serum Are Potentially Valuable Diagnostic Markers in Dogs Cedeňo Y, Miranda M, Orjales I, et al. Trace element levels in serum are potentially valuable diagnostic markers in dogs. Animals (Basel). 2020;10(12):2316. [Open Access]

Reviewed by Lea Stogdale, DVM Editorial Committee

Trace elements are essential components of nutrition, affecting numerous biochemical processes in the body. Significant diseases caused by deficiencies and excesses of trace elements are well documented in humans, livestock, and dogs (1). It has been previously documented that animals in oxidative stress during critical illness have low serum levels of selenium (Se) and zinc (Zn). However, it is not known whether the decreased levels are the result of the inflammatory response, lowered intake or absorption, or alterations in distribution by changes in protein-binding transportation or cellular shifts. It is also unknown whether the changes in mineral levels contribute to organ damage (2).

In this study, the authors report on the evaluation of trace element profiles in various diseases in dogs. They attempt to associate serum trace element levels with the pathogeneses and diagnoses. The trace elements included copper (Cu), molybdenum (Mo), Se, and Zn. In addition to normal dogs (n = 42), they sampled dogs with acute or chronic liver (n = 25), intestinal (diarrhea) (n = 24), inflammatory (n = 24), and kidney (n = 22) diseases. The methodology was valid. The statistical analyses were multidimensional and mathematically complex (dendrograms from squared Euclidean distance and Ward agglomerative method). Of the 7 serum biochemical parameters reported, there were consistent significant increases in alanine aminotransferase and alkaline phosphatase in liver disease, urea nitrogen and creatinine in kidney disease, and globulins in inflammatory and renal diseases. Neither albumin nor glucose was significantly altered in this sample of dogs. Correlations were made between Cu and globulins, Mo and creatinine, and Se, Zn, and albumin, all irrespective of the diagnosed disease. The fact that serum Cu levels were higher in dogs with liver disease is interesting. However, we already know these levels are variable in their reliability to indicate nutritional 54

AHVMA Journal • Volume 63 Summer 2021

status because they are tightly controlled by homeostatic regulation, changing little despite varying dietary intake (3). Also, serum Cu levels are not indicative of liver copper storage excess (4-6). Increased levels are expected in inflammatory disorders because Cu is mainly transported by ceruloplasmin, a component of globulins (3).

Although the authors conclude that the results confirm their hypothesis that trace elements are significant in the pathogenesis of some diseases, the data presented only shows that the serum levels of the 4 reported minerals (Cu, Mo, Se, and Zn) are altered in the profiled diseases. This publication does not show a cause or effect or significance of altered trace mineral levels in serum.

The authors also conclude that serum trace mineral analyses, along with the standard biochemical tests, could provide “valuable information” for the diagnosis and prognosis of some diseases in dogs. However, this publication provides no evidence that a serum trace mineral profile provides any diagnostic advantage over the standard biochemical profile. There was no evidence relating to prognosis. References

1. National Research Council. Nutrient requirements of dogs and cats. The National Academies Press; 2006.

2. Mertens K, Lowes DA, Webster NR, et al. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br J Anaesth. 2015;114(6):990-999. doi:10.1093/bja/aev073 3. Harris ED. The transport of copper. Prog Clin Biol Res. 1993;380:163-179.

4. Michigan State University, Veterinary Diagnostic Laboratory. Minerals in tissue, fixed tissue, & water. Accessed January 6, 2020. https://tinyurl.com/MSU-MineralDiagnostics

5. Strickland JM, Buchweitz JP, Smedley RC, et al. Hepatic copper concentrations in 546 dogs (1982-2015). J Vet Intern Med. 2018;32(6):1943-1950. doi:10.1111/jvim.15308 6. Talcott PA. Copper. In: Peterson ME, Talcott PA, eds. Small animal toxicology. 3rd ed. Saunders; 2013:517-521.

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AHVMA Journal • Volume 63 Summer 2021

Saturday, October 2, 2021 6:50am- 7:40am

Exhibitor Hosted Breakfast Meetings

Vendor Hosted Breakfast Meeting- Ziwi 7:00am – 7:30am

Morning Meditation

8:00am – 8:10am

Announcements

PT EQUINE MASTERCLASS

AHVMA/ INTRO TO CAVM

ENERGY OF LIFE

TCVM

***PRELIMINARY PROGRAM - SUBJECT TO CHANGE - PLEASE VISIT WWW.AHVMA.ORG FOR UPDATES*** 8:10am-9:00am

Intro to Holistic Veterinary Medicine -Doug Knueven

9:10am- 10:00am

10:00am- 10:45am 10:45am-11:35am

11:50am- 12:40pm

Forelimb Asymmetries in the Energy of Life: Our Equine Athlete Quantum Connection

TCVM for Wei Syndrome

Raw Food Revolution 1

-Pedro Rivera Rear Limb Asymmetries in the Equine Athlete

-Susan Wagner -Ronald Koh Energy Medicine: Techniques TCVM for Urinary for Pets & Vets Incontinence

-Doug Knueven

-Pedro Rivera

-Susan Wagner

Raw Food Revolution 2

Functional Neuroanatomy in Animals as Mirrors for Equine Back Pain Dis-Ease

-Doug Knueven

-Ronald Koh

Break in Exhibit Hall

-Pedro Rivera -Susan Wagner Keynote- Doug Knueven- Holistic Renewal

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TCVM for Fecal Incontinence -Ronald Koh

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Intro to Veterinary Spinal Upper Body Lameness: Manipulative The Forequarters

Connection Between ECS & Nervous System

TCVM for Vestibular Syndrome

-Pedro Rivera Basics of a Complete Neuro Exam

-Deborah Marshall Upper Body Lameness: Balance & Hindquarters

-Susan Wagner The ECS & GI Systems: A Critical Connection

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-Pedro Rivera

-Deborah Marshall Exhibit Hall Break

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How to Approach Patients with IPS & MSI

Upper Body Lameness: Evaluation & Treatment

The Importance of ECS for Treating Pain

TCVM for Inflammatory CNS Diseases

-Pedro Rivera

-Deborah Marshall

-Susan Wagner

-Ronald Koh

AHVMA Journal • Volume 63 Summer 2021

Reception in the Exhibit Hall

Sunday, October 3, 2021 6:50am- 7:40am

Exhibitor Hosted Breakfast Meetings

Vendor Hosted Breakfast Meeting- Healthy Hemp Vendor Hosted Breakfast Meeting- Multi Radiance Vendor Hosted Breakfast Meeting- Wellsong Vendor Hosted Breakfast Meeting- VetClassics 7:00am- 7:30am

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What You Learned About Introduction to Herbal Thyroid Disorders was Wrong Medicine -Deborah Mitchell -W. Jean Dodds

Integrative Tools to Calm the Cytokine Storm -Janet Gordon Palm

Exhibit Hall Break

9:00am- 9:45am 9:45am- 10:35am

Make Joints Feel & Move Better -Laurie McCauley

Salivary Diagnostics Direct Introduction to Veterinary Manual Therapy Lab Dietary Therapy Acupuncture Session 1 -Deborah Mitchell (2 hours) -W. Jean Dodds

10:45am- 11:35am Evolving Vaccine Technology, Integrating Holistic Efficacy & Safety Medicine into your -W. Jean Dodds Practice -Deborah Mitchell 11:35am-1:10pm

-Laurie McCauley

Perioperative Applications of Nonthermal Laser -Janet Gordon Palm Photobiomodulation and NRF2

*space limited, -Janet Gordon Palm registration required

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Exhibitor Hosted Lunch & Learn Meetings

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Bioactive Lipids to Address The Brain on Fire -Ann- Margaret Morgan

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Remove Oral Masses with Homeopathy -Martha Lindsay Feline Asthma- Blown Away with Homeopathy -Martha Lindsay Exhibit Hall Break

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Homeopathy for Hyperthyroidism with Renal Disease -Martha Lindsay

Cocktail Reception

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*space limited, registration required

What Happens in Vagus Doesn’t Stay in Vagus -Janet Gordon Palm The Feline Enrichment: Missing Link in 5 Freedoms -Janet Gordon Palm

Taking the MS Exam to Photobiomodulation from a Whole New Level Prehab to Rehab -Laurie McCauley

-Janet Gordon Palm

AHVM Foundation Silent Auction- **All donations benefit STUDENTS interested in Holistic Medicine** Banquet- ** ticketed event- you must present your banquet ticket to enter**

AHVMA Journal • Volume 63 Summer 2021

Monday, October 4, 2021 6:50am- 7:40am

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Basics of Iridology, Window of the Soul

Mem-Brain, Bystander or Initiator

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Creating a 21st Century Integrative Practice

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Thermal Imaging in Vet Practice -Ronald Riegel Use of IRT in Integrated Companion Animal Practice -Ronald Riegel Use of Infrared Thermography in Equine Practice -Ronald Riegel

Trends & Challenges to Heart Coherence: Pillar 1 of Canine/Feline Tui-Na Lab Veterinary Wellbeing CALM (2 hours) -Laurie Fonken -Allen Schoen -Suzan Seelye Healthy People Healthy Mind Body Medicine *space limited, Practice Coherence: Pillar 2 of registration required CALM -Laurie Fonken -Allen Schoen Exhibit Hall Break Integration: Life, Work & Trans-species & Unified Wellbeing Field Coherence: Pillar 3

-Laurie Fonken -Allen Schoen Memorial Celebration- Time & Location TBD

Chinese Tui-Na- A Manual Therapy -Suzan Seelye

Tuesday, October 5, 2021 7:00am- 7:30am

Morning Meditation

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Announcements

ONE HEALTH HERBAL MEDICINE LARGE MEDICINE

AYUVEDA

END OF LIFE

***PRELIMINARY PROGRAM - SUBJECT TO CHANGE - PLEASE VISIT WWW.AHVMA.ORG FOR UPDATES***

8:10am-9:00am

Treating Infectious Disease with Herbs -Nancy Martin

9:10am-10:00am

Equine Lymphatic System and TCVM -Nancy Martin

Intro to Ayurvedic Principles

Helping Owners Assess Quality of Life

-Ava Frick

-Mary Gardner

Ayurveda- Vata Dosha

5 Elements of Hospice

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-Mary Gardner

10:00am-10:15am 10:15am-11:05am

Break Plant Medicine Powerhouses -Nancy Martin

11:15am-12:05pm

Ayurveda- Pitta Dosha

Mapping the Euthanasia Experience- Part 1

-Ava Frick

-Mary Gardner

Rantimicrobial Resistance & Ayurveda- Kapha Dosha Food Safety -Ava Frick -Nancy Martin

Mapping the Euthanasia Experience- Part 2 -Mary Gardner

2021 AHVMA ANNUAL CONFERENCE PRELIMINARY PROGRAM Continuing Education Updates This program “2021 AHVMA Annual Conference” will be submitted for approval by AAVSB RACE. AHVMA will also be applying for continuing education approval from individual state boards, as well as our many allied organizations. Over the past five years, (2016 through 2020) AHVMA has received RACE approval for approximately 90% of our Annual Conference lecture and lab content. Please visit www.ahvma.org for program and continuing education updates. AHVMA is a member of the AVMA House of Delegates. Many states grant blanket approval for AVMA affiliate organizations.

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HEALTHY HEMP MULTI RADIANCE WELLSONG VETCLASSICS

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IVAS

AVH

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EXHIBITOR HOSTED LUNCH & LEARN MEETINGS

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ADD-ONS

EXHIBITOR HOSTED BREAKFAST MEETINGS SATURDAY

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**TOTAL** .................................................................$ CANCELLATION POLICY Cancellations received up to July 3, 2021 • Full Refund (less $50 admin fee) Received between July 3 - August 15, 2021• 50% Refund Cancellations after August 15, 2021 or No Shows • No Refund

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All conference attendees and exhibitors should beware of ANY individual who calls and claims to be a representative of AHVMA or the host hotel. AHVMA does NOT solicit conference registrants directly for hotel bookings, nor do we request credit card numbers over the phone for room reservations. Please book your conference hotel rooms safely and securely through the AHVMA Website group block link at: https://www.ahvma.org/hotel-and-travel/

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JAHVMA #63–2021

*** ALERT: HOTEL ROOM BOOKING SCAMS.

P R E

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Card Holder Signature fax, email, or mail BOTH pages of completed registration with payment to the AHVMA office. Pre-registration closes on AUGUST 15, 2021

Food & Beverage Disclaimer - AHVMA and our host hotel will make every effort to accommodate dietary restrictions;

however, there is no guarantee that we will be able to accommodate all food intolerances/special diets. Please let AHVMA know of any food allergies at the time of your registration. AHVMA Journal • Volume 63 Summer 2021 63

www.ahvma.org

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AHVMA

202 1 membersh i p

A P P LI C AT I ON

A me r i c a n H o l i s ti c Ve te r i nar y Medi cal A ssoci at i on

202 1- 2 0 2 2 M e m b e r s h i p Fo r m - D u e s Ye a r Be g in s Ap ril 1 st a n d e n d s Ma rc h 3 1 st th e Fo llo w in g Ye ar submit completed application

name/details last first

middle

date of birth (mm/dd/yy)

gender

educational info

male female unspecified

complete educational information required for all non-subscriber memberships

Fax: 410.569.2346

veterinary medical college (college/school if technician)

Any questions? Please contact AHVMA at 410.569.0795

other degree(s)/certification(s)

veterinary degree

Mail: American Holistic Veterinary Medical Association PO Box 630 Abingdon, MD 21009

email:office@ahvma.org

veterinary graduation date (mm/yy)

AHVMA Members should be aware that professional memberships, certifications and other credentials (such as CVC, CVH, CVCH) are the intellectual property of the certifying organization and misuse is not permitted. It is not the responsibility of AHVMA to verify any certifications or memberships, etc. claimed by a member or prospective member. Potential misuse will be referred to the certifying organization for appropriate action.

contact info

please complete all sections. choose your preferred mailing address (for AHVMA mailing) and REFERRAL LISTING (for public online directory)

home address (check if preferred mailing address)

business (check if preferred mailing address) clinic/organization name

address

** *

city

address

state/postal code

city

country

state/postal code country

cell

home phone PREFERRED email

phone

(required for login)

online directory listing

home

business

none

do not include my information in member mailing list

fax

DIRECTORY email

include corresponding phone in REFERRAL DIRECTORY #

(this will be visible online)

only full members are included in AHVMA “Find a Vet” referral directory

membership categories

I am a NEW member, please send me a new member packet.

Member Veterinarian .................................................. $232 Graduate Veterinarians, graduated 2017 or before.

Retired/Inactive non-voting (non-AVMA)....................$110 Formerly a Regular Member for at least 15 consecutive years and is now fully retired from practice, and wishes to continue to receive AHVMA Journal.

I was referred by: AVMA Info

Retired/Inactive voting (AVMA Member)...................... $55

I AM an AVMA member. AVMA #:

Formerly a Regular Member for at least 15 consecutive years and is now fully retired from practice who is an AVMA Member, and who wishes to receive the AHVMA Journal.

I am not an AVMA member.

Academia ....................................................................... $55 College or University Faculty member who wishes to receive the AHVMA Journal.

First Year Graduate (2020) ....................... Complimentary Second Year Graduate (2019) .................. Complimentary Third Year Graduate (2018) ........................................ $100 Veterinary Student .................................... Complimentary Must provide Dean’s letter or veterinary student ID as proof of current enrollment in AVMA accredited school.

SAHVMA Advisor ....................................... Complimentary Faculty Advisor to an organized National SAHVMA Chapter.

Veterinary Technician/Support Staff ........................... $80 Subscriber ..................................................................................... $95

other organizations please list other veterinary associations/organization of which you are a member: State Veterinary Association:_____________________________

AHVMA ASSOCIATE MEMBERSHIP Businesses or non-profit organizations directly related to the Mission of AHVMA. Not available for veterinary clinics, hospitals or practicing veterinarians. Includes business listing in online Associate Directory. Contact us for application and list of benefits!

TOTAL Dues (and donation if applicable) ........................... $ name on card

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AHVMA Journal • Volume 63 Summer 2021

JAHVMA #63–2021

Online journal only.

I would like to DONATE to SAHVMA ............................... $ (Student AHVMA)

AHVMA

online ref e r r a l

D I R E C TO RY

A m e r i c a n H o l i s t i c Ve t e r i n a r y M e d i c a l A s s o c i a t i o n

The AHVMA Office maintains an online referral directory for Member Veterinarians, which lists all contact information and modalities practiced. It is available to the public online at www.ahvma.org. If you are a Licensed Practicing Veterinarian who currently utilizes at least one holistic modality, are accepting new clients, and would like to be included in our referral directory, we request that you complete the form below. The accuracy of the information provided is your responsibility. If any of your information changes, you must submit a new form or update your profile online. Dues must be current by April 1st each year to remain on the directory, though we allow a 30-day grace period before your listing is removed. Please type or print CLEARLY. Fill in all information you wanted listed in the directory. Remember, this is referral information, so the contact information you give should be related to your business (in other words, don’t list your home address or phone number unless you want it in the directory.). Check all of the “Practice Type” and “Modalities Used” categories that apply to you. referral directory name

phone

clinic name

fax

address

email state/province

city

zip/postal

www.ahvma.org small animal

practice type

country

website exotic

equine

avian

large animal

house calls

modalities used Acupuncture

Herbs, Chinese

Ozone Therapy

certification (check all that apply)

Herbs, Western

Prolotherapy

Glandular Therapy

Pulsating Magnetic Therapy

Homeopathy

Reiki

Chi Inst

CuraCore

IVAS

Other:

Applied Kinesiology

Veterinary NAET

(check all that apply)

Aromatherapy

Classical

Bach Flower Remedies

Veterinary Orthopedic Manipulation

AVH Certified

Homotoxicology

Chiropractic certification (check all that apply)

Immuno-Augmentive Therapy

AVCA

Laser Therapy

HOWC

Other:

Clinical Nutrition

Magnetic Therapy

Optional Information

Color Therapy

Massage Therapy

Do you have any Board Certifications?

Conventional Medicine

Nutraceuticals

If yes, please list:

Essential Oils

Nutrition

Flower Essences

Osteopathy

AHVMA Member Benefits

Your membership pays for itself. AHVMA dues are approximately 100% return on investment for each client referral.

In addition to inclusion in the AHVMA online referral directory Member Veterinarians receive the following benefits:

submit completed application

• Deeply Discounted Registration to AHVMA Conferences

Mail: American Holistic Veterinary Medical Association PO Box 630 | Abingdon, MD 21009

• Representation in the AVMA House of Delegates **You will be required to log in to access benefits below** • Access to Natural Standards Database (over a $200 value) • Members-only webpages • Unlimited Online Access to JAHVMA

(Journal of the American Holistic Veterinary Medical Association) • Annual Conference Proceedings

(includes access to archived proceedings)

• AHVMA e-Newsletters • AHVMA Member Vets in the contiguous US receive discounted titer testing from the Kansas State University Veterinary Diagnostic Lab (KSVDL).

Fax: 410.569.2346 | Phone:410-569-0795 | Email:office@ahvma.org

Save the Dates

AHVMA2022

JAHVMA #63–2021

CSU

September 10 - 13 Hilton West Palm Beach West Palm Beach, FL

AHVMA is a 501(c)(3) organization. Your dues and donations may be tax deductible; please check with your accountant.

AHVMA Journal • Volume 63 Summer 2021

ACVBM and VBMA Update

ACVBM and VBMA: What's the Difference? By Cynthia Lankenau, DVM

Despite the travel restrictions and limitations encountered this past year, both the VBMA (Veterinary Botanical Medicine Association) and the ACVBM (American College of Veterinary Botanical Medicine) have been remarkably busy with virtual conferences and webinars. We are often asked to explain the difference between the VBMA and the ACVBM. The VBMA is an organization that welcomes any veterinarian with an interest in botanical medicine, regardless of experience. Members range from those with extensive prior training in herbal medicine to those with no training at all. The VBMA also has many wonderful members holding the RH(AHG) degree. These are the American Herbalists Guild’s Registered Herbalists, non-veterinarian professional herbalists who bring a wealth of knowledge into our group. The VBMA holds three to four educational webinars each year and hosts an annual conference. Our first webinar in 2021, “How to Integrate Herbs into Your Practice," was a panel discussion by the VBMA board. As a means to increase our membership and outreach, we created a unique opportunity for existing VBMA members: purchase the webinar and receive a free webinar invitation to share with a non-member. Our next webinar will be given by Dr. Shen Xie on equine protozoal myeloencephalitis (EPM), Wednesday, June 16, 2021, at 8:00 pm EDT.

This year's VBMA conference will be held during the International Herbal Symposium. We have a fantastic line-up for everyone. It will be held virtually, but with this venue participants will be able to listen to all lectures. We will be featuring Constance DiNatale, DVM, CVA, speaking on Chinese food therapy. Her lectures will explore food from a 5-element 66

AHVMA Journal • Volume 63 Summer 2021

context and provide participants a greater understanding of food indications. Dr. DiNatale will also give a four-hour intensive on ways to incorporate herbs into the diets of small animals. Cindy Lankenau, DVM, will present lectures on metabolic syndrome as well as FIP and their relationship to COVID. Gary Richter, DVM, will give lectures on herb-drug interactions and herbs and mushrooms for the cancer patient, and he will offer a cannabis intensive. Alexia Tsakiris, BVetMed, GDipVWHM, CVA, RH (AHG), will speak on the topics of grief and alpacas with exhausted adrenals. We will present tentative ideas for an eco-tour in 2022— Alaska is a potential destination. Visit www.vbma.org for details. The ACVBM is an organization working to ensure that any veterinarian can progress toward diplomate status in botanical medicine. Our goal is to receive AVMA recognition for botanical medicine as a board specialty. While working toward this goal, we need to develop a solid group of herbally-trained veterinarians who meet a diplomate level of expertise in botanical medicine and can serve as advisors in future residency programs. We also need to encourage and develop ethical and humane herbal research to demonstrate the scientific basis for our uses of herbal medicines. Additionally, we are in the process of encouraging enrollment in current botanical medicine veterinary programs and plan to develop further educational opportunities for those interested in achieving diplomate status. Our website is being developed as a source of information and reference material for any veterinarian. We gladly accept anyone’s input and help in these projects, including the development of additional white papers on the use of various botanical medicines, drug-herb interactions, and antibiotic resistance. Our virtual conference will be held this October; speakers and dates are pending. Stay tuned at www.acvbm.org.

Council of Elders

The Sharing of Wisdom By Twila Floyd, DVM

As veterinarians, we place a high value on promoting our patients’ wellness and relieving them from discomfort and pain. From childhood, we desired to care for and help injured animals. We learned various talents, skills, and secrets from our parents, grandparents, and others to improve the health of helpless creatures. This special desire spurred our pursuit for further knowledge of husbandry and custodial care. Then, we gratefully accepted our role as promising veterinary students and later as veterinarians, the caretakers of the animals. Upon entering the “real world” of veterinary medicine, we honed our craft from veterinary school mentors and wiser elders in practice who shared with us their skills and judgment gained from years of patient, unbiased clinical experience. They passed the baton to us, as we sought to achieve their level of talent and wisdom, and hopefully to follow in their paths. What is our role in passing hard-earned wisdom to others? In the real world, how does one achieve wisdom and when do we know we have succeeded?

As new veterinarians, we accepted the traditional practice protocols of vaccines, antibiotics, and surgery, as well as other ways to relieve suffering. Many veterinarians, those just starting out and those in practice for decades, accepted these conventional protocols, while others nurtured an intellectual desire for additional avenues.

Amazingly, our exploration led us to integrative or holistic care. We chose not to place aside our “basket of knowledge” from our mentors and relatives, from older veterinarians in the trenches of practice, and from the teachings of our formal veterinary education. Rather, additional doors of learning opened to our inquiring minds, helping us develop complementary avenues of therapy for our patients. A strong desire to improve our skills, knowledge, and judgment is paramount for all veterinarians. It could be said that wisdom is the attitude leading to action. Our sense of duty as veterinarians is to be mindful that our expertise has been acquired through various pathways of learning. This accumulated wisdom must be shared. For the new veterinarian, the beginning steps of the “caretaker of the animals” are to listen, to observe, to accept the inevitable blunders, and to acquire the good judgment to restore health. And over time, the “baton of wisdom” passes along again, for the betterment of new caretakers and their animal patients.

For support and wisdom, the Council of Elders is here for you. Connect with Council of Elders members listed at www.ahvma.org/committees. Once pandemic restrictions are lifted, speak with attendees at the AHVMA Conferences and attend an annual Healer Heal Thyself Retreat. Wisdom is hard-earned and easily shared. Reach out to a COE member today. AHVMA Journal • Volume 63 Summer 2021

Classifieds

EMPLOYMENT OPPORTUNITIES CALIFORNIA Bird Rock Animal Hospital is located in South La Jolla, CA, a couple of blocks from the ocean. We are looking for one or two integrative veterinarians to join our growing team, practicing with Dr Karen Marsden. (Medical Director). If interested, please send your resume to: Info@BirdRockAH.com. Phone: 858.459.3279 www.BirdRockAH.com

MAINE Island Falls Animal Health Clinic is looking for a veterinarian to join our busy, one doctor practice. Island Falls is located in beautiful, rural, northern Maine. We practice both conventional

and alternative medicine, utilizing TCM, homeopathy, nutraceuticals, and more. We have a stellar reputation, with folks driving over two hours to come to us. Our employees are treated like family. Our clients are treated with compassion. When people cannot afford the gold standard, we get creative and find an affordable treatment that will work. If you love the wilderness and want to make a difference for the better in this world, if you are creative, can think outside the box and want to help others, if you want to be treated with respect and have fun at your job, give us a call. Partnership for the right person is a possibility! Let's talk! Email Dr Jean at IFAHC@protonmail.com or call 207-249-8646.

PRACTICES FOR SALE MARYLAND Practice for sale in the Columbia, MD area —provides both holistic and western services. This is a busy practice with a good client base and a great location. The owner will help with the transition for a smooth step into ownership. Simmons Mid-Atlantic 888-881-7084 or www.SimmonsInc.com — practice MD609.

CLARK COUNTY, NEVADA Well-Established and Profitable! This SA practice offers conventional and holistic medicine in a +/- 2,400 sf leasehold facility in an active shopping plaza. Currently open five

days a week. A new owner could expand hours and services, increasing gross income. NV3 Contact: PS Broker. 800-636-4740. www.psbroker.com. info@psbroker.com

PENNSYLVANIA Small but very busy integrative practice offering holistic and alternative medicine including Chinese Herbs, homeopathy, holistic, and routine veterinary medicine, vaccines, surgery, and dentistry. Limited large animal with great potential. The only clinic in area offering alternative services. Located in a pleasant small town close to Erie, PA. Turnkey. Owner wants to retire. Home phone: 716-252-6535; Email: papavet8@gmail.com

EVENTS 2021 AHVMA ANNUAL CONFERENCE & EXHIBITION When: October 2-5, 2021 Where: Reno, Nevada — Peppermill Resort & Hotel Registration Information: www.ahvma.org/2021-conference-registration/

For information and rates on Classifieds listings please contact office@ahvma.org

AHVMA Journal • Volume 63 Summer 2021

Standard Abbreviations Abbreviation 2-D 3-D

Definition 2-dimensional 3-dimensional

A AAHA

American Animal Hospital Association

ACTH

Adrenocorticotropic hormone

Right ear Left ear Adenosine diphosphate Alanine aminotransferase. See SGPT Alkaline phosphatase Analysis of variance Animal and Plant Health Inspection Service Aspartic aminotransaminase. See SGOT Adenosine triphosphate Adenosine triphosphatase American Veterinary Medical Association

AS ADP ALT ALKP ANOVA APHIS AST ATP ATPase AVMA B BCG BID BSA BUN

Bacille Calmette-Guerin Two times a day Bovine serum albumin Blood urea nitrogen

C °C cAMP CBC CDC CFU‡ CNS CPR CSF CT Ci MCi mCi

Degree(s) Celsius Cyclic adenosine monophosphate Complete blood count Centers for Disease Control and Prevention Colony-forming unit Central nervous system Cardiopulmonary resuscitation Cerebrospinal fluid Computed tomography or computed tomographic Curie(s) Microcurie(s) Millicurie(s)

D D Diam DMSO

Day Diameter Dimethyl sulfoxide

Abbreviation DICOM DNA

Definition Digital Imaging and Communications in Medicine Deoxyribonucleic acid

E ECG EDTA EEG eg ELISA EM

Electrocardiogram or electrocardiographic. Also EKG. Ethylenediaminetetraacetic acid Electroencephalogram Latin for for example; use only in parenthetical expressions Enzyme-linked immunosorbent assay Electron microscopy

F °F FDA FeLV FIV

Degree Fahrenheit Food and Drug Administration Feline leukemia virus Feline immunodeficiency virus

G GABA g

Gamma-aminobutyric acid Gram

H h or hr H&E Hct or HCT Hgb or Hb HIV hpf

Hour or hours Hematoxylin and Eosin Hematocrit Hemoglobin Human immunodeficiency virus High-power field or high-power fields

I ie Ig IM IP IU IV

Latin for that is; use only in parenthetical statements Immunoglobulin Intramuscular Intraperitoneal International unit(s) Intravenous

L LD50 L Ml ml

Median lethal dose Liter(s) Mliter(s) Milliliter

AHVMA Journal • Volume 63 Summer 2021

Abbreviation

Definition

m Mm min MLV M mo MRI§ mRNA

Meter micrometer Minutes Modified live virus Molar Month Magnetic resonance imaging Messenger ribonucleic acid

N n NAD+ NADH NADP NADPH No. NO NSAID

Number in a study group Nicotinamide adenine dinucleotide NAD + reduced NAD+ phosphate NADP reduced Number Nitric oxide Nonsteroidal anti-inflammatory drug

O OD

Optical density Right eye Left eye

OD OS P P PET PBS PCR PCV PG PMN PO

Probability Positron Emission Tomography Phosphate-buffered saline Polymerase chain reaction Packed cell volume Prostaglandin Polymorphonuclear leukocytes Per os

Q q

Every Daily or every day or once a day

QD R RBC RIA RNA rpm rRNA

Abbreviation

Red blood cell Radioimmunoassay Ribonucleic acid Revolutions per minute Ribosomal ribonucleic acid

AHVMA Journal • Volume 63 Summer 2021

s SD SE SEM SGOT SGPT SID SSRI SOD SV-40

second Standard deviation Standard error Standard error of the mean Serum glutamic-oxaloacetic transaminase. See AST Serum glutamate pyruvate transaminase. See ALT Once daily Selective serotonin reuptake inhibitor Superoxide dismutase Simian virus 40

T T½ TID tRNA

Half-life Three times a day Transfer ribonucleic acid

U U U.S. or U.S.A.† USDA† UV

Unit United States United States Department of Agriculture Ultraviolet

V V vol

Volt Volume

W W Wk wt WBC

Watt Week Weight White blood cell

Y yr

Year

§Although this abbreviation can be an adjective or a noun, it cannot be used to mean magnetic resonance image. The term MRI image is acceptable.

†The abbreviation US may be used without expansion on first mention only when it is used as a modifier and only when it directly precedes the word it modifies. In other instances, United States should be used.