PAINWeek Journal Vol 8, Q1

vol. 8 q 1 2020

better with age: pain management in the older adult p.18 low back pain! where do we go from here? p.26 putting the “fun” in dysfunctional p1: pain management in renal dysfunction p.36 sleep and pain: friends or foes p.46

PaiNWeeK CONFeReNCe SNaPSHOT P.68

Education moves forward. www.painweek.org

Education is the best analgesic. www.painweek.org

When conventional lidocaine patches don’t stick, do they work?

PROBLEM

PROVEN 12-HOUR ADHESION

SOLUTION

Did you know? HALF of patients surveyed report that other lidocaine patches detach ≥3 times in 12 hours?1*

Only ZTlido® delivers 12-HOUR adhesion in a non-opioid therapy (zee-tee-lie-doh)

VISIT THE SCILEX PHARMACEUTICALS EXHIBIT to see the lidocaine patch reinvented. *According to a 2016 Harris Poll among PHN patients (n=153) and nurses (n=151).

Reference: 1. Harris Poll Conducted Online from May 2-25, 2016. PHN Patients & Nurses Study: Final Report. June 9, 2016. Supported by funding from Scilex Pharmaceuticals Inc.

Indication ZTLIDO is indicated for relief of pain associated with post-herpetic neuralgia (PHN).

Important Safety Information Contraindications ZTLIDO is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

Warnings and Precautions Accidental exposure can occur even after a ZTLIDO patch has been used.

Small children or pets could suffer serious adverse effects from chewing or ingesting a new or used ZTLIDO patch. Store and dispose of patches properly and keep out of reach of children and pets.

Excessive dosing or overexposure to lidocaine can occur. Longer duration of application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increased blood concentration levels of lidocaine. If lidocaine overdose is suspected, check drug blood concentration. Management of overdose includes close monitoring, supportive care, and symptomatic treatment.

Cases of methemoglobinemia have been reported with local anesthetic use, although patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, or concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. Signs and symptoms include cyanotic skin discoloration and/or abnormal coloration of the blood and may occur immediately or may be delayed after exposure.

Methemoglobin levels may continue to rise leading to more serious central nervous system and cardiovascular adverse effects. Discontinue ZTLIDO and any other oxidizing agents. Depending on severity of the symptoms, patients may respond to supportive care or may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

Application site reactions can occur during or immediately after treatment with ZTLIDO. This may include development of blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erythema, exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the locus of abnormal sensation. These reactions are generally mild and transient, resolving spontaneously within a few minutes to hours. Inform patients of these potential reactions and that severe skin irritation may occur with ZTLIDO if applied for a longer period than instructed.

Hypersensitivity cross-reactions may be possible for patients allergic to PABA derivatives. Manage hypersensitivity reactions by conventional means.

Eye exposure with ZTLIDO should be avoided. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye (eg, eye glasses/eye wear) until sensation returns.

Adverse Reactions Side effects of ZTLIDO include application site reactions such as, irritation, erythema, and pruritus. These are not all of the adverse reactions that may occur.

Please see full Prescribing Information for more information.

Use in Specific Populations Use of ZTLIDO during lactation should be used with caution as lidocaine is excreted into breast milk. The limited human data with lidocaine in pregnant women are not sufficient to inform drug-associated risk for major birth defects and miscarriage.

To report SUSPECTED ADVERSE REACTIONS, contact SCILEX Pharmaceuticals Inc. at 1-866-SCILEX3 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Brief Summary of Prescribing Information on following page.

SCILEX® and ZTLIDO® are registered trademarks of SCILEX Pharmaceuticals Inc. All other trademarks are the property of their respective owners. © 2020 SCILEX Pharmaceuticals Inc. All rights reserved. ZTL-00289 01/20

ZTLIDO® (lidocaine topical system) Rx only Brief Summary: This information is not comprehensive. Visit www.ZTlido.com/hcp to obtain the FDA-approved product labeling or call 1-866-SCILEX3 (1-866-724-5393).

INDICATIONS AND USAGE ZTLIDO contains lidocaine, an amide local anesthetic, and is indicated for relief of pain associated with post-herpetic neuralgia (PHN).

DOSAGE AND ADMINISTRATION Apply up to three topical systems only once for up to 12 hours in a 24-hour period.

CONTRAINDICATIONS Contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type, or to any other component of the product.

WARNINGS AND PRECAUTIONS Accidental Exposure Even a used ZTLIDO topical system contains residual lidocaine after use. A small child or pet may suffer serious effects from chewing or ingesting a new or used ZTLIDO. It is important for patients to store and dispose of ZTLIDO properly and keep out of the reach of children, pets, and others.

Excessive Dosing/Overexposure The following may contribute to higher blood concentration of lidocaine, leading to adverse effects: longer duration of application; application of more than the recommended number of ZTLIDO; smaller patients; hepatically impaired patients; use on non-intact skin; or applying heat sources to ZTLIDO. Methemoglobinemia Cases of methemoglobinemia have been reported in association with local anesthetic use. Signs may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Discontinue ZTLIDO and any other oxidizing agents.

Application Site Reactions During or immediately after treatment with ZTLIDO, application site reactions may develop including blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erythema, exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the locus of abnormal sensation. Inform patients that severe skin irritation may occur with ZTLIDO if applied for a longer period than recommended.

Hypersensitivity Reactions Cross sensitivity to ZTLIDO in patients with a history of drug sensitivity to para-aminobenzoic acid (PABA) derivatives is possible.

Eye Exposure Immediately wash out the eye with water or saline and protect the eye until sensation returns.

ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail elsewhere in the labeling: • Methemoglobinemia • Application Site Reactions • Hypersensitivity Reactions

The following adverse reactions from voluntary reports or clinical studies have been reported with lidocaine. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissues: blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erosions, erythema, exfoliation, flushing, irritation, papules, petechia, pruritus, vesicles, and abnormal sensation.

Immune system: angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria.

Central Nervous System: lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, somnolence, respiratory depression and arrest.

Cardiovascular: bradycardia, hypotension, and cardiovascular collapse leading to arrest.

Other: asthenia, disorientation, headache, hyperesthesia, hypoesthesia, metallic taste, nausea, pain exacerbated, paresthesia, taste alteration, and vomiting.

DRUG INTERACTIONS Drugs That May Cause Methemoglobinemia When Used with ZTLIDO Patients who are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drug classes: nitrates/nitrites; local anesthetics; antineoplastic agents; antibiotics; antimalarials; anticonvulsants; other drugs (e.g., acetaminophen, metoclopramide, quinine).

Antiarrhythmic Drugs When ZTLIDO is used in patients receiving Class I antiarrhythmic drugs (such as tocainide and mexiletine), the toxic effects are additive and potentially synergistic. Consider risk/benefit during concomitant use.

Local Anesthetics When ZTLIDO is used concomitantly with other products containing local anesthetic agents, the effects are additive. Consider the amount of drug absorbed from all formulations when local anesthetic agents are administered concomitantly.

OVERDOSAGE Lidocaine overdose from cutaneous absorption is rare but could occur. If there is any suspicion of lidocaine overdose, check drug blood concentration. The management of overdose includes close monitoring, supportive care, and symptomatic treatment. Dialysis is of negligible value in the treatment of acute overdose with lidocaine.

This brief summary is based on ZTLIDO prescribing information revised November 2018. ZTL-00118 01/19 Manufactured for: Scilex Pharmaceuticals Inc. Palo Alto, CA 94303 USA SCILEX® and ZTLIDO® are registered trademarks of Scilex Pharmaceuticals Inc. © 2020 Scilex Pharmaceuticals Inc. All rights reserved.

“Meetings

come to an end, but learning never stops.

PWJ keeps you going all year long.”

—Michael R. Clark md, mph, mba

Executive Editor Kevin L. Zacharoff md, facpe, facip, faap Publisher Painweek Art Director Darryl Fossa Editorial Director Debra Weiner Editor Holly Caster

Editorial Board

Charles E. Argoff md, cpe Professor of Neurology Albany Medical College Department of Neurology Director Comprehensive Pain Center Albany Medical Center Department of Neurology Albany, ny Jennifer Bolen jd Founder Legal Side of Pain Knoxville, tn Martin D. Cheatle PhD Associate Professor Director, Pain and Chemical Dependency Program Perelman School of Medicine University of Pennsylvania Center for Study of Addiction Philadelphia, pa Paul J. Christo md, mba Associate Professor Johns Hopkins University School of Medicine Department of Anesthesiology and Critical Care Medicine Baltimore, md Michael R. Clark MD, MPH, MBA Associate Professor of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore, md Chair of Psychiatry Inova Health System Falls Church, VA

David Cosio PhD, ABPP Psychologist Jesse Brown VA Medical Center University of Illinois at Chicago College of Medicine, Pain Medicine Northwestern Feinberg School of Medicine, Psychiatry and Behavioral Sciences Chicago, il

Srinivas Nalamachu md Clinical Assistant Professor Kansas University Medical Center Department of Rehabilitation Medicine Kansas City, ks President and Medical Director International Clinical Research Institute Overland Park, ks

David M. Glick DC, DAAPM, CPE, FASPE CEO & Medical Director HealthQ2 Richmond, va

Steven D. Passik phd Vice President Scientific Affairs, Education, and Policy Collegium Pharmaceuticals, Inc. Canton, ma

Douglas L. Gourlay MD, MSc, FRCPC, DFASAM Educational Consultant Former Director, Wasser Pain Centre Pain and Chemical Dependency Division Toronto, Ontario Gary W. Jay md, faapm Clinical Professor University of North Carolina Department of Neurology Chapel Hill, nc Jay Joshi MD, DABA, DABA-FM, FABA-FM CEO and Medical Director National Pain Centers Vernon Hills, il Theresa Mallick-Searle MS, NP-BC, ANP-BC Nurse Practitioner Stanford Health Care Division of Pain Medicine Stanford, ca

Joseph V. Pergolizzi md Chief Operating Officer nema Research Inc. Naples, fl Michael E. Schatman phd, cpe, daspe Editor-in-Chief Journal of Pain Research Adjunct Clinical Assistant Professor Tufts University School of Medicine Department of Health & Community Medicine Boston, ma Kathryn A. Schopmeyer PT, DPT, CPE Physical Therapy Program Coordinator Pain Management San Francisco va Healthcare System San Francisco, ca

Mary Lynn McPherson pharmd, ma, mde, bcps Professor and Vice Chair University of Maryland School of Pharmacy Department of Pharmacy Practice and Science Hospice Consultant Pharmacist Baltimore, md

Copyright © 2020, PAINWeek, a division of Tarsus Medical Group.

The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of PAINWeek or its publication staff.

PAINWeek does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. PAINWeek does not assume any responsibility for injury arising from any use or misuse of the printed materials contained herein. The printed materials contained herein are assumed to be from reliable sources, and there is no implication that they represent the only, or best, methodologies or procedures for the pain condition discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and drug dosage information contained herein, and to make modifications as new information arises.

All rights are reserved by PAINWeek to accept, reject, or modify any advertisement submitted for publication. It is the policy of PAINWeek to not endorse products.

Any advertising herein may not be construed as an endorsement, either expressed or implied, of a product or service.

The national conference on pain for frontline practitioners.

2020

SePTeMBeR 8—12

Global Education Group (Global) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education to physicians. Global Education Group designates this live activity for a minimum of 39.0 AMA PRA Category 1 Credit(s)™. This activity will be approved for continuing pharmacy, psychology, nurse practitioner, nursing, and dentistry education. Applications for certification of social work NASW and family physician AAFP hours will be applied for. For more information and complete CME/CE accreditation details, visit our website at www.painweek.org.

vol.8 q1 2020

18 26 36 46 54

geriatric pain management

better with age: pain management in the older adult

by maria c. foy

regional pain sydromes

low back pain! where do we go from here?

by david m. glick

pharmacotherapy

putting the “fun” in dysfunctional ( p1) pain management in renal dysfunction

by courtney m. kominek abigail t. brooks

behavioral pain management

sleep and pain friends or foes?

by fiona barwick heather king

back to basics

the basics of pain treatment ( p2)

by kevin l. zacharoff

59

pw next generation

with peter pryzbylkowski

60 61 62

clinical pearls

by charles e. argoff

one-minute clinician

with tanya j. uritsky, maria c. foy, charles e. argoff, martin cheatle, leigh ann wilson, collin v. montgomery, stephen j. ziegler

64 67

pundit profile

with colleen m. fitzgerald

puzzled?

by wendy caster

pain by numbers

PaiNWeeK CONFeReNCe SNaPSHOT P.68 10

Check out RELISTOR® (methylnaltrexone bromide) For your adult patients with opioid-induced constipation (OIC) 1 MOVANTIK® (naloxegol)

SYMPROIC® (naldemedine)

✓

✓

Indicated for OIC in patients with chronic non-cancer pain (CNCP)1-3

✓

Indicated for OIC in patients with advanced illness (AI) or pain caused by active cancer1-3

✓

Multiple routes of administration1-3

✓

✓

Functions as a peripherally acting mu-opioid receptor antagonist (PAMORA)1-3

✓

✓

✓

✓

No impact on opioid-mediated analgesia1-3

✓

✓

✓

✓

No significant pharmacokinetic drug-drug interactions3-5

✓

✓

✓

Comparison of products does not suggest comparable efficacy and safety or interchangeability. Please consult the full Prescribing Information for all products.

MOVANTIK is a registered trademark of the AstraZeneca group of companies.

SYMPROIC is a registered trademark of Shionogi & Co., Ltd. Osaka, Japan.

INDICATIONS • RELISTOR® (methylnaltrexone bromide) is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

• RELISTOR injection is also indicated for the treatment of OIC in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

IMPORTANT SAFETY INFORMATION • RELISTOR tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

• Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases).

Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

• If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

RELISTOR: The only product in its class...

• With both oral and subcutaneous routes of administration1 • With no significant pharmacokinetic drug-drug interactions5 • With multiple FDA-approved indications1-3 Comparison of products does not suggest comparable efficacy and safety or interchangeability. Please consult the full Prescribing Information for all products. * Study 4 was a multicenter, double-blind, randomized, placebo-controlled study; 154 patients with AI and opioid-induced constipation (OIC) received a single subcutaneous dose of RELISTOR injection or placebo. Sixty-two percent of adult patients with AI taking RELISTOR injection experienced a spontaneous bowel movement (SBM) within 4 hours of the first dose vs 14% for placebo (P<.0001).1,6 † Study 5 was a 2-week, multicenter, double-blind, randomized, placebo-controlled trial followed by a subsequent 3-month, open-label extension study. The efficacy of RELISTOR was evaluated in 133 patients. Forty-eight percent of adult patients with AI taking RELISTOR injection experienced an SBM within 4 hours of the first dose vs 16% for placebo (P<.0001).1,7 ‡ In a 4-week, randomized, multicenter, double-blind, placebo-controlled, phase 3 study, the efficacy of RELISTOR tablets was evaluated in 401 patients (200 RELISTOR tablets, 201 placebo) with CNCP for which they were taking opioids. All patients had OIC, defined as <3 SBMs per week and at least one additional symptom of constipation. SBM was achieved within 4 hours in 27% of dosing days for adult patients with CNCP taking RELISTOR tablets vs 18% for placebo (P<.0001).1,4,5

IMPORTANT SAFETY INFORMATION (cont’d) • Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal.

• Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

• The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

• A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment.

• A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions and dose adjust per Prescribing Information as may be indicated.

• In the clinical studies, the most common adverse reactions were: OIC in adult patients with chronic non-cancer pain • RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%).

• RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%).

OIC in adult patients with advanced illness • RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%), flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%).

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Brief Summary of Prescribing Information on the following page.

REFERENCES: 1. RELISTOR [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals. 2. Movantik [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP. 3. Symproic [prescribing information]. Raleigh, NC: BioDelivery Sciences International, Inc. 4. Michna E, Blonsky ER, Schulman S, et al. Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic nonmalignant pain: a randomized controlled study. J Pain. 2011;12(5):554-562. 5. Data on file. Clinical study report MNTX3201. Salix Pharmaceuticals; 2015. 6. Slatkin N, Thomas J, Lipman AG, et al.

Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. J Support Oncol. 2009;7(1):39-46. 7. Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008;358(22):2332-2343. www.salix.com 400 Somerset Corporate Boulevard, Bridgewater, NJ 08807 Tel 800-321-4576 Relistor is a trademark of Salix Pharmaceuticals or its affiliates. ©2019 Salix Pharmaceuticals or its affiliates.

REL.0201.USA.19

BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use RELISTOR safely and effectively. See full prescribing information for RELISTOR. RELISTOR (methylnaltrexone bromide) 150 mg tablets, for oral use.

RELISTOR (methylnaltrexone bromide) injection, for subcutaneous use.

8 mg/0.4 mL methylnaltrexone bromide in single-dose pre-filled syringe.

12 mg/0.6 mL methylnaltrexone bromide in a single-dose pre-filled syringe, or single-dose vial.

Initial U.S. Approval: 2008 INDICATIONS AND USAGE Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.

Opioid-Induced Constipation in Adult Patients with Advanced Illness or Pain Caused by Active Cancer RELISTOR injection is indicated for the treatment of OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

CONTRAINDICATIONS RELISTOR tablets and injection are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

WARNINGS AND PRECAUTIONS Gastrointestinal Perforation Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

Severe or Persistent Diarrhea If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Opioid Withdrawal Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain The safety of RELISTOR tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 12-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR tablets 450 mg orally (200 patients) or placebo (201 patients). After 4 weeks of double-blind treatment administered once daily, patients continued 8 weeks of double-blind treatment on an as needed basis (but not more than once daily).

The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR tablets are shown in Table 4.

Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

Table 4: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Tablets in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 1) RELISTOR Tablets Placebo Adverse Reaction n = 200 n = 201 Abdominal Pain** 14% 10% Diarrhea 5% 2% Headache 4% 3% Abdominal Distention 4% 2% Vomiting 3% 2% Hyperhidrosis 3% 1% Anxiety 2% 1% Muscle Spasms 2% 1% Rhinorrhea 2% 1% Chills 2% 0%

*Adverse reactions occurring in at least 2% of patients receiving RELISTOR tablets 450 mg once daily and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness

The safety of RELISTOR injection was evaluated in a double-blind, placebocontrolled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 2) included a 4-week, doubleblind, placebo-controlled period in which adult patients were randomized to receive RELISTOR injection 12 mg subcutaneously once daily (150 patients) or placebo (162 patients). After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR injection 12 mg subcutaneously was administered less frequently than the recommended dosage regimen of 12 mg once daily.

The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR injection are shown in Table 5. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.

Table 5: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Injection in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 2) RELISTOR Injection Placebo Adverse Reaction n = 150 n = 162 Abdominal Pain** 21% 7% Nausea 9% 6% Diarrhea 6% 4% Hyperhidrosis 6% 1% Hot Flush 3% 2% Tremor 1% <1% Chills 1% 0%

*Adverse reactions occurring in at least 1% of patients receiving RELISTOR injection 12 mg subcutaneously once daily and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness During the 4-week double-blind period, in patients with OIC and chronic non-cancer pain that received RELISTOR every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily RELISTOR dosing. Use of RELISTOR injection 12 mg subcutaneously every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 2) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%).

The safety of RELISTOR injection was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with OIC and chronic non-cancer pain (Study 3). Patients were allowed to administer RELISTOR injection 12 mg subcutaneously less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48-week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 2. Additionally, in Study 3, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR. Opioid-Induced Constipation in Adult Patients with Advanced Illness The safety of RELISTOR injection was evaluated in two, double-blind, placebo-controlled trials in adult patients with OIC and advanced illness receiving palliative care: Study 4 included a single-dose, double-blind, placebo-controlled period, whereas Study 5 included a 14-day multiple dose, double-blind, placebo-controlled period.

The most common adverse reactions in adult patients with OIC and advanced illness receiving RELISTOR injection are shown in Table 6 below.

Table 6: Adverse Reactions from All Doses in Double-Blind, PlaceboControlled Clinical Studies of RELISTOR Injection in Adult Patients with OIC and Advanced Illness* (Studies 4 and 5) RELISTOR Injection Placebo Adverse Reaction n = 165 n = 123 Abdominal Pain** 29% 10% Flatulence 13% 6% Nausea 12% 5% Dizziness 7% 2% Diarrhea 6% 2%

*Adverse reactions occurring in at least 5% of patients receiving all doses of RELISTOR injection (0.075, 0.15, and 0.3 mg/kg) and at an incidence greater than placebo **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness The rates of discontinuation due to adverse reactions during the double-blind, placebo-controlled clinical trials (Study 4 and Study 5) were comparable between RELISTOR (1%) and placebo (2%).

Postmarketing Experience The following adverse reactions have been identified during post-approval use of RELISTOR injection. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Gastrointestinal Perforation, cramping, vomiting.

General Disorders and Administration Site Disorders Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported.

DRUG INTERACTIONS Other Opioid Antagonists Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

Drugs Metabolized by Cytochrome P450 Isozymes In healthy subjects, a subcutaneous dose of 0.3 mg/kg of RELISTOR did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate.

USE IN SPECIFIC POPULATIONS Pregnancy The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise pregnant women of the potential risk to a fetus.

Lactation Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use Safety and effectiveness of RELISTOR tablets and injection have not been established in pediatric patients.

Geriatric Use In clinical studies of RELISTOR tablets, no overall differences in effectiveness were observed. Adverse reactions were similar; however, there was a higher incidence of diarrhea in elderly patients.

In clinical studies of RELISTOR injection, no overall differences in safety or effectiveness were observed between elderly patients and younger patients.

Based on pharmacokinetic data, and safety and efficacy data from controlled clinical trials, no dosage adjustment based on age is recommended. Monitor elderly patients for adverse reactions.

Renal Impairment In a study of subjects with varying degrees of renal impairment receiving RELISTOR injection subcutaneously, there was a significant increase in the exposure to methylnaltrexone in subjects with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault) compared to healthy subjects.

Therefore, a dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment.

No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment (creatinine clearance greater than 60 mL/minute as estimated by Cockcroft-Gault).

Hepatic Impairment Tablets In a study of subjects with varying degrees of hepatic impairment receiving a 450 mg dose of RELISTOR tablets, there was a significant increase in systemic exposure of methylnaltrexone for subjects with moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment compared to healthy subjects with normal hepatic function. Therefore, a dosage reduction of RELISTOR tablets is recommended in patients with moderate or severe hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A).

Injection There was no clinically meaningful change in systemic exposure of methylnaltrexone compared to healthy subjects with normal hepatic function. No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions.

OVERDOSAGE A study of healthy subjects noted orthostatic hypotension associated with a dose of 0.64 mg/kg administered as an intravenous bolus. Monitor for signs or symptoms of orthostatic hypotension and initiate treatment as appropriate.

If a patient on opioid therapy receives an overdose of RELISTOR, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis or reversal of central analgesic effect.

NONCLINICAL TOXICOLOGY Carcinogenesis Oral administration of methylnaltrexone bromide at doses up to 200 mg/kg/day (about 81 times the subcutaneous maximum recommended human dose (MRHD) of 12 mg/day based on body surface area) in males and 400 mg/kg/day (about 162 times the subcutaneous MRHD of 12 mg/day) in females and in Sprague Dawley rats at oral doses up to 300 mg/kg/day (about 243 times the subcutaneous MRHD of 12 mg/day) for 104 weeks did not produce tumors in mice and rats.

Mutagenesis Methylnaltrexone bromide was negative in the Ames test, chromosome aberration tests in Chinese hamster ovary cells and human lymphocytes, in the mouse lymphoma cell forward mutation tests and in the in vivo mouse micronucleus test.

Impairment of Fertility Methylnaltrexone bromide at subcutaneous doses up to 150 mg/kg/day (about 122 times the subcutaneous MRHD of 12 mg/day; about 3.3 times the oral MRHD of 450 mg/day) was found to have no adverse effect on fertility and reproductive performance of male and female rats.

Animal Toxicology and/or Pharmacology In an in vitro human cardiac potassium ion channel (hERG) assay, methylnaltrexone caused concentration-dependent inhibition of hERG current.

PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

For more information, go to www.Relistor.com or call 1-800-321-4576.

Based on 9493104 11/2018 Salix Pharmaceuticals 400 Somerset Corporate Blvd.

Bridgewater, NJ 08807 USA www.salix.com

Manufactured for:

Under license from:

Progenics Pharmaceuticals, Inc. Tarrytown, NY 10591 U.S. Patent Information: For Injection: U.S. Patent Numbers: 8,247,425; 8,420,663; 8,552,025; 8,822,490; 9,180,125; 9,492,445 and 9,669,096 For Tablets: U.S. Patent Numbers: 8,420,663; 8,524,276; 8,956,651; 9,180,125; 9,314,461; 9,492,445 and 9,724,343 Relistor is a trademark of Salix Pharmaceuticals or its affiliates.

REL.0082.USA.19

A quite valuable addition to the content of this article is the inclusion of convenient tables of frequently used pain medications and considerations for their use in this special patient population.

does not occur in a vacuum, Kevin L. Zacharoff and I’m always a bit befuddled when people refer to it as if it does. There are so many dimensions related to the narrative of someone in pain that they are too numerous to count. Most, if not all, of us reflexively think about pain rating A good example of the complex interaction between pain and daily life by as the metric because that’s what we’ve been taught (if we’ve been lucky Drs. Fiona Barwick and Heather King focuses on the intimate relationship enough to have been taught about pain and its management at all), or between sleep and pain. While we may often think that pain prevents most we think it’s the best measurement we have available. The International patients from getting adequate sleep, the authors point out that much more Association for the Study of Pain states that pain is both a sensory and significantly the lack of sleep actually has a greater impact on chronic pain emotional experience. I would posit that chronic pain is actually much more and how it is perceived. Scientific research is discussed that supports the than that—that it is a potentially life-altering experience that can impact bidirectional and reciprocal relationship of pain and sleep, pointing towards patients in an infinite number of ways depending on the specific context the value of cognitive behavioral therapy targeting insomnia as an important of their lives. This is the reason why pharmacologic management related to part of the treatment regimen in managing pain. I think you’ll find the conpain ratings ends up being just one small part of the much bigger picture of clusions of this article and the proposed integrated protocol for comorbid pain management. Let’s have a look at how the articles in the current issue pain and sleep interesting and relevant to your clinical practice. coincide with this logic.

This issue’s Pundit Profile spotlights Dr. Colleen Fitzgerald. Desiring to be Interestingly and not surprisingly, there is also an intimate relationship a doctor since childhood, Colleen approached that goal in life like a train on between the calendar and the pain experience. Dr. Maria Foy provides a rail. Once she chose the path of Physical Medicine & Rehabilitation, she an in-depth analysis of pain and aging, specifically pointing out consider- further focused her career on caring for women in pain. As someone deeply ation of potential adverse effects related to typical pharmacologic treat- involved with educating healthcare providers of the future, she is proud of ment options. We are also provided with a rationale for how pain can be her contributions towards helping women suffering with pelvic pain, and life-altering in this special (and sometimes disparate) patient population. looking forward to making more of them better. Enjoy this window into Special attention is paid to how the context of pain may be different in what drives her and keeps her grounded. elderly patients, due to changes in metabolic function, baseline activity levels, or ability to communicate, or some combination of these and Dr. Peter Pryzbylkowski is the focus of this issue’s Next Generation. Two other common age-related changes. From the pain assessment process things about this interventional pain physician particularly resonate with to treatment plan formulation and follow-up, keep this piece as a handy me: the book that influenced him the most is one of my favorites, and he is resource to help provoke thinking about the narrative of chronic pain in a sucker for any Rocky movie. In my opinion Rocky is one of the most amazing fictional characters of all time. Dr. Pryzbylkowski probably has much in older individuals. common with you as well, so have a look at his profile and get to know this My favorite sentence in our next article by Dr. David Glick is “There is no future thought leader. perfect universal examination.” Much in line with my introduction above, Dr. Glick is elegantly making the point that when it comes to the assess- Also, worthy of mention in this issue of PWJ is my second installment of ment of a patient with chronic low back pain, “every patient is a study of the recurring segment titled Back to the Basics for people seeking basic one.” Chronic low back pain is probably considered to be the most prevalent foundational pain education. type of chronic pain in the US today. Here we are presented with a rational approach to assessment and treatment that takes us far away from the I hope you enjoy this issue, and I’m sure you’ll see that one of it’s common simplistic response to a numerical pain rating; an approach that includes themes is the need to dig much deeper when it comes to adequately consideration of possible comorbidities, underlying pathology, and above all, assessing and treating people with chronic pain. One of my go-to catchcontext. This article does a good job of reminding us that at the center of all phrases is that “We are all the same animal,” something I believe to be true we do is one thing: the patient. Thoughtful and individualized application of both professionally and personally. But it’s also very important for us to remember that our patients are unique individuals as well. knowledge, tools, and skillsets may be the best thing we can do.

Next up is an article by Drs. Courtney Kominek and Abigail Brooks, exploring how the relationship between physiology, renal function, and pharmacology can further complicate the context of chronic pain and its treatment.

Reading this made me think of things we may not often consider that track back to our basic science education, things like volume of distribution, pharmacokinetics, and pharmacodynamics. The most common medications used to treat chronic pain are explored through the lens of caring for patients with chronic kidney disease, with the intention of making sure that patients receive the safest and most efficacious treatment possible.

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Kevin L. Zacharoff MD, FACIP, FACPE, FAAP

Kevin L. Zacharoff is Faculty and Clinical Instructor at suny Stony Brook School of Medicine in New York, and is Ethics Committee Chair at St Catherine of Siena Medical Center in Smithtown, New York.

PaiNWeeKeND™ ReGiONaL CONFeReNCe SeRieS

2020

pain management for the main street practitioner ● Scottsdale az

March 21–22 ● St. Louis mo April 18 ● Dallas t x May 2 ● Houston tx May 16

● Philadelphia pa

May 30 ● Atlanta ga June 6 ● San Diego ca June 13 ● Tampa fl June 27 *Additional dates / locations will be added throughout 2020.

visit www.painweekend.org for more information.

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Fiona Barwick PhD

Fiona Barwick is a Clinical Assistant Professor at Stanford University School of Medicine, and Director of the Sleep & Circadian Health Program at the Stanford Sleep Medicine Center in Redwood City, California. Dr. Barwick coauthored her article with Heather King phd, a Clinical Assistant Professor at Stanford Pain Management Center in Redwood City, California.

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Maria C. Foy PharmD, BCPS, CPE

Maria Foy is Pharmacy Care Coordinator in Palliative Care at Abington Jefferson Health in Pennsylvania. Maria has authored a chapter on pain management in Pharmacotherapeutics for Advanced Practice and has lectured nationally and locally on pain management, symptom management, chronic pain, and substance use disorder.

David M. Glick DC, DAIPM, CPE, fASPE

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David Glick has specialized in the evaluation of chronic and complex pain pathologies for over 30 years. He is a speaker focusing on education to improve differential diagnosis and clinical management of neuropathic and musculoskeletal pain syndromes. He has served on the Board of Directors for the American Society of Pain Educators and been faculty at PAINWeek since its inception. Dr. Glick was recognized for his dedication as the 2009 recipient of the Richard Weiner Pain Educator of the Year award

Courtney M. Kominek PharmD, BCPS, CPE

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Courtney Kominek is a Clinical Pharmacy Specialist—Pain Management at the Harry S. Truman Memorial Veterans’ Hospital in Columbia, Missouri. She coauthored her article with Abigail T. Brooks, pharmd, BCPS, who is a Clinical Pharmacy Specialist at the West Palm Beach VA Medical Center in Florida. Courtney and Abigail completed their PGY2 Pain Management and Palliative Care Pharmacy Residency together at the West Palm Beach VA Medical Center.

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Not only can you take our faculty home with youâ&#x20AC;&#x201D; now you can also bring them to the gym 365 days a year!

By Maria Foy PharmD, BCPS, CPE

Many challenges associated with the elderly can impact pain control.

Potential for treatment-related complications and adverse effects increase as we age, often due to metabolic changes…

By Maria C. Foy PharmD, BCPS, CPE

pain management in the older adult

geriatric

Abstract

Pain is a common medical issue in the aging population. Older adults are often at risk for severe pain, particularly pain related to cancer; the majority of deaths from cancer are in those >65 years of age. A study conducted by the National Institute of Health (NIH) demonstrated that >50% of respondents had issues with pain in the prior 30 days.1 Another study showed presence of pain in 45% to 85% of elderly adults, with frequency similar for men and women.2 Underreporting is common, especially in patients suffering from dementia or end-stage disease. Uncontrolled pain may deter participation in rehabilitation and activities of daily living and increase the risk of falls. Decreased socialization, insomnia, cognitive impairment, disability, and malnutrition can also occur. Healthcare utilization and costs have escalated due to pain management issues.3 Many challenges associated with the elderly can impact pain control. Potential for treatment-related complications and adverse effects increase as we age, often due to metabolic changes seen in the aging process. Pain can negatively affect sleep, appetite, strength, sexual function, and mobility. Difficulties in communicating the presence of pain may be related to hearing loss and cognitive impairment.

Physical, social, and psychological beliefs may impact willingness to utilize recommended treatment modalities, thereby limiting analgesic choices. For example, reluctance to use stronger analgesics due to fear of addiction or stigma may be seen especially in the current environment of the opioid crisis.

Anxiety, fear, and ability to concentrate may adversely affect relationships and socialization. Stoicism and feeling that pain is a punishment from God may originate from cultural and spiritual philosophies. Quality of life can be impacted if challenges cannot be overcome.

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Table 1. Sources of Pain in the Elderly Nerve pain (neuropathic pain) ▸ Diabetes ▸ Herpes zoster ▸ Nerve injury from surgery/amputations ▸ Cancer pain

Musculoskeletal/chronic pain ▸ Back pain ▸Joint

pain ▸ Arthritis Acute pain/postoperative pain Headache Leg cramps/restless legs

PK/PD As the body ages, pharmacokinetic and pharmacodynamic changes can affect how we react to medications. Consideration of these changes is needed to drive appropriate treatment choices. Since the elderly have more body fat and less body water than younger adults, higher levels of lipophilic medications and lower levels of hydrophilic medications may result in an increased risk of adverse effects.4 The average kidney function of an 80-year-old is generally 50% of a 20-year-old, therefore decreased elimination may lead to adverse events because of accumulation of renally excreted medications. Protein binding and liver metabolism may also be impacted, resulting in altered plasma levels of medications that may predispose the patient to harmful side effects. Motility of the gastrointestinal tract is slowed, possibly causing a build-up of blood levels of orally administered medication. Adjustment of doses and/or dosing frequency should be considered.

Pain Assessment Before appropriate treatment strategies can be recommended, a good assessment of the cause, type, and anticipated duration of pain should be determined.

Pain in the elderly can originate from sources that increase in prevalence as we age (Table 1). Determining the source and type of pain can help provide guidance on an appropriate initial treatment plan.

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Pain can be acute or chronic. Acute pain, often referred to as nociceptive pain, is generally short in duration, has a known etiology, and is proportional to the inciting factor. Objective signs, such as grimacing, increased blood pressure, and elevated heart rate are usually present. This type of pain is functional in nature, telling the person to stop whatever action is causing the discomfort. In acute pain, nerve endings, referred to as nociceptors, are responsible for facilitating transmission of the pain signal to the brain. For example, when you touch a hot stove, signals sent to the brain via nociceptors will then relay a message from the brain to the site of injury, telling you to remove your hand from the stove and protecting you from further tissue damage. Acute pain is usually described as sharp, aching, and throbbing.

Chronic pain persists beyond the usual healing time of an injury. Neuropathic pain, chronic in nature, no longer serves the purpose of protecting us from further injury. Some types of chronic neuropathic pain are associated with actual damage within the central nervous system, such as in multiple sclerosis, where nerve demyelination can be identified as the cause of pain. Neuropathic pain is often described as burning, tingling, stabbing, or electric shock-like, and will often radiate from one area to another. Chronic pain may be due to structural changes in the pain system itself, referred to as neuroplasticity.

The pain system becomes “sensitized” with nerve signals firing at a lower threshold and more often than normal. In some sensitized pain conditions, such as fibromyalgia, a source for the pain is often absent—no biological reason

In the elderly population, several principles for pain management should be considered. Improvement in function and quality of life should be the main goal of therapy.

for the pain can be foundâ&#x20AC;&#x201D;and pain is often facilitated by the presence of comorbid psychological factors, such as anxiety, depression, and catastrophizing behaviors. These patients need a more biopsychosocial approach to treatment, using psychological interventions aimed at acceptance and coping skills in addition to pharmacologic and nonpharmacologic strategies.

In order to identify and differentiate types of pain, a good pain assessment should be performed by using an appropriate tool based on the condition of the patient.4 In a patient able to self-report, the mnemonic P, Q, R, S, T, U can be used to help remember what should be queried in order to differentiate types of pain. Questions can be asked of the patient:

P = When did the pain present?

What precipitated the pain? What palliates the pain?

communicate. An example of an observational scale for this patient population is the PAINAD scale: Pain Assessment in Advanced Dementia.5 This scale can be used in patients who cannot verbalize information or answer questions related to what may be causing their discomfort. Points are given for behaviors that can represent pain, such as facial grimacing, inability to be consoled, rigid body language, groaning/crying, and labored breathing.

In addition to assessment tools, family members or caretakers may be able to report observations of pain-related behavior. Keep in mind that family will often overreport pain as they do not want to see their loved one suffering.

Conversely, physicians and nurses often underestimate pain, which may result in undertreatment.6

Treatment

Q = What is the quality (burning, achy, stabbing, tingling) of the pain?

In the elderly population, several principles for pain management should be considered. Improvement in function and quality of life should be the main goal of therapy. A balance of benefit vs burden of treatments should be taken into account when developing a treatment plan. Understanding benefits and risks of various methods of providing analgesia in the elderly will help determine the optimal choices for pain management.

Strategies to manage pain and disability include pharmacotherapy; interventional, complimentary, and physical therapy; and lifestyle changes.7 A multimodal approach to medication management will utilize different classes of medications in addition to nonpharmacologic treatments to synergistically provide relief, while minimizing potential adverse reactions when only one modality is used. When more than one medication is needed, start one medication at a time to determine its safety and efficacy. If an adverse reaction occurs when multiple agents are started together,

R = Where is region/location of the pain and does it radiate from one area to another?

S = What is the severity of the pain on a 0â&#x20AC;&#x201C;10-point scale?

T = What is the temporal pattern?

Is the pain present all the time or does it come and go?

U = How does the pain affect your

quality of life?

Multiple pain scales can to help determine pain severity, but most require the patient to be able to provide information to their healthcare provider. A unique problem is in those older patients who are unable to

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Table 2. Beers List: Examples of Pain and Symptom Management in the Elderly Analgesics ○ Nonselective NSAIDS ○ Meperidine ○ Opioids in patients with history of falls ○ Tramadol risk of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion

Psychotropics

Muscle Relaxants

○ Duloxetine in renal impairment, history of falls

○ Cyclobenzaprine ○ Carisoprodol

○ Tricyclic antidepressants

○ Methocarbamol

Anticonvulsants ○ Gabapentin/pregabalin in renal impairment, history of falls ○ Gabapentin/pregabalin in combination with opioids

○ Benzodiazepines

○ COX-2 inhibitors in heart failure or renal insufficiency

the medication causing the reaction cannot be determined, thereby eliminating medications that may be needed in the future. Dosing should be started low and titrated to response. Around-the-clock treatments for persistent pain may offer better pain relief compared to as-needed medications. For example, in our facility when an older patient is admitted for a fracture, around-the-clock acetaminophen is routinely initiated. Many of these patients receive adequate analgesia from the acetaminophen regimen, thereby minimizing the need for opioids.

Resources are available for information on medications to avoid in the elderly population. One example, the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, commonly called the Beers List, is a tool that can be used to provide guidance on medications to avoid or use with caution, in addition to medication and disease state interactions that may cause harm in the older adult (Table 2).8 In 2019, an updated Beers List was released by the American Geriatric Society.9 Examples of updates to the 2015 guidelines include 1) avoiding the use of opioids with benzodiazepines and gabapentinoids, 2) caution when using serotonin norepinephrine reuptake inhibitors (SNRIs) in patients prone to falls, and 3) risk of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion with tramadol.

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When determining the best treatment approach for analgesia in the elderly, choices are based on pain source, severity, and presence of medical comorbidities. Nonpharmacologic modalities, including physical, interventional, complimentary, and psychological approaches, are recommended for initial treatment either before using pharmacotherapy or in addition to medication management. Physical interventions include heating pads and/or cold packs, exercise, and massage. In patients able to participate, cognitive behavioral therapy, relaxation techniques, and meditation may be helpful.10 For more severe intractable pain, interventional procedures such as nerve blocks, spinal cord stimulators, intrathecal, and epidural injections may be considered (Table 3).

Pharmacologic options for treatment of pain include acetaminophen; nonsteroidal anti-inflammatory agents (NSAIDS); coanalgesics—medications with a primary indication other than analgesia—such as anticonvulsants and antidepressants; topical agents; and opioids.

When choosing an analgesic regimen, consider use of acetaminophen for mild to moderate pain, short-term use of NSAIDS for inflammatory pain, and low dose opioids if pain is persistent and severe. The temporal pattern of the pain should be assessed to determine if around-the-clock therapy is indicated. If pain is only occasional or associated

Table 3. Interventions for Elderly Patients Physical Interventions

Complimentary Approaches

Psychological Interventions Interventional

○ Heat pads

○ Relaxation

○ Cognitive therapy

○ Epidural injections

○ Cold packs

○ Imaging

○ Behavioral therapy

○ Nerve blocks

○ Massage

○ Distraction

○ Biofeedback

○ Kyphoplasty

○ Exercise

○ Meditation

○ Hypnosis

○ Spinal cord stimulators

○ Transcutaneous electrical nerve stimulation

○ Acupuncture

○ Intrathecal injections

with activity, as-needed treatment or pre-emptive analgesia may be adequate for pain control.

Acetaminophen is drug of choice when pain is mild to moderate in severity. Around-the-clock acetaminophen therapy may provide adequate pain relief for persistent pain because the older adult is more sensitive to pain medications. Acetaminophen has a good safety profile, with adverse events increasing with high dose and long-term use. Risk for overdose increases if acetaminophen-containing medications are unintentionally added to scheduled dosing. Using acetaminophen around-the-clock with low dose opioids as needed for breakthrough pain would be a good initial strategy when pain is severe. In addition, combining agents with different mechanisms of action may also improve pain control while minimizing side effects.

NSAIDs are not the best option for treatment of prolonged pain in the older adult. They are listed on the Beers List as potentially harmful due to possible negative effects on blood pressure, kidney function, and heart failure management. The elderly population is at an increased risk of bleeding, especially if also receiving low dose aspirin, selective serotonin reuptake inhibitors, or therapeutic anticoagulation. If NSAID treatment is needed, consider short-term therapy using a COX-2 inhibitor or the addition of a proton pump inhibitor to traditional therapy to help reduce the associated bleed risk. Patients with cardiovascular disease should avoid the use of NSAIDS. Coanalgesics have been shown to be efficacious for pain, especially neuropathic in origin. By working at different areas of the pain pathway, coanalgesic agents can help improve pain control by providing a synergistic

effect through different analgesic mechanisms. Whenever coanalgesic therapies are initiated, dosing should be started low and titrated to a therapeutic target with adjustments needed for presence of comorbidities, such as renal or liver impairment. Antidepressants, antiepileptic medications, and topical agents are classes of medications often used in the treatment of pain. Pregabalin and gabapentin are the most common antiepileptics used for pain control. Antidepressant medications, such as tricyclic antidepressants (TCA) and SNRIs have also been shown to be beneficial. TCAs are generally not recommended for use in the elderly due to the possibility of anticholinergic adverse reactions and increased risk of falls. Often, one medication can be used for different medical problems, minimizing issues with polypharmacy. For example, use of pregabalin, indicated for general anxiety disorder and used for neuropathic pain, can help if comorbid anxiety and pain are present.

Opioid therapy may be appropriate for severe pain in the elderly. In the 2009 American Geriatric Society guidelines, opioids are suggested in addition to acetaminophen when acetaminophen monotherapy does not provide adequate analgesia.11 When choosing an opioid dose, keep in mind that the elderly are more sensitive to medications; therefore, treatment should be started at a 30% to 50% lower initial dose compared to general adult dosing recommendations. Understanding the pharmacokinetics, equianalgesic dosing, and potential adverse effects of different opioids can help determine an appropriate agent and dose. If intolerable or unmanageable side effects occur, a lower dose or another agent should be considered.

Reassess opioid therapy frequently and adjust the regimen based on response, presence of adverse reactions, or

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Table 4. Opioids: What to Watch For Opioid Adverse Effects

Opioid Overdose Indicators

Constipation

Intoxicated behavior: confusion, slurred speech, stumbling

Nausea

Feeling dizzy or faint

Urinary retention

Feeling or acting very drowsy, groggy, or nodding off to sleep

Pruritis

Unusual snoring, gasping, or snorting during sleep

Respiratory depression

Difficulty waking up from sleep and becoming alert or staying awake

Central nervous system effects

Depressed breathing, difficult to arouse despite sternal rub

symptoms of overdose (Table 4). When switching opioids, consider reduction of the equivalent dose due to possible incomplete cross-tolerance.

In some states, cannabis is legal and endorsed for treatment of intractable pain and other symptoms seen in the elderly, such as nausea, insomnia, and muscle spasms. If cannabis is indicated, less frequent, lower initial doses should be recommended, especially if the person is cannabis naïve. The elderly are at an increased risk for worsening cognition, sedation, and intoxication. Presence or history of substance use and psychiatric comorbidities should be evaluated before suggesting cannabis use. Cannabis is contraindicated in a patient suffering from or with a history of psychosis and in patients with a history of heart disease.12

References 1. Nahin RL. Estimates of pain prevalence and severity in adults: United States, 2012. J Pain. 2015;16(8):769–780.

2. Prostran M, Vujović KS, Vučković S, et al. Pharmacotherapy of pain in the older population: the place of opioids. Front Aging Neurosci. 2016;8:144.

3. Van der Leeuw G, Ayers E, Leveill SG, et al. The effect of pain on major cognitive impairment in older adults. J of Pain. 2018;19(12):1435–1444.

4. Sera L, Uritsky T. Pharmacokinetic and pharmacodynamic changes in older adults and implications for palliative care. Prog Palliat Care. 2016;24(5): 255–261. Available at: www.tandfonline.com/doi/abs/10.1080/09699260.2016.1192319.

5. Zwakhalen S, Hamers JP, Abu-Saad HH, et.al. Pain in elderly people with severe dementia: a systematic review of behavioural pain assessment tools. BMC Geriatr.

2006;6:3.

6. Herr K, Coyne PJ, McCaffery M, et al. Pain assessment in the patient unable to self-report: position statement with clinical practice recommendations.

Pain Manage Nurs. 2011;12(4):230–250.

7. Johnson T. Chronic pain: a multidimensional disease. PMIR. 2012. Available at: painjuryrelief.com/chronic-pain-a-multidimensional-disease.

Conclusion Pain in the elderly is common and often underrecognized and undertreated. Safe prescribing with the goal of improving quality of life, balanced with related burdens of treatments, is needed to decrease residual harm. Pain etiology should be determined to tailor therapies based on best practice and evidence for efficacy.

Multimodal analgesia should be the focus of treatment by combining medications with different mechanisms of action, in addition to using nonpharmacologic interventions aimed at improving pain control. Lower initial doses and cautious initiation of each agent is needed to assess benefits and side effects. Potentially inappropriate medications should be avoided to minimize the risk of harm in the older adult.

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8. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. J Am Ger Soc. 2015;63(11):2227–2246.

9. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674–694.

10. Hartjes TM, Meece L, Horgas AL. Assessing and managing pain, agitation, and delirium in hospitalized older adults. Am J Nurs. 2016;116(10):38–46.

11. American Geriatric Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pain Med. 2009;10(6):1062–1083.

12. Van den Elsen GA, Ahmed AI, Lammers M, et al. Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Res Rev. 2014;14:56–64.

By David M. Glick DC, DAAPM, CPE, FASPE

regional pain syndromes

(LBP) seems as prevalent as the common cold. Even evolving technology has been unable to offer treatment for this apparently “simple” condition. LBP is still problematic for the patient and a costly burden to the healthcare system. The purpose of this discussion is to elucidate the rationale behind LBP’s treatment problem and offer clinical pearls to improve treatment. Given that most of the tools needed to reduce the clinical impact of LBP are available, the question is, “How do we apply them?”

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In a recent journal article reporting

incidence and prevalence of LBP, the authors identified the root of the treatment problem: There seems to be no agreement among researchers regarding the definition of LBP.1 It is essentially a regional complaint with one or more causes. In the case of headaches, clinicians seek to classify and characterize the subtype to determine the most appropriate treatment. Such clinical specificity is often missing, however, when discussing LBP. More importantly, the authors of that article concluded that multiple LBP definitions may lead to inappropriate LBP treatments. There have been numerous attempts to detail a road map for treatment. One of the more recent thorough discussions of LPB implies that there is a broad understanding of LBP, including pathophysiology, mechanisms, and pharmacological, nonpharmacological, and surgical options for treatment. The authors proposed an algorithm for clinical management of LBP that seems reasonable, emphasizing starting with the history and clinical examination and then attempting to map a course to identify causes and treatment selection.2 Clearly the goal was to mitigate the seemingly arbitrary treatments patients often receive in

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the real world. Yet, why has chronic LBP been cited as the second most frequent reason to visit a physician, the fifth most common cause for hospitalization, and the third most common cause for surgery?3-8 Confusing the matter further, nonspecific LBP, described as not having a well-defined cause, has been cited as representing 90% to 95% of all pain causes.9,10 One could arguably consider that classifying LBP as â&#x20AC;&#x153;without an underlying causeâ&#x20AC;? as contributing to failed outcomes: there must be a root cause.

The problem is the failure to identify the cause of an individual patientâ&#x20AC;&#x2122;s LBP. In determining treatment for a medical condition/disease, frequently the most common solution is contained in a guideline. The guidelines for treating LBP are numerous, and seem to differ in recommendations, seemingly influenced by the organization that promulgated them.11 Contrast LBP treatment with the treatment of chest pain. When a patient presents to an emergency department at any hospital with the complaint of chest pain, with potentially life-threatening sequelae, there is a concerted effort to identify the underlying cause to prevent mortality. Yet because LBP carries no such

Even when [remedies] are available, pain reduction reaches only 30% in about 50% of treated patients. …that would be analogous to having a car serviced and expecting a third of the problem to be addressed half the time.

Is there a consumer who would tolerate such poor car repair outcomes?

Are we holding healthcare for treatment of pain, such as LPB, to a lower standard than automobile repair?

urgency, treatments are often randomly attempted based on an institutional guideline or a provider’s clinical background.

Cosio has written that the sentiments of many healthcare providers mirrored those of the subjects in The Emperor’s New Clothes.12 He emphasized that causes for chronic pain, including LBP, are many, with complicated (and, for some patients, due to location or cost, difficult to attain) remedies. Even when they are available, pain reduction reaches only 30% in about 50% of treated patients. In real world terms, that would be analogous to having a car serviced and expecting a third of the problem to be addressed half the time. Is there a consumer who would tolerate such poor car repair outcomes? Are we holding healthcare for treatment of pain, such as LPB, to a lower standard than automobile repair?

Attempts to document the existence of comorbidities experienced by those with LBP has identified no less than 31 conditions/physical diseases including rheumatoid arthritis, osteoarthritis, and osteoporosis, and also cardiovascular and cerebrovascular problems. In fact, the authors recommended that physicians treating LBP extend their history and diagnostic analysis skills to embrace related comorbidities.13 Further complications arise when depression and anxiety disorders are considered: independent of LBP vs those attributed to LBP. The strongest conclusion from an extensive literature review of depression and pain comorbidity was that the combination of pain and depression was associated with far worse clinical outcomes.14

Researchers from Australia’s George

Institute for Global Health conducted a meta-analysis of 35 published clinical trials with >6,000 participants, and found that only 1 in 6 people taking NSAIDs for LPB experienced a meaningful reduction in symptoms.15 Therapies included over-the-counter and prescription strength NSAIDs; those who took NSAIDs were 2.5 times more likely to experience gastrointestinal problems. This data suggests that generally considered first-line interventions for LBP might be antithetical.

The NIH/National Institute of Neurological Disorders and Stroke published a Low Back Fact Sheet in 2014 that did not offer much confidence in any treatments.16 In general, medications suggested for LBP caused side effects, potentially led to serious adverse events, reacted to other medications, and had possibly unproven benefits.

Anticonvulsants were the exception; they may be useful in treating radicular pain. Unfortunately, while widely prescribed for LBP, in a recent meta-analysis, evidence pointed to anticonvulsants as ineffective for treatment of LBP lumbar radicular pain.17 More concerning was the finding of equally high quality evidence that gabapentin and pregabalin are associated with excess risk for adverse events. The same article noted that while epidural steroids may have short-term benefit in some conditions, outcomes were worse for those with spinal stenosis who received the injections. As for surgical options, the takeaway message was that not all procedures are helpful and there is little evidence to identify which procedures were effective for particular conditions.

30

Providers often rely on technology

to help determine the underlying cause of LBP. Arguably the greatest influence for care may be the findings of an MRI. This should be alarming, as pathologies attributed to musculoskeletal findings seen on imaging studies may not be clinically relevant. Not much has changed since Jensen and his group published a study in 1994 that reported that 52% of a group of asymptomatic subjects had at least a single disc pathology on an MRI of the back.18 A similar study by Jarvik and his group found that of 148 asymptomatic subjects evaluated, 69 (46%) had never experienced low back pain. There were 123 subjects (83%) with moderate to severe desiccation of ≥1 disc, 95 (64%) with ≥1 bulging disc, and 83 (56%) with loss of disc height. 48 subjects (32%) had ≥1 disc protrusion, and 9 (6%) had ≥1 disc extrusion.19 Clearly there is a high prevalence of degenerative pathologies in clinically asymptomatic patients.

Is anything different for acute LBP patients undergoing lumbar MRIs? Yu and his group retrospectively studied 3,107 lumbar spine MRIs taken at emergency departments over the course of a month in China for patients presenting with acute LBP. Only 41.3% of the MRIs showed findings of potential significance, although they were not necessarily clinically correlated, and 58.7% were completely normal.20 Consider a patient who underwent an epidural or even an oral steroid to address a suspect disc pathology and obtained clinical benefit from the treatment. Since most agree the disc pathology would likely still be present on imaging, the clinical result is a scenario where a pathology seen on imaging studies is

31

now asymptomatic, essentially validating the rationale to question the clinical significance of pathology seen on imaging studies.

More healthcare providers are begin-

ning to acknowledge the financial burden to patients and the healthcare system that can be attributed to over-relying on imaging studies without clinical correlation.21,22 There appears to be an identifiable emotional cost as well. In workers’ compensation cases, early use of MRI was associated with increased likelihood of disability and poorer clinical outcomes.23 There is a broad potential clinical burden when considering side effects and adverse events associated with treatments that may not be helpful.2,10,13,14 Technology alone does not yet provide all the answers.

In reviewing literature and clinical guidelines, there is a 2-part clinical conundrum relative to treating LBP: 1) how to establish a patient-centered differential diagnosis of the underlying pathology or pathologies, and 2) how to identify the most appropriate treatment for a particular patient. The most important components of patient engagement are the history and clinical examination. The title of a 2013 Indian Journal of Pain review

article, “The art of history taking in patient with pain: an ignored but very important component in making diagnosis,” addresses the issue.24 The article’s intent was to highlight that the fundamental tenet of patient assessment was being ignored. In the absence of an adequate clinical assessment and without a detailed thorough history, providers increase the risk for an inadequate diagnosis or a misdiagnosis. Such, in turn, would result in unnecessary tests and treatments, including surgeries. A proper history, supported by a physical examination and diagnosis of the exact nature and/or underlying cause of pain, is the most important and first building block to determining the most clinically appropriate treatment and addressing any pain pathology, including LBP. One of the most significant barriers to adequate treatment of LBP may be something as simple as time. Tsiga et al found that under time pressures, adherence to guidelines for history taking, clinical examination, and advice giving were adversely affected and resulted in less thorough examinations and abbreviated advice on lifestyle.25 It is possible to conceive of a model that could positively address time constraints while improving clinical outcomes and lowering healthcare costs. The savings realized from eliminating the need for treatments that are more likely to be less effective and eliminating the cost of potentially unnecessary tests and treatments could be used to offset the increased cost of a more thorough clinical assessment. The thousands of dollars potentially saved from a single surgery could offset the cost of at least 150 extended consultations. In 2006, the total US economic impact of LBP was estimated at more than $100 billion.26 More recent insurance company data from 2014 suggest the average cost related to a single back injury ranges from $40,000 to $80,000.27 Clearly there is room for improvement through reassignment of monies already being spent.

In the case of chronic LBP, the most

effective intervention may be the “reset switch.” By the time a patient has had multiple analgesic treatments, there is the potential to overmodulate the nervous system, theoretically helping to maintain pain. There is also the tendency to treat other symptoms or medication side effects.

We at PAINWeek say that “Education is the best analgesia.” Aside from the enhanced ability for patients to play a role in their own care, better awareness and recognition of intended treatment goals help prevent overtreatment and mitigate side effects as well as adverse events. If a patient is aware that a medication is expected

32

to offer a 30% to 50% improvement, a reasonable goal can be recognized. If they are expecting 100% relief, they may report the medication as not being effective, which can lead to an unnecessary increase in dosing, and thus a greater potential for side effects or adverse events. An anecdotal story: Through a recent telemedicine consult, a patient reported to me that, after years of chronic severe LBP, he experienced a 50% improvement after only having his underlying pathology identified and explained to him, along with a well-structured treatment plan.

The benefits of patient engagement strategies were well described by Cosio12 including the VA⁄DoD Stepped Care Plan model, for which the entire first step is “self-care.”28 It is reasonable that a patient who plays a greater role in her/his care is more likely to have a favorable outcome. For example, the morbidly obese patient who presents with a diet soda in one hand and cigarettes in the other, complaining that all treatments have failed, is far less likely to respond to further treatment than the patient who takes responsibility to improve his/her diet, exercise, and lifestyle.

Rule out red flags in evaluating a patient for LBP, especially when there is a change in clinical presentation. This author has seen patients referred for LBP treatments caused by dissecting abdominal aneurysms, deep vein thrombosis, and several variations of metastatic disease. The most common scenarios were an existing LBP pathology in which the patient experienced a change in clinical presentation, and/or new onset, with degenerative pathologies seen on imaging that proved to be clinically insignificant. Adequate history and clinical examination are essential; because patients often do not volunteer all relevant clinical information, taking an adequate history involves being a skilled interrogator.

There is no perfect universal clinical examination. It is best to develop a general examination sufficiently detailed to address most of the typical musculoskeletal pathologies that can contribute to, or manifest as, LBP. A group of core orthopedic and neurological tests can easily be incorporated into a routine examination and expanded when necessary, depending on examination findings. In the presence of a completely negative physical examination, there may be an underlying viscerosomatic referred pain; a physiologic cause, such as a vitamin, electrolyte, or hormonal problem; or even a medication side effect. This author has rarely observed a somatoform disorder, although secondary gain issues associated with a work-related injury are common. Maigne and Waldman both authored textbooks that can be helpful in building the core examination, as well as ancillary assessments when necessary.29,30 Know the anatomy of the back. If there is a single recommendation for evaluation of a patient presenting with back pain, it is visual and palpatory examination. Palpating structures that are painful is invaluable for localizing the pathology. It may be surprising to note

â&#x20AC;Śimaging studies should contribute to the overall clinical assessment but not solely guide treatment.

how often evidence of such an examination is absent from the medical record. Even something as simple as involuntary muscle spasms provide valuable information to demonstrate the veracity of patient complaints and differentially diagnose the basic problem. It is impressive how the presence of an underlying problem that manifests as an involuntary muscle spasm can be shown in a photograph, assisting with patient education, and potentially providing confirmation of a successful treatment.

Even with musculoskeletal back pain presentations, not all problems originate in the low back. It is common for hip and sacroiliac problems to manifest as left or right sided low back pain. Consider secondary piriformis entrapment caused by spasm or hyperactivity of piriformis muscle, compressing the peroneal division of the sciatic nerve; these patients often exhibit radiating pain that can mimic a lower lumber radiculopathy.31 In the case of a peroneal nerve anatomical anomaly where the peroneal or tibial branches pass through rather than under the piriformis, resulting in entrapment, patients are more difficult to treat than if they had a simple compression resulting from myofascial compression. Other variations to local proximal entrapments, such as the inferior gluteal nerve, exist as well.32 Many other peripheral entrapmentsâ&#x20AC;&#x201D;such as deep and superficial peroneal nerves, saphenous, sural, and more terminal branches of the tibial including medical and lateral plantar nervesâ&#x20AC;&#x201D; complicate diagnosis in the presence of radicular type lower extremity pain. Adding to the potential complexity of a clinical presentation, consider a variation of thoracolumbar junction syndrome where the underlying pathology is actually located between T10 and L2.29 Depending on the clinical variation, pain is often referred to the hip and SI joint and more often the low back resulting from spasm of the longissimus and quadratus lumborum muscles. Spasm of the quadratus lumborum can lead also to a secondary piriformis syndrome with entrapment of the peroneal nerve and present with radicular pain as well.

These patients often receive (numerous, failed) treatments

33

targeting the lower back, when the problem is actually above and below. A simple refocus of treatment to target the thoracolumbar can then yield an impressive clinical outcome.

Every patient is a case study of one. While most patients fit a pattern with respect to clinical manifestations of LBP, there are those who do not. Forcing a patient into a standardized plan that may not be appropriate can lead to failed treatment; a more patient-centered approach is needed.

Think outside the box. In the real world, it is not unusual to combine pharmacotherapies, such as an NSAID, antiepileptic, serotonin and norepinephrine reuptake inhibitor, or tricyclic antidepressant, and an opioid. While rational polypharmacy is a well-accepted practice, most published studies discuss each molecule independently, not necessarily in combination. Why not consider other nonpharmacologic interventions in the same way? If a patient happens to have an inflamed facet joint and radiculitis at the same level, it seems clinically intuitive to think about an intra-articular facet injection in combination with a transforaminal or interlaminar epidural injection. In a typical clinical scenario in which they are attempted individually, one aspect of the pathology still persists, essentially adversely affecting clinical outcomes. Theoretically, the lack of a favorable outcome can lead to a false impression ruling out an individual component of the pathology. Combining the injections, which differs from the usual clinical standard, trades the confirmation of a single local anesthetic block for an enhanced clinical outcome by addressing the broader complex pathology.

This author, in a multidisciplinary spirit, often combines interventional injections with manipulation or physical therapy, especially for facet mediated pain, mild radiculitis, or sacroiliac pathologies. In many cases, injections, manipulation, or therapy were attempted individually without success; yet, when combined, the clinical outcomes were dramatic. It is not uncommon to

assess a chronic LBP patient who has undergone multiple courses of individual treatment programs from differing specialties. When greater attention is paid to understanding the pathophysiologic components of the individual patient’s pathology, combining treatments from different disciplines may be effective in obtaining a favorable clinical outcome. An example is a medical branch block or an intra-articular facet injection with segment specific manipulation. Consider a clinical situation: multifidus and other muscle guarding may prevent an adequate response from segmental manipulation when performed individually. While the injection may provide temporary relief, since the biomechanical problem that led to the facet inflammation remains, the symptoms may return when the medication wears off. By using the treatments in conjunction, the injection allows for manipulation to be more effective and assist the healing process. Another example is a sacroiliac pathology, which may present as inflammation, restricted translational movement, or both.

In the case of both, an intra-articular injection helps to enable manipulation that alone would not be effective, and a local steroid assists healing, so the conditions are less likely to return once normal translation is restored.

Manipulation in conjunction with epidural injections may also be appropriate, although they should be considered with caution in the presence of a greater clinical risk.

Watch closely for clinical improvement. Often, when pain becomes chronic, peripheral and central sensitization set in. The resultant neuroplastic changes can be a considered a response to the body adapting to being in a state of pain. Now that we have taken a step backwards and reevaluated the patient, and considered a new patient-centered treatment, it is highly plausible that the underlying problem may be effectively addressed. While rarely discussed, neuroplastic changes can be reversed but will likely require time as the body adjusts to being in a normal state once again. When the patient returns after undergoing successful treatment, repeat examination often can demonstrate improvement or resolution of all the examination findings that led to the revised diagnosis and treatment, yet the patient may report the pain is unchanged. In this case, it is prudent to highlight such progress to the patient by reviewing the improved examination findings. Unfortunately, due to neuroplasticity, the patient’s perception of improvement often lags behind the actual clinical progress when they have experienced pain for some time. Best practices involve reassuring the patient, and considering the application of biopsychosocial strategies, in addition to continuing to wean them off medications that may longer be necessary.

Be aware of comorbidities and how such pathologies may present together. A patient with diabetic neuropathy can experience a back problem. That becomes complicated if a radicular pathology is superimposed over a diabetic neuropathy, and establishing a treatment goal is difficult. For example, a patient who experienced a

34

work-related back injury with radicular involvement came to see me. While we were able to successfully treat his back pain in short order, a clinical manifestation of peripheral vascular disease remained. Patients such as this one often refuse to acknowledge that some symptoms were not associated with their work-related injury. His peripheral vascular disease went untreated for some time, as symptoms in his legs and feet were attributed to the back injury.

Myofascial pain may have a neuropathic component but can also be associated with an electrolyte, vitamin, or hormonal deficiency, or a medication side effect, such as that involving statins. Clinical manifestation of myofascial pain may be minimal and not significantly impact the patient. Combine these issues with even a mild myofascial (or any other) pain, and the result tends to be cumulative and with more pronounced symptoms.

Dealing with multiple third-party payers for a patient with a work-related back injury who also shows evidence of hypomagnesemia adds many layers of complication.

Read the patient, not the imaging study. Many imaging studies are interpreted independent of detailed clinical information relative to the patient’s history and clinical examination findings. As previously stated, due to poor clinical correlation with and without pathologies seen on imaging studies, and the prevalence of pathologies on imaging studies on asymptomatic patients, imaging studies should contribute to the overall clinical assessment but not solely guide treatment. The chase for a pathology seen on an MRI, which may have gradually occurred over years in a patient who recently became symptomatic, should be a red flag for considering a different underlying cause of pain. Conversely, a normal study does not rule out back pathology. For example, in a patient with radiculitis, the inflamed nerve root will contribute to local muscle guarding or even spasm resulting in back pain, and likely radiation of symptoms as well. While the clinical manifestation of such a condition might be rather profound and very evident on examination, the MRI may appear completely normal.

We should not wait for a new test

or “miracle” treatment for low back pain. A multitude of treatments are available, in addition to the clinical ability to identify possible contributors to a patient’s pain. The secret lies in the ability to better triage the patient; that is, to better evaluate the patient and determine the most appropriate treatment(s) for a patient at a particular time, in a highly patient-centered manner. Complex problems may require complex solutions, and there is much to be

gained from a cooperative multidisciplinary approach.

The true answer to improved outcomes for treating LBP may simply be taking the time to apply existing knowledge and skillsets.

20. Yu L, Wang X, Lin X, et al. The use of lumbar spine magnetic resonance imaging in Eastern China: appropriateness and related factors. PLoS ONE. 2016;11(1):e0146369.

21. Deyo RA, Mirza SK, Turner JA, et al. Overtreating chronic back pain: time to back off? J Am Board Fam Med. 2009;22:62–68.

22. Flynn TW, Smith B, Chou R. Appropriate use of diagnostic imaging in low back pain: a reminder that unnecessary imaging may do as much harm as good.

J Orthop Sports Phys Ther. 2011;41:838–846.

References 1. Fatoye F, Gebrye T, Odeyemi, I. Real-world incidence and prevalence of low back pain using routinely collected data. Rheumatol Int. 2019;39:619–626.

23. Graves JM, Fulton-Kehoe D, Jarvik JG, et al. Early imaging for acute low back pain: one-year health and disability outcomes among Washington State workers.

Spine. 2012;37(18):1617–1627.

2. Chawla J, Berman S. Low back pain and sciatica. Medscape. Available at: emedicine.medscape.com/article/1144130-overview#a1.

24. Gurumoorthi R, Das G, Gupta M, et al. The art of history taking in patient with pain: an ignored but very important component in making diagnosis. Indian J Pain.

2013;27:59–66.

3. Anderssen GBJ. The epidemiology of spinal disorders. In: Frymoyer JW, ed.

The Adult Spine: Principles and Practice. New York: Raven Press; 1997:93–141.

4. Cunningham LS, Kelsey JL. Epidemiology of musculoskeletal impairments and associated disability. Am J Public Health. 1984;74(6):574–579.

25. Tsiga E, Panagopoulou E, Sevdalis N, et al. The influence of time pressure on adherence to guidelines in primary care: an experimental study. BMJ Open.

2013;3:e002700.

5. National Center for Health Statistics. Limitations of activity due to chronic conditions, United States, 1974. DHEW Publication No. (HRA) 77–1537.

1977;series10:No.111. Available at: www.cdc.gov/nchs/data/series/sr_10/sr10_111.pdf.

26. Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences [review]. J Bone Joint Surg Am. 2006;88(suppl 2):21–22.

6. National Center for Health Statistics. Surgical operations in short stay hospitals by diagnosis, United States, 1978. DHEW Publication No. (PHS) 82–1722.

1982;series13:no61. Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_061.pdf.

27. Ohio State University. Spine Research Institute. Addressing the high corporate costs of back pain (and other MSDs). August 15, 2014. Available at: spine.osu.edu/ blog/2014/08/addressing-high-corporate-costs-back-pain-and-other-msds.

7. National Center for Health Statistics. Inpatient utilization of short stay hospitals by diagnosis, United States—1973. DHEW Publication No. (HRA) 77–1776.

1976;series13:No.25. Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_025.pdf.

28. U.S. Department of Health and Human Services. National Pain Strategy.

Washington, DC: US Department of Health and Human Services; 2016. Available at: iprcc.nih.gov/sites/default/files/HHSNational_Pain_Strategy_508C.pdf.

8. National Center for Health Statistics. Surgical operations in short-stay hospitals: United States, 1978. DHEW Publication No. (PHS) 82–1722. 1982;series13:No.24.

Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_061.pdf.

29. Maigne R, Nieves WL. Diagnosis and Treatment of Pain of Vertebral Origin. 2nd ed.

Boca Raton, FL: CRC Press, Taylor & Francis Group; 2006.

30. Waldman SD. Physical Diagnosis of Pain: An Atlas of Signs and Symptoms. 3rd ed.

Philadelphia, PA: Elsevier; 2016.

9. Bardin LD, King P, Maher CG. Diagnostic triage for low back pain: a practical approach for primary care. Med J Aust. 2017;206(6):268–273.

31. Gujar B, Flores R. Entrapment neuropathies and compartment syndromes. In: Hochberg MC, Silman AJ, Smolen JS, et al, eds. Rheumatology. 6th ed. 2015:671–682.

10. Manchikanti L, Singh V, Datta S, et al. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician. 2009;12(4):E35–70.

32. Trescot AM. Inferior gluteal nerve entrapment. In: Trescot AM, ed.

Peripheral Nerve Entrapments. Switzerland: Springer; 2016:581-587.

11. Oliveira CB, Maher CG, Pinto RZ, et al. Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview.

Eur Spine J. 2018;27:2791–2803.

12. Cosio D. The emperor’s new clothes: multimodal engagement & improving access to care. PWJ. 2019;7(3):20–23.

13. Schneider S, Mohnen SM, Schiltenwolf M, et al. Comorbidity of low back pain: representative outcomes of a national health study in the Federal Republic of Germany. Eur J Pain. 2007;11:387–397.

14. Bair MJ, Robinson RL, Katon W, et al. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163:2433–2443.

15. Machado GC, Maher CG, Ferreira PH, et al. Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis. Ann Rheum Dis. 2017;76:1269–1278.

16. NINDS. NIH Publication No. 15–5161. Low back pain fact sheet. December 2014.

Available at: www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/ Low-Back-Pain-Fact-Sheet.

17. Enke O, New HA, New CH, et al. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ. 2018;190(26):E786-E793.

18. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med. 1994;331(2):69–73.

19. Jarvik JJ, Hollingworth W, Heagerty P, et al. The Longitudinal Assessment of Imaging and Disability of the Back (LAIDBack) Study: baseline data.

Spine (Phila Pa 1976). 2001;26(10):1158–1166.

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By Courtney M. Kominek PharmD, BCPS, CPE / Abigail T. Brooks PharmD, BCPS

As ph rm Cists, we et sked ll kinds of questions bout medic tions, nd ren l nd hep tic dysfunction dose djustments re some of the most common concerns.

In this 2-p rt rticle, we ex mine why cert in drugs require dose djustments in p tients with ren l dysfunction.

pharmacotherapy

Pain in chronic kidney disease

Patients with chronic kidney disease (CKD) have a high prevalence (58%) of pain.1 In end-stage renal disease (ESRD), pain can result from multiple causes related to hemodialysis (HD), such as muscular cramps, headaches, needling for HD, erythropoietin injections, or nondialysis, such as musculoskeletal or peripheral neuropathy.2,3 Musculoskeletal pain is the most common complaint.4

Pharmacokinetic considerations in CKD

Multiple physiological changes occur in CKD and can alter the pharmacokinetic characteristics of medications. Absorption is altered in CKD with increased gastric pH, which can lead to lower maximum plasma concentrations and changes the time to reach maximal concentrations. With CKD, decreased albumin levels and increased alpha-a-acid glycoprotein change the concentration of bound and free drugs. Fluid retention can increase total body water and change the volume of distribution of hydrophilic medications. Elimination of medication is influenced as well. There is a reduction in functioning nephrons, renal blood flow, glomerular filtration, and tubular secretion leading to accumulation of fluid.5 Similarly, there are considerations regarding medication removal from dialysis. Medications that have larger molecular weights are less likely to be removed by the dialysis filter. Highly protein bound medications are not removed due to the size of proteins. A large volume of distribution indicates that the medication enters the

38

tissues, so the medication is not accessible and cannot be removed. A medicationâ&#x20AC;&#x2122;s water solubility increases the likelihood that the agent will be removed by dialysis.

Highly water-soluble medications are more likely to be removed compared to highly lipophilic medications.6

Adapted WHO analgesic ladder

Many of us are familiar with the World Health Organization (WHO) analgesic ladder. The traditional ladder progresses along 3 steps from mild to moderate to severe pain. Nonopioids are used to manage mild pain (Step 1), weak mu-opioid agonists are used for moderate pain (Step 2), and strong mu-opioid agonists are used for severe pain (Step 3), with use of adjuvants throughout. (Donâ&#x20AC;&#x2122;t forget nonpharmacological approaches!) This ladder7 has been adapted to include medications safe for patients with CKD:

Step 1: Acetaminophen Step 2: Hydrocodone, tramadol Step 3: Buprenorphine, fentanyl,

hydromorphone, methadone

(Oxycodone is not addressed in some guidance7 while different resources place it in Step 28 or Step 3.4)

The Coalition for Supportive Care of Kidney Patients published guidance on appropriate medications

Table 1. Pain Medication Recommendations in CKD and ESRD2,8 Recommended

Use with Caution

Avoid

▸ Acetaminophen ▸ Buprenorphine ▸ Fentanyl ▸ Gabapentin/Pregabalin ▸ Hydromorphone* ▸ Methadone

▸ Hydrocodone ▸ Oxycodone ▸ Tramadol

▸ Codeine ▸ Meperidine ▸ Morphine ▸ Nonsteroidal antiinflammatory drugs

*Exceptions: Stage 4 or 5 CKD and if dialysis is interrupted/stopped

to treat pain in patients with CKD. This guidance includes the adapted WHO analgesic ladder as well as a table reviewing medications recommended (green), medications to use with caution (yellow), and medications to avoid (red) (Table 1).8

Acetaminophen

Acetaminophen is the preferred first-line medication for mild pain in patients with CKD according to the adapted WHO analgesic ladder.2,7,9 The terminal half-life of acetaminophen is extended in patients with renal dysfunction.7 Recommended adjustments in patients with creatinine clearance (CrCl) of 10–50 mL/min includes altering the dosing interval to every 6 hours. For CrCl < 10 mL/min or with dialysis, the dosing interval should be changed to every 8 hours.1 Even though HD removes about 66% of the drug, no supplemental doses are needed most likely due to the fact that acetaminophen is already dosed multiple times per day.1,2 Maximum daily dosing recommendations remain 4000 mg/day.1 Renal toxicity may occur in an acetaminophen overdose and is relatively uncommon, occurring in roughly 1% to 2% of patients. Little information is available related to the mechanism of renal toxicity in acetaminophen overdose, although several mechanisms are theorized. Glutathione depletion, which is thought to be a risk factor, appears to reflect an acute tubular necrosis process. n-acetylcysteine administration has shown benefit in reducing acetaminophen-induced hepatoxicity.10 (As we will discuss in part 2 of this article, similar results for nephrotoxicity have not been shown.)

Nonsteroidal antiinflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are problematic in patients with reduced kidney function because they inhibit prostaglandin synthesis and negatively affect renal blood flow and glomerular filtration. This can lead to acute renal failure. Elderly patients or those suffering from dehydration, bleeding, heart failure, hypertension, or cirrhosis are at increased risk for developing renal adverse effects. In addition, NSAIDs can contribute to sodium and potassium retention, acute interstitial nephritis, and analgesic nephropathy. Typically, renal effects are reversible but they can lead to chronic renal failure with long-term use.7 The Kidney Disease Outcomes Quality Initiative guidelines for CKD recommend avoiding NSAIDs in patients with a glomerular filtration rate (GFR) < 30 mL/ min/1.73 m2. Long-term use of NSAIDs in patients with GFR < 60 mL/min/1.73m2 should be avoided and, if NSAIDs are used short-term in this population, consider dose reduction. NSAIDs should be avoided concomitantly with lithium.11 If they are used, short-acting NSAIDs are preferred over long-acting to reduce the duration of hemodynamic interaction. Sulindac or salsalate may be preferred to NSAIDs due to lower hemodynamic issues because of less prostaglandin inhibition, and prostaglandin production remains conserved. Topical products are preferred over oral NSAIDs because of lower systemic bioavailability that reduces risk for systemic adverse effects. NSAIDs combined with other medications including renin-angiotensin system inhibitors can be even more problematic due to potential synergistic decline in GFR.4

39

Table 2. SNRI Considerations in Renal Dysfunction13-15 SNRI Medication

Renal Considerations

Duloxetine

Avoid GFR < 30 mL/min

Milnacipran

▸ No adjustment in mild renal dysfunction ▸ CrCl 5–29 mL/min maintenance dose reduced by 50% (50 mg/day) May increase to 100 mg/day ▸ Avoid ESRD

Venlafaxine ER

▸ With GFR 10–70 ml/min, reduce dose 25%-50% ▸ In HD, reduce total daily dose by 50%

Antidepressants

There are several considerations related to antidepressant use in patients with renal dysfunction (Table 2). Although tricyclic antidepressants (TCAs) do not have recommended renal dose adjustments, patients with renal dysfunction may be more susceptible to typical TCA adverse effects. Use of TCAs should follow the “start low and go slow” approach.12 Often TCAs are precluded from use because of other nonrenal comorbidities such as glaucoma, benign prostatic hypertrophy, or constipation. Serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used in the management of chronic pain. Duloxetine should be avoided with GFR < 30 mL/ min due to increased plasma concentrations, especially of the metabolites.13 Venlafaxine also requires renal dose adjustments. With GFR 10–70 ml/min the dose should be lowered by 25% to 50% and in HD the dose should be reduced 50%.14 Milnacipran does not require adjustments with mild renal dysfunction, but with crcl 5–29 mL/min the maintenance dose should be reduced 50% with titration to maximum 100 mg/day. Additionally, milnacipran should be avoided in ESRD.15

Anticonvulsants

Many of the anticonvulsants used to treat chronic pain require renal dose adjustments (Table 3).

There are numerous gabapentinoid products with specific dose adjustments, but typically dose reductions begin with CrCl < 60 mL/min. In addition to reducing the dose of gabapentinoids, there are recommendations to adjust the dosing frequency. Recommendations vary regarding

HD and gabapentinoids, from avoiding use altogether to needing supplemental doses.16-19 The effect of carbamazepine in persons with renal dysfunction is not known.20 Lamotrigine should be used with caution in persons with renal dysfunction; limited data are available, but about 20% of the drug is removed by HD. Reduced maintenance doses of lamotrigine may be effective.21 Beginning with CrCl < 80 mL/min, dose adjustments of levetiracetam are needed. About 50% of levetiracetam is removed by HD, necessitating supplemental doses.22 When using oxcarbazepine with CrCl < 30 mL/min, half of the typical initial dose should be used in 2 divided doses with weekly titrations in increments of 300–450 mg/day.23 Topiramate needs dose adjustment of 50% reduction at initiation with CrCl < 70 mL/min, and supplemental doses are needed after HD.24

Skeletal muscle relaxants

Chlorzoxazone, cyclobenzaprine, and orphenadrine do not require renal dose adjustments.25-27 The kidney excretes baclofen 70% to 80% as unchanged drug, so renal dose adjustments are needed beginning with CrCl < 80 mL/min with additional reductions needed with commensurate renal decline. Intrathecal baclofen should be avoided in renal impairment. Skeletal muscle relaxants (SMRs) other than baclofen should be considered in HD since baclofen is likely removed.28 Specific dose adjustments are not provided for carisoprodol other than adjusting to clinical response and degree of renal dysfunction.

Additionally, carisoprodol is removed by both HD and peritoneal dialysis.29 Diazepam is excreted in the urine;

40

Table 3. Anticonvulsants and Renal Considerations16-24,37 Medication

Renal Considerations

Carbamazepine

Unknown

Gabapentin, gabapentin enacarbil, gabapentin CR

▸ Renal dose adjustments needed beginning at CrCl < 60 mL/min See individual prescribing information for each formulation ▸ Supplemental doses needed after HD or dose standard dose after completion of HD

Lamotrigine

▸ Use with caution ▸ Limited data available ▸ Reduced maintenance doses may be effective ▸ 20% eliminated by HD

Levetiracetam

▸ CrCl > 80 mL/min, 500–1500 mg q12h ▸ CrCl 50–80 mL/min, 500–1000 q12h ▸ CrCl 30–50 mL/min, 250–750 mg/day q12h ▸ CrCl < 30 mL/min, 250–500 q12h ▸ 50% removed during HD ▸ 500–1000 mg q24h ▸ Supplemental doses after HD (250–500 mg)

Oxcarbazepine

▸ CrCl < 30 mL/min ▸ Start at ½ the usual dose (300 mg/day in 2 divided doses) ▸ Titrate in weekly increments of 300–450 mg/day ▸ Use IR vs XR formulation in HD

Pregabalin, pregabalin CR

▸ Renal dose adjustments needed beginning at CrCl < 60 mL/min ▸ Supplemental doses needed after HD or dose standard dose after completion of HD ▸ Avoid pregabalin CR with HD

Topiramate

▸ CrCl < 70 mL/min: initiate at 50% usual dose ▸ Supplemental doses needed in HD

no specific renal dose adjustments are provided but the drug should be adjusted based on response and degree of impairment.30 Metaxalone should be used in caution in patients with renal dysfunction and is contraindicated in those with severe renal impairment.31 For methocarbamol, caution should be used in patients with severe renal impairment or in HD.32 The clearance of tizanidine is reduced about 50% in renal dysfunction. Dose reductions are recommended for tizanidine at CrCl < 25 mL/min. If larger doses are required, increasing the dose is recommended rather than dosing more frequently.33 Table 4 reviews SMRs.

41

Opioids

Several opioids, including codeine, meperidine, and morphine should be avoided in patients with renal dysfunction. Codeine is 90% renally cleared. With reduced renal excretion, metabolites can accumulate leading to respiratory depression. Meperidine is contraindicated in patients with CKD due to the accumulation of neurotoxic metabolites. Similarly, morphine should be avoided in those with CrCl < 30 mL/min because of the buildup of neurotoxic metabolites.4 Although not nephrotoxic, tramadol is renally cleared and requires renal dose adjustments. Accumulation

Table 4. Skeletal Muscle Relaxants and Renal Considerations25-33 Medication

Renal Considerations

Baclofen

▸ Kidney excretes 70%-80% as unchanged drug ▸ CrCl > 90 mL/min, no adjustment needed ▸ CrCl 50–80 mL/min, reduce PO dose by 1/3rd ▸ CrCl 30–50 mL/min, reduce PO dose by 1/2 ▸ CrCl < 30 mL/min and NOT on dialysis: reduce PO dose by 2/3rd ▸ HD: consider other medications due to adverse effects, likely removed by HD ▸ Use intrathecal baclofen with caution in renal impairment

Carisoprodol *AVOID IN GENERAL

▸ Adjust based on clinical response and degree of impairment ▸ Specific recommendations not provided ▸ Removed by HD ▸ Removed by peritoneal dialysis

Chlorzoxazone

No dosage adjustment needed

Cyclobenzaprine

No dosage adjustment needed

Diazepam

▸ Excreted via urine ▸ Monitor and adjust dose based on response and level of impairment ▸ No specific dosage adjustments provided

Orphenadrine

No dosage adjustment needed

Metaxalone

▸ Use with caution ▸ Contraindicated in significant renal impairment

Methocarbamol

Caution is needed with severe renal impairment or HD

Tizanidine

▸ CrCl < 25 mL/min, reduce individual doses ▸ If higher doses needed, increase dose as opposed to dosing more frequently ▸ Clearance reduced about 50% in renal impairment

of the parent drug and metabolites can occur with advanced CKD (CrCl < 30 mL/min). A dose of 100 mg PO BID is recommended in advanced CKD and 50 mg PO BID in HD. In uremia, patients on tramadol may be at higher risk for seizures and respiratory depression.1,4,34,35 Buprenorphine is safe choice for patients with advanced CKD. It is hepatically metabolized to norbuprenorphine, which has weak mu opioid receptor activity.

About 30% of the parent and metabolite are cleared renally.

It is likely not removed by dialysis. No dose adjustments are needed.4,6,35 Fentanyl, another reasonable option in CKD, is metabolized by CYP3A4 to inactive metabolites. It is not

42

dialyzed, although 75% is eliminated in the urine. One issue that has been reported is binding of fentanyl to dialysis filters.4,6,35 Methadone can be an option in CKD patients, although it should be administered by experienced pain specialists. The primary route of metabolism and elimination is hepatic. About 20% of methadone is eliminated through the kidneys and there is biliary-fecal compensation in ESRD. No dose adjustments are needed in CKD. Overall, the pharmacokinetics in CKD is comparable to healthy patients. Methadone is not routinely removed via dialysis.4,6,36 Hydrocodone is metabolized in the liver to

Renal impairment and how to dose adjust medications can be a clinically complex and daunting process.

In addition, it is clear that certain pain medications should be avoided all together in patients with renal impairment.

several metabolites. It undergoes renal excretion, and about 25% is excreted in active metabolites in the urine.7 This suggests the potential for accumulation of parent drug and active metabolites.1 Dosage adjustments are likely needed but no specific recommendations are provided.7 It is placed in the “use with caution” category given the limited information about its use. However, the evidence that is available suggests limited adverse effects with use.8 Hydromorphone requires renal dose adjustments and is removed during HD. Hydromorphone undergoes phase II metabolism to hydromorphone-3-glucuronide, which can accumulate and lead to neurotoxicity. Reducing the dose of hydromorphone by 50% in moderate renal insufficiency is recommended since the exposure to a 4 mg dose is doubled with CrCl 40–60 mL/min. For severe renal impairment, the hydromorphone dose should be lessened by 75% since the systemic exposure to a 5 mg dose is tripled with CrCl < 30 mL/min. About 50% of hydromorphone is removed during dialysis.1,4,6,35 Oxycodone is metabolized by CYP3a4 to noroxycodone (active) and CYP2d6 to oxymorphone (active).

Both concentrations of the parent drug and metabolites are increased in renal failure. There is limited data on the effect of dialysis on oxycodone, but available information suggests that it is likely removed via dialysis. If used in CKD, doses adjustments are needed with close monitoring.4,6,35

43

Conclusion

Renal impairment and how to dose adjust medications can be a clinically complex and daunting process. In addition, it is clear that certain pain medications should be avoided all together in patients with renal impairment.

The views and opinions expressed in this presentation are those of the authors and do not necessarily reflect the official policy or position of any agency of the United States government, including the Department of Veterans Affairs, as well as employers, employee affiliates and/or pharmaceutical companies mentioned or specific drugs discussed.

References 1. Koncicki HM, Unruh M, Schell JO. Pain management in CKD: a guide for nephrology providers. Am J Kid Dis. 2017;69(3):451–460.

2. Raina R, Krishnappa V, Gupta M. Management of pain in end-stage renal disease patients: short review. Hemodial Int. 2018;22(3):290–296.

3. Davison SN. Chronic pain in end-stage renal disease. Adv Chronic Kidney Dis. 2005;12(3):326–334.

4. Pham PC, Khaing K, Sievers TM, et al. 2017 update on pain management in patients with chronic kidney disease. Clin Kidney J. 2017;10(5):688–697.

5. Mathew RO, Bettinger JJ, Wegrzyn EL, et al. Pharmacotherapeutic considerations for chronic pain in chronic kidney and end-stage renal disease. J Pain Res. 2016;9:1191–1195.

21. Lamotrigine package insert. Baltimore, MD: Lupin Pharmaceuticals, Inc; October 2018.

22. Levetiracetam package insert. Lawrenceville, GA: Exelan Pharmaceuticals, Inc; December 2018.

6. Atkinson T, Fudin J, Wegrzyn EL, et al. Dialysis, opioid, and pain management: where’s the evidence? Pract Pain Manage. 2014;14(8):49–57.

23. Oxcarbazepine package insert. Hawthorne, NY: Taro Pharmaceuticals USA, Inc; August 2014.

7. Launay-Vacher V, Karie S, Fau JB, et al. Treatment of pain in patients with renal insufficiency: the World Health Organization three-step ladder adapted.

J Pain. 2005;6(3):137–148.

24. Topiramate package insert. Baltimore, MD: Lupin Pharmaceuticals Inc; July 2018.

8. Treating pain in advanced CKD and dialysis patients: clinical algorithm and preferred medications. 2016. Available at: cpb-usw2.wpmucdn.com/blogs.nursing. gwu.edu/dist/a/4/files/2019/05/TreatingPaininLateCKD11–2016.pdf or https://bit.ly/2QlxYAn.

25. Chlorzoxazone package insert. Parsippany, NJ: Actavis Pharma, Inc: March 2015.

26. Cyclobenzaprine package insert. Birmingham, AL: Oxford Pharmaceutical, LLC; January 2018.

9. Barakzoy AS, Moss AH. Efficacy of the world health organization analgesic ladder to treat pain in end-stage renal disease. J Am Soc Nephrol. 2006;17(11):3198–3203.

27. Orphenadrine package insert. Baltimore, MD: Lupin Pharmaceuticals, Inc; February 2019.

10. Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol. 2008;4(1):2–6.

28. Baclofen package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc; October 2015.

11. Inker LA, Astor BC, Fox CH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713–735.

29. Carisoprodol package insert. Kansas City, MO: Nostrum Laboratories, Inc; April 2019.

30. Diazepam package insert. Morgantown, WV: Mylan Pharmaceuticals Inc; May 2018.

12. Eyler RF, Unruh ML, Quinn DK, et al. Psychotherapeutic agents in end-stage renal disease. Semin Dial. 2015;28(4):417–426.

31. Metaxalone package insert. Parsippany, NJ: Actavis Pharma, Inc; June 2017.

13. Cymbalta package insert. Indianapolis, IN: Lilly USA, LLC: October 2019.

32. Methocarbamol package insert. Piscataway, NJ: Camber Pharmaceuticals, Inc; March 2013.

14. Effexor XR package insert. Philadelphia, PA: Wyeth Pharmaceuticals LLC; December 2018.

33. Tizanidine package insert. Orlando, FL: Ingenus Pharmaceuticals, LLC; March 2019.

15. Savella package insert. Irvine, CA: Allergan USA, Inc; December 2018.

16. Neurontin package insert. New York, NY: Pfizer; February 2018.

34. Kafkia T, Chamney M, Drinkwater A, et al. Pain in chronic kidney disease: prevalence, cause and management. J Renal Care. 2011;37(2):114–122.

17. Lyrica package insert. New York, NY: Pfizer; June 2019.

35. Coluzzi F. Assessing and treating chronic pain in patients with end-stage renal disease. Drugs. 2018;78(14):1459–1479.

18. Gralise package insert. Neward, CA: Depomed, Inc; September 2015.

19. Horizant package insert. Atlanta, GA: Arbor Pharmaceuticals, LLC; October 2016.

36. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage.

2004;28(5):497–504.

20. Carbamazepine package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc; October 2018.

37. Lyrica CR package insert. New York, NY: Pfizer; October 2017.

Part 2 about hepatic dysfunction will appear in the next PWJ.

44

CHANGES WHAT HAPPENS HERE

EXCESS NGF IS ONE OF THE KEY DRIVERS OF CHRONIC PAIN In response to injury or inflammation, cells at the site of pain release a number of biochemical mediators, including prostaglandins, cytokines, and a neurotrophin called nerve growth factor (NGF). NGF plays a key role in driving chronic pain. Excess NGF can change the way nerves signal pain.

In the periphery, excess NGF can lead to peripheral and central sensitization, amplifying pain signaling and heightening the perception of pain.1-5

WHAT EXCESS NGF DOES HERE

Discover more at

KeyPainDrivers.com References: 1. Chang D, Hsu E, Hottinger D, Cohen SP. Anti-nerve growth factor in pain management: current evidence. J Pain Res. 2016;9:373383. 2. Pinho-Ribeiro F, Verri Jr W, Chiu I. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. 2017;38: 5-19. 3. Latremoliere A, Woolf C. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895-926.

4. McGreevy K, Bottros MM, Raja SN. Preventing chronic pain following acute pain: risk factors, preventive strategies, and their efficacy.

Eur J Pain. 2011;5(suppl):365-372. 5. Mantyh PW, Koltzenburg M, Mendell LM, Tive L, Shelton DL. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology. 2011;115:189-204.

PP-N1N-USA-0013-01 Š 2018 Pfizer Inc. All rights reserved. July 2018

By Fiona Barwick phd / Heather King phd

By Fiona Barwick phd / Heather King phd

behavioral

and insomnia are major health problems that commonly co-occur. They are reciprocally related, but prospective research conducted over the past 15 years shows that disrupted sleep has a greater impact on subsequent pain than pain does on sleep. These findings suggest that treating insomnia to prevent and ameliorate chronic pain may be a promising intervention.

Cognitive behavioral therapy (CBT) is a widely used, empirically supported, and cost-effective therapy for insomnia and chronic pain and an important component in the biopsychosocial approach for treating any chronic condition. Efforts to use CBT to improve insomnia primarily and chronic pain secondarily, or to combine CBT protocols to improve insomnia and chronic pain simultaneously, have successfully improved sleep but not pain outcomes. Developing integrated CBT protocols that target and measure relevant outcomes over longer follow-up periods, especially for chronic pain, may yield better results.

48

At least 50% of individuals with insomnia suffer from chronic pain, and up to 88% of those with chronic pain report disturbed sleep…

Epidemic of Chronic Pain and Insomnia

Chronic pain—defined as persistent pain that lasts beyond the normal healing time—is an epidemic in the United States. One in 4 people currently experiences chronic pain, which can include back pain, migraines, and arthritis.1 Insomnia is also common in the general population, with as many as one-third or more of Americans reporting problems such as falling asleep, staying asleep, or waking up early and unable to return to sleep, and 10% or more meeting criteria for insomnia disorder.2,3 These conditions are independently linked to other medical and psychiatric comorbidities as well as increased rates of disability and reduced quality of life.4,5

The Reciprocal Relationship

Not surprisingly, these conditions commonly co-occur. At least 50% of individuals with insomnia suffer from chronic pain, and up to 88% of those with chronic pain report disturbed sleep, making it one of the most prevalent complaints among those who suffer from chronic pain.6-8 Broadly speaking, the relationship between these conditions is bidirectional, with people who report disturbed sleep experiencing more pain, and people who report higher levels of pain experiencing worse sleep. Pain can disrupt sleep, leading to microarousals and fragmented sleep, which in turn worsens sleep quality and reduces sleep quantity. Conversely, disturbed sleep can lead to greater pain sensitivity and reduced ability to tolerate or regulate pain, even after a single night. This creates a vicious cycle, wherein pain leads to poor sleep, which leads to worse pain in a downward spiral.5,9-14

target in efforts to prevent and ameliorate chronic pain.

The possibility of additional interventions is especially important for conditions like chronic pain, as research shows chronic conditions are inadequately treated using the biomedical model, which emphasizes medications, procedures, and surgeries. Instead, chronic pain conditions are best treated from a biopsychosocial perspective, which highlights the importance of addressing psychological, behavioral, and social factors that contribute to the individual experience of pain.18

CBT for Chronic Pain and Insomnia

CBT is a well-established and cost-effective treatment that employs a collaborative approach to target and change unhelpful beliefs and behaviors, whether about pain or sleep. During this treatment, individuals learn new coping skills for managing chronic conditions, skills that confer cumulative benefits and lead to increased self-efficacy. CBT is the most widely studied evidence-based treatment for addressing the psychosocial factors that contribute to chronic pain.19 It is also the recommended approach for treating insomnia because it is so effective—70% to 80% of individuals who complete treatment report significant reduction or total resolution of insomnia symptoms—and, as a result, is endorsed by several major health organizations, including the National Institutes of Health, American College of Physicians, British Psychopharmacological Society, and European Sleep Research Society.20-25 Its empirical effectiveness, as well as the reciprocal relationship between insomnia and chronic pain, make CBT for insomnia a potentially impactful intervention for preventing or ameliorating chronic pain.26,27

Combining CBT Protocols

Greater Impact of Disrupted Sleep on Chronic Pain

Interestingly, more recent and rigorously designed studies, including those that track sleep and relevant pain outcomes over a single week or many years, suggest that disrupted sleep may have a greater impact on chronic pain than pain does on sleep. Several prospective population-based studies that followed individuals for up to a decade or more showed that impaired sleep quality and quantity were associated with a 2- to 3-fold increase in risk of developing a new-onset pain condition or aggravating a current pain condition in subsequent years. However, individuals with chronic pain but no sleep problems at outset were <2 times as likely to develop chronic pain several years later.15-17 These findings suggest that treating insomnia may hold significant promise as an intervention

49

Initial research focused on using CBT protocols to treat insomnia with the expectation that better sleep would lead to less chronic pain. Although these studies consistently found that insomnia improved from pretreatment to posttreatment—including reductions in sleep onset latency and wakefulness at night, as well as improvements in sleep quality and total sleep time—they yielded no significant improvements in pain measures.28-32 Researchers attributed this lack of improvement to a failure to target chronic pain explicitly, so subsequent groups combined CBT protocols to target insomnia and chronic pain simultaneously. These studies employed widely different designs and, consequently, yielded very different results. The smallest study, which used a wait-list control and was randomized but not blinded, found no significant differences between treatment and control groups, which may have reflected a lack

…treating insomnia may hold significant promise as an intervention target in efforts to prevent and ameliorate chronic pain. …research shows chronic conditions are inadequately treated using the biomedical model… of power or the ability to find an existing effect.33 The largest study, a randomized controlled trial that compared groups receiving CBT for pain and insomnia, CBT for pain only, and an education control group, showed significant improvements on sleep measures and a nonsignificant trend toward improvements on pain measures in the CBT for pain and insomnia group compared to the other 2 groups.34 The midsized study, which was randomized but not blinded, showed significant improvements and large effect sizes from pretreatment to posttreatment on both sleep and pain measures in a combined CBT for pain and insomnia group compared to a symptom-monitoring control group.35

Design Challenges for Integrating CBT Protocols

The variability in treatment outcomes described above likely reflects differences in study design, suggesting that careful attention to these factors is critical.

First, developing protocols that target relevant outcomes and using instruments to measure those outcomes appropriately is essential. For example, evidence shows that unhelpful thinking about pain (eg, catastrophizing) and unhelpful behaviors around pain (eg, avoidance) are more likely to change than pain severity ratings. The significant improvements in both insomnia and chronic pain for the treatment vs control groups in the study conducted by Tang and colleagues may be ascribed to their inclusion of sessions that focused on reducing pain catastrophizing and pain avoidance as well as their use of instruments that measured these constructs.35 Second, understanding that CBT benefits are gradual and cumulative, especially for chronic pain, highlights the possibility that reductions in chronic pain resulting from improved sleep might take longer to manifest.

For example, Vitiello and colleagues completed their initial study in 2013, which found significant improvement in insomnia symptoms but no significant improvement on pain measures for a combined CBT for pain and insomnia group compared to a CBT for pain group and an education control group.34 However, when the authors conducted secondary analyses of their data comparing “sleep responders” (those who showed a ≥30% improvement on an insomnia measure from baseline to 2 months posttreatment) to “sleep nonresponders” (those who showed little to no change on the same measure), they found that sleep responders reported significant and sustained improvements in pain severity, pain symptoms and fear avoidance at 9- and 18-month follow-up periods compared to nonresponders.36 Similarly, a study conducted by Koffel and colleagues in 2016 showed that a decrease in sleep complaints at 3 months significantly predicted fewer pain symptoms at 12 months.17

50

Potential Promise of Integrated CBT Protocols

Chronic pain is a widespread, debilitating and costly condition that requires a biopsychosocial approach, including CBT, for effective treatment. Given its pervasiveness and intractability, any additional approaches that can prevent the onset or worsening of chronic pain, or can successfully augment the treatment of chronic pain, are to be sought out. Treating insomnia might offer such an approach. Insomnia commonly co-occurs with chronic pain, it has a potentially greater impact on pain than vice versa, and it can be treated successfully with many of the same CBT techniques used for chronic pain. Efforts to treat insomnia and improve chronic pain sequentially, or to create integrated protocols and target both conditions simultaneously, have met with limited success to date. Addressing those factors that most affect outcomes, including appropriate measures and adequate follow-up periods, may lead to more efficient and effective modalities for treating chronic pain and insomnia.

Conclusion

At Stanford, we are currently combining our efforts and expertise to develop and refine an integrated protocol for targeting the “pain insomnia phenotype.”37,38 In this protocol, CBT techniques for chronic pain and insomnia are integrated and sequenced within and across group sessions to optimize learning and implementation of skills for improving both conditions simultaneously.

This 6-week group, which meets for 2.5 hours weekly and is co-led by a pain psychologist (HK) and sleep psychologist (FB), includes patients with comorbid chronic pain and insomnia. It focuses on improving quality of sleep, increasing engagement in activities that are limited by pain, and teaching self-management strategies that confer gradual and cumulative benefits. We have included an outline of our group treatment protocol along with a case example to highlight the impact our A.S.A.P. (“All About Sleep and Pain”) protocol has had on Ms. H’s life. After completing the A.S.A.P. group, Ms. H showed a significant decrease in reported insomnia symptoms and unhelpful beliefs about sleep, a modest improvement in sleep hygiene, and small improvements in pain catastrophizing and pain-related beliefs about sleep. Although our protocol is in the early stages of development, preliminary data suggest it is a promising treatment option for comorbid pain and insomnia.

A.S.A.P. All About Sleep and Pain: Group Treatment Protocol Session 1 ▸Neuroscience

of chronic pain and insomnia: Education on how the brain is affected by the experience of chronic pain and insomnia and how CBT can positively impact neuroplasticity ▸Behavioral

activation: “Motion is lotion for the joints” ▸Self-regulation:

Diaphragmatic breathing and wind-down period before bedtime ▸Goal

Setting and Action Plan Session 2 ▸Action

Plan check-in ▸Time-based

pacing for chronic pain: Using time to change the “boom and bust” cycle by balancing activities that increase pain with activities that do not increase pain ▸Normal

sleep architecture: Education on normal adult sleep patterns including individual variability, and how these patterns change across the lifespan ▸Self-regulation:

Progressive muscle relaxation and wake-up routine ▸Updated

Action Plan Session 3 ▸Action

Plan check-in ▸Review

of time-based pacing for chronic pain ▸Science

of sleep-wake: Role of sleep drive and circadian rhythms in regulating sleep-wake cycles ▸Bed

compression and regular sleep schedule: Limiting time in bed, re-associating bed with sleep, and creating a consistent sleep/wake schedule ▸Self-regulation:

Guided visualization ▸Updated

Action Plan Session 4 ▸Action

Plan check-in ▸Review

of time-based pacing and bed restriction ▸Unhelpful

thinking styles: Education on unhelpful thoughts regarding pain and sleep ▸Catch

it, Check it, Change it: Cognitive restructuring technique ▸Self-regulation:

Body scan ▸Updated

Action Plan Session 5 ▸Action

Plan check-in ▸Review

of time-based pacing and bed restriction ▸Basics

of mindfulness: Education on the purpose and philosophy of mindfulness ▸Self-regulation:

Mindfulness meditation ▸Updated

Action Plan Session 6 ▸Action

Plan check-in ▸Review

of coping skills for chronic pain and insomnia ▸Resources

for self-management of chronic pain and insomnia ▸Relapse

prevention plan

51

A.S.A.P. Case Example:

Past Treatments

Treating comorbid chronic pain and insomnia

Pain: Trigger point injections, occupational therapy, physical therapy, bursa/joint steroid injection, TENS

Identifying Information: Ms. H is a 65 y/o single female with fibromyalgia, rheumatoid arthritis, neuropathic pain, generalized anxiety and insomnia. She has had chronic pain for >30 years, and chronic insomnia >25 years.

Sleep: No treatment for insomnia or other sleep problems

Medications: Xanax (alprazolam), Enbrel

Personalized A.S.A.P. Goals 1) increased walking tolerance 2) improved sleep quality 3) less anxiety Activity

Pretreatment

Posttreatment

Time-based walking

10 minutes

30 minutes

Self-regulation

None

30-minute wind down before bedtime, diaphragmatic breathing “throughout the day”

Time in bed

9 hours

6 hours

Sleep onset

1.5 hours

<30 minutes

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13. Ødegård S, Sand T, Engstrøm M, et al. The impact of headache and chronic musculoskeletal complaints on the risk of insomnia: longitudinal data from the Nord-Trøndelag health study. J Headache Pain. 2013;14(1):24.

6. Smith M, Perlis M, Smith M, et al. Sleep quality and presleep arousal in chronic pain. J Behav Med. 2000;23(1):1–13.

14. Tang N, McBeth J, Jordan K, et al. Impact of musculoskeletal pain on insomnia onset: a prospective cohort study. Rheumatology (Oxford). 2015;54(2):248–256.

7. Tang N, Wright K, Salkovskis P. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. J Sleep Res. 2007;16(1):85–95.

15. Afolalu EF, Ramlee F, Tang NK. Effects of sleep changes on pain-related health outcomes in the general population: a systematic review of longitudinal studies with exploratory meta-analysis. Sleep Med Rev. 2018;39:82–97.

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16. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013;14(12):1539–1552.

28. Currie SR, Wilson KG, Pontefract AJ, et al. Cognitive-behavioral treatment of insomnia secondary to chronic pain. J Consult Clin Psychol. 2000;68(3):407–416.

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2016;35(1):41.

29. Edinger JD, Wohlgemuth WK, Krystal AD, et al. Behavioral insomnia therapy for fibromyalgia patients: a randomized clinical trial. Arch Intern Med. 2005;165(21):2527–2535.

18. Gatchel RJ, Peng YB, Peters ML, et al. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581–624.

30. Jungquist CR, O’Brien C, Matteson-Rusby S, et al. (). The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain.

Sleep Medicine. 2010;11(3):302–309.

19. Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev. 2012;11:CD007407.

31. Rybarczyk B, Stepanski E, Fogg L, et al. A placebo-controlled test of cognitive-behavioral therapy for comorbid insomnia in older adults. J Consult Clin Psychol.

2005;73(6):1164.

20. Buscemi N, Vandermeer B, Friesen C, et al. National Institutes of Health State of the Science Conference Statement: manifestations and management of chronic insomnia in adults: summary. Sleep. 2005;28(9):1049–1057.

32. Vitiello MV, Rybarczyk B, Von Korff M, et al. Cognitive behavioral therapy for insomnia improves sleep and decreases pain in older adults with co-morbid insomnia and osteoarthritis. J Clin Sleep Med. 2009;5(4):355.

21. Morin CM, Bootzin RR, Buysse DJ, et al. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998–2004). Sleep. 2006;29(11):1398–1414.

33. Pigeon WR, Moynihan J, Matteson-Rusby S, et al. Comparative effectiveness of CBT interventions for co-morbid chronic pain & insomnia: a pilot study. Behav Res Ther.

2012;50(11): 685–689.

22. Qaseem A, Kansagara D, Forciea M, et al, for the Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians.

Ann Intern Med. 2016;165(2):125–133.

34. Vitiello MV, McCurry SM, Shortreed SM, et al. Cognitive‐behavioral treatment for comorbid insomnia and osteoarthritis pain in primary care: the lifestyles randomized controlled trial. J Am Geriatr Soc. 2013;61(6):947–956.

23. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700.

35. Tang NK, Goodchild CE, Salkovskis PM. Hybrid cognitive-behaviour therapy for individuals with insomnia and chronic pain: a pilot randomised controlled trial.

Behav Res Ther. 2012;50(12):814–821.

24. Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487–504.

36. Vitiello MV, McCurry SM, Shortreed SM, et al. Short-term improvement in insomnia symptoms predicts long-term improvements in sleep, pain, and fatigue in older adults with comorbid osteoarthritis and insomnia. Pain. 2014;155(8):1547–1554.

25. Wilson SJ, Nutt D, Alford C, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol. 2010;24(11):1577–1601.

37. Smith MT, Edwards RR, McCann UD, et al. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep. 2007;30(4):494–505.

26. Finan PH, Buenaver LF, Coryell VT, et al. (2014). Cognitive-behavioral therapy for comorbid insomnia and chronic pain. Sleep Med Clin. 2014;9(2):261–274.

38. Sutton BC, Opp MR. Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration. Sleep. 2014;37(3):505–513.

27. McCrae CS, Williams J, Roditi D, et al. Cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) in adults with comorbid chronic insomnia and fibromyalgia: clinical outcomes from the SPIN randomized controlled trial.

Sleep. 2019;42(3).

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By Kevin Zacharoff MD, FACIP, FACPE, FAAP

By Kevin Zacharoff MD, FACIP, FACPE, FAAP

the basics of pain treatment P2

By Kevin L. Zacharoff MD, FACIP, FACPE, FAAP

The International Association for the Study of Pain (IASP)1 proposed an update to its definition of pain in 2019 to “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”While it might be surprising to consider that the definition of pain would need to be updated, it is worth remembering that pain is a ubiquitous and highly personal phenomenon. As clinicians know, the same set of circumstances may cause significant pain in one patient and little or none in another. The challenge then is not only to identify the type and source of pain a patient is experiencing, but also to assess the severity and impact of the painful condition in order to ensure optimal treatment.

In many ways, pain is somewhat of a “black box,” in that only the sufferer truly understands the experience that is pain. Pain has both subjective and objective components and, while the proportions may be variable, all must be assessed with at least the intent to treat. Additionally, consideration must be given to the temporal nature of the pain, as treatment strategies for acute pain may differ dramatically from those for chronic pain.

Incidence and prevalence of pain

Almost everyone has experienced pain at some time in their life; most of us on numerous occasions. In fact, pain is one of the most common reasons that people seek medical attention in the US each year. Of further significance is that >50% of patients look to their primary care providers for assessment, diagnosis, and treatment. On average, 15% to 20% of Americans experience chronic pain each year; other sources report between 26.3 and 100 million people.2-5 It is worth noting that these estimates do not include the significant number of people who experience acute pain each year. Regardless of the exact number, chronic pain affects the lives of millions of Americans annually. Adult Americans seek medical attention on average 3.1 times per year,6 and the majority of these contacts are precipitated by complaints of some type of pain. Pain is often associated with wide ranges of injury and disease, and in some situations is the disease itself. Some conditions may have pain and associated symptoms arising from a discrete cause, such as iatrogenic postoperative pain, or pain associated with pressure related to a tumor. There are also conditions

in which pain constitutes the primary problem, such as neuropathic or headache pain. The reality is that when we try to quantify how often pain occurs, it can be hard to estimate, as the incidence and prevalence of the associated conditions vary as well.

Furthermore, research shows that the incidence of chronic pain may vary based on a number of different demographic factors such as age, race, and gender.7-10 Additionally, many factors have been deemed responsible for disparities in pain assessment, and ultimately treatment in these differing populations as well. A variety of factors for disparate treatment have been identified, including clinician variability, cultural or gender-based differences, and even clinical setting (such as emergency department vs clinic).

The dynamics of chronic pain among diverse populations, including factors such as employment status, cognition, healthcare accessibility, healthcare utilization patterns, and pain coping across various groups are not well understood.11 This variability can make the quantification of incidence and prevalence difficult.

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Surgery is the single largest cause of acute pain in the Patient descriptions of pain United States, with approximately 46 million inpatient Pain is often described by patients experiencing it in words surgical procedures performed each year.12 The major- that relate to physical sensations, such as “tingling” or ity of patients in the US report moderate to severe pain “aching,” and in emotional words, such as “horrifying” or “terpost-surgically, even in the face of current treatments and rifying.” To illustrate pain, people often use vivid verbal analogies such as “I feel like someone is stabbing me repeatedly techniques. and twisting the knife” or “My head feels like it’s in a vise being Additionally, as the American population continues to age, squeezed tighter and tighter.” Behavioral responses, includthere is an increase in the burden of arthritis pain and ing grimacing, bracing, or rubbing the affected area, result chronic joint symptoms in people aged ≥65.13 In a 1999 poll, in nonverbal communication about pain. These behaviors, a large proportion of respondents indicated some degree along with the accompanying physiologic signs and sympof disability secondary to pain, with 2 of 3 elderly individ- toms of autonomic activation (eg, tachycardia, tachypnea), uals responding that pain kept them from participating in are common in acute pain but are uncommon in chronic pain, activities. Arthritis is the leading cause of disability, with even when it is severe. Physicians and other healthcare proapproximately 39 million medical visits and 500,000 hos- viders may feel challenged when called on to evaluate and pitalizations per year.14 Cancer, the second leading cause treat painful sensations and the suffering they evoke. of death in America,15 is associated with chronic pain in approximately 67% of patients.16

Conclusion

Burden of pain on society

The 2011 Institute of Medicine Report3 estimated the annual economic costs associated with chronic pain to be between $560 and $635 billion annually in direct medical assessment, treatment, and lost productivity. The loss of productivity is often largely invisible to employers, because it includes underperformance on the job (presenteeism) due to pain, as well as time off the job (absenteeism).16 Chronic back pain is one of the major causes of absence from work in people <45 years of age.17 The American Productivity Audit, a survey of 28,902 working adults, found the following in relation to pain-related impact on work productivity18: ○ 52.7% of the work force surveyed reported having headache, back pain, arthritis, or other musculoskeletal pain in the prior 2 weeks ○ 12.7% of the work force lost productive time in a 2-week period due to pain ○ Headache (5.4%) was the most common pain condition prompting lost productive time, followed by back pain (3.2%), arthritis pain (2%), and other musculoskeletal pain (2%) ○ Headache produced, on average, 3.5 hours of lost productive time per week ○ Overall, workers lost an average of 4.6 hours per week of productive time due to a pain condition ○ Lost productive time from common painful conditions was estimated to cost $61.2 billion per year ○ 76.6% of lost productive time was explained by reduced work performance (presenteeism), not absenteeism

Much has been done to recognize the importance of alleviating the adverse consequences of pain and improving pain treatment. The United States government officially designated 2000 to 2010 as the Decade of Pain Control and Research. In 2000, pain also earned the official designation as “the fifth vital sign,” and patients were (and currently are) encouraged to understand that they have the right to effective assessment and adequate treatment of pain.15 Despite the high prevalence and incidence of pain, healthcare provider education and training is disproportionately low compared to that for other medical conditions, especially for those frontline practitioners who are often called upon to assess and treat it. In the face of today’s “opioid epidemic,” assessing and adequately treating the common complaint of pain has become even more challenging not only for clinicians but also for patients in need.

References 1. The International Association for the Study of Pain. IASP Terminology.

Available at: www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698.

2. Bonnie RJ, Morgan AF, Phillips JK. Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse. Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. The National Academies Press. July 2017.

3. The Institute of Medicine. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Washington, DC: The National Academies Press. 2011.

4. Dahlhamer J, Lucas J, Zelaya, C, et al. Prevalence of Chronic Pain and HighImpact Chronic Pain Among Adults — United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67:1001–1006.

5. Interagency Pain Research Coordinating Committee. National pain strategy: a comprehensive population health-level strategy for pain. Washington, DC: US Department of Health and Human Services, National Institutes of Health. 2016.

6. Green CA, Anderson KO, Baker TA, et al. The unequal burden of pain: confronting racial and ethnic disparities in pain. Pain Med. 2003;(4):277–294.

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7. Ortega RA, Youdelman BA, Havel RC. Ethnic variability in the treatment of pain.

Am J Anesthesiol. 1999;26(9):429–432.

13. Centers for Disease Control and Prevention (CDC). Public health and aging: projected prevalence of self-reported arthritis or chronic joint symptoms among persons aged >65 years—United States, 2005–2030. MMWR Morb Mortal Wkly Rep. 2003;52:489–491.

8. Mossey JM. Defining racial and ethnic disparities in pain management.

Clin Orthop Relat Res. 2011;469(7):1859–1870.

14. National Center for Health Statistics. Health, United States, 2009: With Special Feature on Medical Technology. Hyattsville, MD. 2010.

9. Hoffman KM, Trawalter S, Axt JR, et al. Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites. Proc Natl Acad Sci U S A. 2016;113(16):4296–4301.

15. Fitzgibbon DR. Cancer pain: management. In: Loeser JD, Butler SH, Chapman CR, et al, eds. Bonica’s Management of Pain. 3rd ed. Philadelphia, PA: Lippincot, Williams & Wilkins; 2001:659–703.

10. National Center for Health Statistics. Health, United States, 2006 With Chartbook on Trends in the Health of Americans. Hyattsville, MD: 2006:68–71.

16. National Institutes of Health. NIH Guide: New Directions in Pain Research I. September 4, 1998.

11. DeFrances CJ, Lucas CA, Buie VC, et al. National Hospital Discharge Survey.

National health statistics reports; no 5. Hyattsville, MD: National Center for Health Statistics. 2008.

17. Andersson GB. Epidemiological features of chronic low-back pain. Lancet.

1999;14(9178):581–585.

12. Centers for Disease Control and Prevention (CDC). Prevalence of disabilities and associated health conditions among adults—United States. MMWR Morb Mortal Wkly Rep. 2001;50:120–125.

18. Stewart WF, Ricci JA, Chee E, et al. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003;190:2443-2454.

ur next article in this series will address the pathophysiology of pain.

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Peter Pryzbylkowski md Interventional Pain Physician Relievus

GPS Cherry Hill, nj Typical Day Chronic pain consults and follow ups in the office. I’m in the OR typically two days a week performing minimally invasive interventional pain procedures. Persona I do feel ready to be a next generation opinion leader

in the pain space. I have been very fortunate to know and be friends with well-respected leaders in the field. Their guidance and collaboration on projects have spurred me on to bigger and better things. Social Media It’s amazing to see the social media presence of so many of my colleagues and the companies I consult for. I’m constantly checking Facebook and Instagram to see what they are up to. Contribution My most meaningful contribution to patient care is following the evidence. I pride myself on being an evidence based physician first. If there are no data to support the use of a new technique or intervention I won’t employ it in my practice. I also think that treating the patient and not the disease has allowed me to rapidly expand my patient population. People The public figure I most admire is Eddie Vedder of Pearl Jam. I’ve been to many of his concerts and the emotion he puts into every performance is amazing. He’s also an excellent surfer, which I admire. Words The book that has most influenced me is When Breath Becomes Air by Paul Kalanithi. It’s the story of a neurosurgeon who is diagnosed with terminal lung cancer. In essence the physician becomes the patient. It opened my eyes to never take anything for granted and to seize each and every day. Popcorn Growing up in a Philadelphia suburb I’m a sucker for any Rocky movie. The idea that hard work pays off no matter what the odds is carried through in all those films. PAINWeek PAINWeek gives me the opportunity to help educate a different medical community. I’m accustomed to speaking on panels in my field of expertise to other pain specialists. What draws me to pw is the ability to educate general practitioners and advanced practice providers on what is changing in the interventional pain space.

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By Charles E. Argoff

md, cpe

The practitioner’s first step always is actually listening to the patient, taking what they say seriously, and addressing what they’re hearing in a logical manner.

However, it’s also important to consider whether or not there are other possible explanations for the patient’s complaint of pain.

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In an August 2019 study,

In 1 of the 1st large studies to focus on mental health effects associated with hip pain, researchers analyzed data from

a team investigated the polarization properties of coronary atherosclerotic plaques in

patients with coronary artery disease.

12 catheterizations were performed on patients affected by acute coronary syndrome, and 18 on patients with symptoms of stable angina pectoris. The 30 catheterizations provided images for each procedure, including 342 cross-sectional plaque images and 244 images from the fibrous caps of the atherosclerotic lesions responsible for high risk or stable symptoms.1

Inhaled cannabis reduces

self-reported headache & migraine severity by 47.3% and 49.6%, repectively. Information was submitted by

tablets are taken worldwide yearly.

For nearly 50 years, synthetic salicylic acid (sa) was used to treat pain, fever, and inflammation before the advent of aspirin.

After 3 decades of work beginning in 1990, a team identified ~2,000 human proteins that bind to the SA derivative 4azsa.

The pool was narrowed to 95 candidate SA-binding proteins (cSABPs), falling into 5 categories. 2 proteins, ENO1 and PKM2, topped the list. Researchers found that genes encoding the 95 csABPs were implicated in >1,100 diseases across 22 physiological categories.3

hip

surgery patients, ages 29 to 41, gathered in 12 smaller studies conducted since 2014. The results suggest it may be advisable to start screening young patients with hip pain for depression and anxiety, especially before they undergo procedures.5

American Cancer Society projects

Residents of states where cannabis has

been legalized are more likely to believe it has beneficial effects, including health benefits in treatment of pain and anxiety or depression.

Researchers surveyed a nationally representative sample of

patients who used an app

new cases of multiple myeloma in the US in 2019. A phase II trial of immunotherapy involved 58 centers/8 countries.

times to track headache changes from before to after cannabis use, and another 653 who used the app US adults for their beliefs and opinions

times to track migraine severity changes.

Men reported reduction > women (90.0% vs 89.1%).2

regarding cannabis. Most respondents believed that cannabis is beneficial for pain management: 73% in recreationally legal states, 67% in medically legal states, and 63% in nonlegal states.4

In the low dose (LD) group, 31% of patients (30 out of 97) achieved lowered cancer amounts; 60% (18 pts) had ≥very good partial response.

Higher dose (HD): 34% (34 out of 99) achieved an overall response, with 59% (20 patients) achieving ≥very good partial response. Follow up = 6.3 months (LD), 6.9 months (HD). Median progression-free survival = 2.9/4.9 months. 8% (8 out of 97 LD) and 10% (10 out of 99 HD) stopped treatment due to side effects: nausea (24% LD, 32% HD), fatigue (16%, 26%), blurred vision (22%, 30%), and dry eye (14%, 23%).6

1. pain.sh/7ey 2. pain.sh/fip 3. pain.sh/c2974 4. pain.sh/mdb 5. pain.sh/52f 6. pain.sh/u2l

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2

Migraine Treatment and Troubles

Charles E. Argoff MD, CPE

What a person experiences during a migraine, loosely speaking, is a very sensitized brain. Migraine facts: ● Migraine is among the most disabling disorders in the world ● Migraine is the most common type of primary headache ● 30 to 40 million Americans experience migraine Of those diagnosed, many have headaches so frequently they should be on preventative treatment. Either they’re not recognized as having headaches frequently enough or the preventative medicines are ineffective or poorly tolerated. Much of the treatment armamentarium comes with significant unwanted effects. Among the side effects of current FDA approved preventative medicines for migraine:

1

Pain in the Elderly: What to Consider

Tanya J. Uritsky PharmD, BCPS; Maria C. Foy pharmD, BCPS, CPE

Findings from an NIH funded study looking at the impact on pain in the older adult found that >50% of people surveyed had pain within the last month, often in ≥1 location.

● Liver toxicity ● Weight gain ● Hair loss ● Tremor ● Glaucoma ● Kidney stones ● Cognitive impairment ● Blood pressure changes

Why? ● People gain weight as they age ● Their bones break down ● They have spinal cord issues Drugs for the elderly: care must be taken—

3

● Older organs don’t function as they once did ● Even if labs show that the kidneys or liver are working well, the organ is not working like that of a 20-year-old ● Dose adjustments may be needed more frequently ● Fat has changed in the body ● A drug is going to move through the body differently ● Older people are much more sensitive to dosing of many opioids or analgesics

Sleep: A n Important Ingredient in the Healing Process Martin Cheatle PhD

Individuals who suffer from chronic pain often present with significant medical/psychiatric comorbidities that can exacerbate pain and contribute to disability and a further erosion of quality of life. One way to improve patient’s quality of life? Improve their sleep. ● 70% to 80% of patients with chronic pain have sleep disturbance ● Pain and sleep are bidirectional: not getting restorative rem sleep causes release of interleukin 6, a proinflammatory cytokine, causing inflammation in the body. If it is generated by the inflammatory process, like in rheumatoid or osteoarthritis, pain will be worse with bad sleep ● When sleep deprived, pain tolerance is lowered: If a cold pressor test (putting an arm in a bucket of cold water) is performed, a pain patient can keep it there, let’s say, 30 seconds; that’s the pain tolerance. If you rem-deprive sleep and retest, they’ll last maybe 15 seconds ● With sleep deprivation comes a higher level of irritability ● A baseline depression + sleep deprivation = a greater level of depression

Important pointers: ● Just start lower—you can always go up, but once you start too high, you get a lot of side effects that could affect that patient. So, start low, go slow, but go… ● Longer dosing intervals are recommended ● Monitor monitor monitor! ● Don’t forget acetaminophen: it is a very mild pain killer but works for elderly populations because they’re sensitive to it. We’ve put patients on acetaminophen around the clock and they barely use any opioid medications ● nsaids or ibuprofen drugs: you may think they’re very mild but they can be harmful to the elderly.

And they’re on the Beers List of medications that can be harmful to older people

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4

5

Leigh Ann Wilson LCSW; Collin V. Montgomery APRN

Stephen J. Ziegler PhD, JD

The WHOs of Sickle Cell Disease

Hemp in Pain Management: Are We Lost in the Weeds?

The United States is struggling with how to deal with undertreatment of pain and abuse of opioids. At the same time, millions of people in third-world countries are dying without access to any opioids, due in large part to a variety of barriers relating to distance, regulation, and knowledge. Could marijuana be the solution to these problems? Although marijuana continues to remain prohibited by federal law and treaty, several countries and US states have defied these prohibitions by passing their own laws and regulating marijuana for recreational or medical purposes.

Who? The CDC estimates 100,000 people in the US are living with sickle cell disease ● Both mother and father have to have sickle cell disease to pass it along ● There’s a 25% chance that a child will have sickle cell disease—that is 25% with each pregnancy; the percentage doesn’t change based on the number of pregnancies ● All states have been screening newborns since 2006 ● Babies are diagnosed at birth typically through a heel prick

Global legalization of marijuana is not a “Yes” or “No” answer. There are negative impacts from marijuana prohibition, and legalization might be a solution, or a partial solution, to a lack of access to essential medicines across the world. So what’s the problem?

Stigmatization ● Sickle cell patients are seen as drug seeking ● Many are young when they present to the er in a pain crisis ● The majority of sickle cell disease patients are African-American, which can add another layer of stigma

● Each country is different ● Each country is impacted by different rules and regulations ● Cannabis is comprised of hemp and marijuana, two separate plants for the most part, at least according to the law. So little is known about hemp and its derivatives, but it has enormous potential in the treatment of pain ● Significant barriers to research? It’s been a Schedule 1 substance

The Impact ● People with sickle cell may have trouble getting and maintaining a job ● Their schooling is affected ● Sickle cell has an impact on the brain, both in development and in early cognitive decline, possibly due to oxygen depravation ● There’s a psychosocial impact; there’s a financial impact ● Patients need help managing their pain crises, and they are frequently mistreated

Frustration: the drug enforcement administration would not entertain moving marijuana or cannabis in general out of Schedule 1 because it had not been studied enough. But it hasn’t been studied enough because it’s in Schedule 1!

A classic Catch-22.

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with

colleen m.

fitzgerald

md, ms

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“I am the oldest of 4 girls, and my father, the biggest feminist I know, taught me to study hard, believe in myself, and that there was nothing I couldn’t accomplish.”

Q

Q

What inspired you to do what you do?

a

Who were your mentors?

a

I always wanted to be a doctor ever since I was a little girl. No one in my family was in medicine but even then I felt it was my vocation, my true calling to take care of the sick and suffering. I am the oldest of 4 girls, and my father, the biggest feminist I know, taught me to study hard, believe in myself, and that there was nothing I couldn’t accomplish. My mother taught me how to listen, to be myself, and to nurture those around me. I chose Physical Medicine and Rehabilitation (PM&r) as my specialty because I was drawn to the focus on quality of life, functional recovery, and maximizing the strengths of the individual even when faced with injury/illness.

My parents, my teachers at Mother McAuley High School, a girls’ Catholic school on the south side of Chicago. Dr. Joanne Smith at Northwestern PM&r introduced me to the field.

She was/is smart, compassionate, strong, a confident definitive leader. Dr. Norm Harden, who taught me most of what I know about pain, and always supported my academic goals. Dr. Joel Press welcomed me into his practice and stood by my quest in women’s health. Urogynecologist Dr. Linda Brubaker taught me efficiency, focus, the value of clinical research, the strength of an interdisciplinary team, and how to keep believing in myself!

Q

Q If you weren’t a healthcare provider, what would you be?

Why did you focus on pain management?

a I was drawn to women’s health. By default as the only female provider in our PM&r musculoskeletal pain practice, many female patients landed in my clinic, a great majority of whom had pelvic pain or pregnancy related pain issues. I couldn’t believe so many of them were still suffering despite having seen multiple providers. I felt compelled to build the practice focusing on pelvic pain/pelvic floor issues. I later pursued clinical research to answer the many questions that lacked sound medical evidence in clinical care.

a

Probably a preschool teacher because I adore children. I’m lucky to have 4 of my own, and I find toddlers to be the best medicine in the world!

Q

a

What is your most marked characteristic?

I think perhaps my compassion. I am drawn to care for all those around me: my patients, my family, my friends.

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“Never give up.

Hold onto your faith and your calling.

Lead by example.

Remain humble.”

Q What do you consider your greatest achievement?

Q

a

I hope to contribute more to the field of pelvic pain with ongoing research in musculoskeletal causes/myofascial pain. Travel. Stay healthy for my children as much as I can, and never retire!

a

Having 4 children and being a Doctor Mom. It is possible!

Q

What is your favorite language?

a

Q

Latin! It’s the basis for much of the language of medicine. My dad made me take Latin in high school and now I don’t regret it. Two of our favorite quotes: Labor omnia vincit—Hard work conquers all Nunquam non quit—Never, never quit

What is your motto?

a

Never give up. Hold onto your faith and your calling. Lead by example. Remain humble.

Colleen M. Fitzgerald, MD, MS, is an Associate Professor at the Loyola University Stritch School of Medicine, and the Medical Director of the Loyola University Medical Center. She is an Ob/Gyn in Maywood, IL.

Q

If you had to choose one book, one film, and one piece of music to take into space for an undetermined amount of time, what would they be?

a

Book: Delia Owen’s Where the Crawdads Sing: such a great read.

Film: The Sound of Music: my all time fav. Julie Andrews never gets old.

Music: Probably some girl power music from Tina Turner, Fergie, Taylor Swift, and lately Lizzo!

Q

Plans for the future?

What would you like your legacy to be?

a

That I trained outstanding physicians in how to care for women in pain, that I raised wonderful children who have their own vocations, that I made a difference in the lives of women with pelvic pain who deserve not to suffer.

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short cuts

By Wendy Caster

Across

1. Simba’s uncle 5. Pass into law 10. Jab 14. Rated G 15. Hue 16. Charge card comp.

17. IT’S GIVEN FOR PAIN CONTROL DURING SURGERY 19. Ready to eat 2 0. Diet soda brand 21. Not hers 22. Moon-crazy?

24. Thrilled 26. Relating to odors or the sense of smell 27. Incurred 29. Traditional 33. More than one 36. French cordial flavoring 38. It’s a knock-out 39. Kudos 41. Not dis 42. Cricket star Suresh Kumar 43. Razzle-dazzle 44. The elevator guy 4 6. A majority 47. Snooze 49. Muse of poetry 51. Tapestry 53. Mucus 57. A bird of prey 6 0. Shrinks’ org.

61. Extinct flightless bird 62. “____ want for Christmas” 63. “NATURE’S ASPIRIN” 6 6. You can believe it’s not butter 67. Lend ___ (listen) 6 8. Court order?

69. Cut 7 0. Old but new again 71. Stout relatives

Down

1. Declare 2. Erie or ear 3. A single-celled animal 4. It can be high or low 5. Spiny anteater 6. Some votes 7. Gore and Pacino 8. Spirals 9. Serious injury 10. FALL: AUTUMN AS ACETAMINOPHEN: ____ 11. Leave out

12. French military cap 13. CFO or CEO 18. Mother of Helios 23. Land-locked African country 25. IT CAN RELIEVE THE PAIN OF A SUBUNGUAL HEMATOMA 26. NARCOTICS 2 8. Reverse 3 0. Birthplace of seven U.S. presidents 31. Contact ____ 32. Darn!

33. Small detail?

34. Black and white aquatic mammal 35. Shed 37. Ruckus 4 0. He gets by with a little help from his friends 45. Japanese beer 4 8. Before the fighting commences 5 0. Melt 52. Skirt type 54. Computer communication

Puzzle solution: painweek.org/crossword.

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55. Pea relative 56. Earns 57. Enemy spy agency in “Get Smart” 5 8. Jazz great Fitzgerald 59. Offed 6 0. Winglike 6 4. Allow 65. Sports ___

Conference snapshot

PAINWeek is the largest, multidisciplinary conference for frontline practitioners. See the tracks, featured sessions, and workshops that comprise the 120+ hours that will be presented over the 5-day conference.

Visit www.painweek.org for the forthcoming Schedule-at-a-Glance/Conference Preview.

Use promo code PWPWJ to receive a $100 discount off the currently published registration fee.

September 8â&#x20AC;&#x201D;12â&#x20AC;&#x201A; 2020 The Cosmopolitan of Las Vegas

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Acute Pain Management

Interventional Pain Management

Advanced Practice Provider

Medical/Legal

American Headache Society

New! Neuromodulation

New! American Society of Interventional Pain Physicians Behavioral Pain Management Cannabinoids

New! Osteoarthritis Research Society International Pain Educators Forum

Chronic Pain Syndromes

Pain Management Coaching

New! Digital Therapeutics

Pharmacotherapy Physical Therapy

Integrative Pain Management

Veterans Health Administration

International Pelvic Pain Society

● Behind the Green Door: Drug Testing Medical Cannabis and cbd in Chronic Pain Patients ● Speaking in Tongues: Guidelines and Paradigms Post-cdc ● Doubling Down: Polysubstance Abuse and Associated Respiratory Depression ● The Opioid Taper Caper: Deciphering and Deflating Daily Dilemmas ● 3 Doors, Lost Keys: Managing Sleep, Depression, and Chronic Pain ● Buped or Duped: Is Buprenorphine for Everyone? ● Narcos: Born in the USA

● The Courtroom Crusades: A 20/20 Examination of Controlled Substance Prescribing Standards ● Drugs, Documentation, and DEA: Improving Your Charting of Prescribing Rationale in 2020 and Beyond ● Puff and Anarchy: Vape Technology and Its Consequences ● The Big Squeeze: Cervical Spondylotic Myelopathy ● Needles & Pins: Medical Acupuncture for Chronic Pain ● Brave New World: Examining cms Guidelines ● The Wild, Wild World of Mathodone: Opioid Conversion Calculations and Methadone Dosing

● The Great Pain Paper Chase: Improving Your Documentation of Patient Selection and Monitoring ● It’s Electric: Emerging Applications for Peripheral Nerve Stimulation for Chronic Pain

● Exiles on Main Street: Complex Cases in Pain Management ● Hardballs, Hard Facts, Hard Choices: Deconstructing the Conundrums of Chronic Pain Management

What is the relay station for reception and processing of nociceptive information?

Education is the best analgesic.

September 8â&#x20AC;&#x201D;12â&#x20AC;&#x201A; 2020 The Cosmopolitan of Las Vegas

Be there or be

Register Now September 8—12 2020 www.painweek.org

The Cosmopolitan of Las Vegas

The next step after ESIs fall short For Lumbar Spinal Stenosis • Removes a root cause of stenosis & leaves nothing behind • Effective in patients with multiple stenosis types & comorbidities1 • Clinically proven to be as safe as an ESI1

To learn more, visit www.Vertosmed.com The complication rate for the mild® procedure is low. As with most surgical procedures, serious adverse events can occur. This procedure is not for everyone. Physicians should discuss potential risks with patients. For complete information regarding indications for use, warnings, precautions, and methods of use, please reference the devices’ Instructions for Use at www.vertosmed.com.

1. Staats PS, Chafin TB, Golovac S, et al. Long-term safety and efficacy of minimally invasive lumbar decompression procedure for the treatment of lumbar spinal stenosis with neurogenic claudication: 2-year results of MiDAS ENCORE. Reg Anesth Pain Med. 2018;43:789-794.

©2020 Vertos Medical Inc. MM-66 Rev 3.0