The Pain Practitioner - The Headache Factor

Integrative Pain Management for Optimal Patient Care

The Pain Practitioner July/August 2017

The Headache Factor + The Power of Virtual Reality

Integrative Management of Sensitized Chronic Pain with Ambulatory Autonomic Self-Regulation Behavioral Interventions for Pain Embrace Technology, Broader Integration into Health Care Systems And More!

TIME TO DUAL

TW O O NE SOURCES SOURCE

OF PAIN OF RELIEF NUCYNTA® ER is the first and only FDA-approved long-acting opioid designed to control both nociceptive pain and the neuropathic pain associated with diabetic peripheral neuropathy (DPN).

Not an actual patient.

Visit Nucynta.com for more information and to download a NUCYNTA® ER savings card

INDICATIONS AND USAGE Limitations of Use NUCYNTA ER is an opioid agonist indicated for the management of: • Because of the risks of addiction, abuse, and misuse with opioids, • pain severe enough to require daily, around-the-clock, longeven at recommended doses, and because of the greater risks of term opioid treatment and for which alternative treatment overdose and death with extended-release opioid formulations, options are inadequate reserve NUCYNTA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate• neuropathic pain associated with diabetic peripheral release opioids) are ineffective, not tolerated, or would be neuropathy (DPN) severe enough to require daily, around-theotherwise inadequate to provide sufficient management of pain. clock, long-term opioid treatment and for which alternative treatment options are inadequate.

• NUCYNTA ER is not indicated as an as-needed (prn) analgesic.

NUCYNTA® ER IMPORTANT SAFETY INFORMATION WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.

• NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow NUCYNTA ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be lifethreatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (5.3).

• Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4), (7).

Please see additional Important Safety Information, including BOXED WARNING, and Brief Summary on the following pages.

NUCYNTA® ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) CONTRAINDICATIONS NUCYNTA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product.

• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extendedrelease products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death.

Opioid are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Life-threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.

To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal

opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol.

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.

Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: NUCYNTA ER treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients.

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs.Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

See Warnings and Precautions in full Prescribing Information for a list of symptoms associated with Serotonin Syndrome.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids.

Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients.

There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics).

Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory

drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

Risks of Use in Patients with Gastrointestinal Conditions NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER. In these patients, mixed agonists/ antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

When discontinuing NUCYNTA ER, gradually taper the dose. Do not abruptly discontinue NUCYNTA ER. Risks of Driving and Operating Machinery NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication.

Risk of Toxicity in Patients with Hepatic Impairment A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER. Risk of Toxicity in Patients with Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known.

ADVERSE REACTIONS In clinical studies, the most common (≼10%) adverse reactions were nausea, constipation, vomiting, dizziness, somnolence, and headache.

NUCYNTAÂŽ ER (tapentadol) IMPORTANT SAFETY INFORMATION (continued) Select Postmarketing Adverse Reactions Anaphylaxis, angioedema, and anaphylactic shock have been reported very rarely with ingredients contained in NUCYNTA ER. Advise patients how to recognize such reactions and when to seek medical attention. Panic attack has also been reported.

DRUG INTERACTIONS Alcohol See BOXED WARNING. Benzodiazepines and Other Central Nervous System (CNS) Depressants See BOXED WARNING. Serotonergic Drugs See Warnings and Precautions.

Monoamine Oxidase Inhibitors (MAOIs) See Contraindications.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics May reduce the analgesic effect of NUCYNTA ER and/or precipitate withdrawal symptoms. Avoid concomitant use.

Muscle Relaxants See BOXED WARNING and Warnings and Precautions.

Diuretics Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when NUCYNTA ER is used concomitantly with anticholinergic drugs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. NUCYNTA ER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.

Labor or Delivery Opioids cross the placenta and may produce respiratory depression in neonates. NUCYNTA ER is not recommended for use in pregnant women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including NUCYNTA ER, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions.

Lactation Because of the potential for serious adverse reactions including excess sedation and respiratory depression in a breastfed infant, advise patients that breast feeding is not recommended during treatment with NUCYNTA ER.

Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use The safety and efficacy of NUCYNTA ER in pediatric patients less than 18 years of age have not been established.

Geriatric Use Elderly patients (aged 65 or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression.

Hepatic Impairment Use of NUCYNTA ER in patients with severe hepatic impairment is not recommended. In patients with moderate hepatic impairment, dosage reduction of NUCYNTA ER is recommended.

Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended.

DRUG ABUSE AND DEPENDENCE See BOXED WARNING OVERDOSAGE In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated.

Cardiac arrest or arrhythmias will require advanced life support techniques.

Please see Brief Summary, including BOXED WARNING, on the following pages.

Š February 2017, Depomed, Inc. All rights reserved. APL-NUCX-0029 Rev. 3

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION This does not include all the information needed to use NUCYNTA ER safely and effectively. See full Prescribing Information for NUCYNTA ER. INDICATIONS AND USAGE NUCYNTA ER (tapentadol) is indicated for the management of: • pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate • neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Limitations of Usage • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations (see Warnings and Precautions), reserve NUCYNTA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

• NUCYNTA ER is not indicated as an as-needed (prn) analgesic.

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.

• NUCYNTA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur.

Monitor closely, especially upon initiation or following a dose increase.

Instruct patients to swallow NUCYNTA ER tablets whole to avoid exposure to a potentially fatal dose of tapentadol. (5.2) • Accidental ingestion of NUCYNTA ER, especially in children, can result in fatal overdose of tapentadol. (5.2) • Prolonged use of NUCYNTA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (5.3).

• Instruct patients not to consume alcohol or any products containing alcohol while taking NUCYNTA ER because co-ingestion can result in fatal plasma tapentadol levels. (5.4) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.4), (7).

CONTRAINDICATIONS NUCYNTA ER is contraindicated in patients with: • Significant respiratory depression • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Hypersensitivity (e.g. anaphylaxis, angioedema) to tapentadol or to any other ingredients of the product (see Adverse Reactions).

• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (see Drug Interactions).

WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse NUCYNTA ER contains tapentadol, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse.

Because extended-release products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present (see Drug Abuse and Dependence).

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).

The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA ER along with intensive monitoring for signs of addiction, abuse, and misuse.

Abuse or misuse of NUCYNTA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of tapentadol and can result in overdose and death (see Overdosage).

Opioid are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing NUCYNTA ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the

proper disposal of unused drug (see Patient Counseling Information). Contact the local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status (see Overdosage). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA ER. To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential (see Dosage and Administration). Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

Neonatal Opioid Withdrawal Syndrome Prolonged use of NUCYNTA ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available (see Use in Specific Populations, Patient Counseling Information).

Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol (see Clinical Pharmacology).

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics (see Drug Interactions).

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when NUCYNTA ER is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs (see Drug Interactions and Patient Counseling Information).

Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: NUCYNTA ER treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER (see Warnings and Precautions).

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients (see Warnings and Precautions).

Alternatively, consider the use of non-opioid analgesics in these patients.

Monitor such patients closely, particularly when initiating and titrating NUCYNTA ER and when NUCYNTA ER is given concomitantly with other drugs that depress respiration (see Warnings and Precautions).

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of tapentadol with serotonergic drugs.

Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic

antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see Drug Interactions). This may occur within the recommended dosage range.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension NUCYNTA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) (see Drug Interactions). Monitor these patients for signs of hypotension after initiating or titrating the dosage of NUCYNTA ER. In patients with circulatory shock, NUCYNTA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of NUCYNTA ER in patients with circulatory shock.

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), NUCYNTA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NUCYNTA ER. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NUCYNTA ER in patients with impaired consciousness or coma.

Risks of Use in Patients with Gastrointestinal Conditions NUCYNTA ER is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The tapentadol in NUCYNTA ER may cause spasm of the sphincter of Oddi.

Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders The tapentadol in NUCYNTA ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during NUCYNTA ER therapy.

Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including NUCYNTA ER. In these patients, mixed agonists/ antagonists and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms (see Drug Interactions).

When discontinuing NUCYNTA ER, gradually taper the dose (see Dosage and Administration). Do not abruptly discontinue NUCYNTA ER (see Drug Abuse and Dependence).

Risks of Driving and Operating Machinery NUCYNTA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NUCYNTA ER and know how they will react to the medication (see Patient Counseling Information).

Risk of Toxicity in Patients with Hepatic Impairment A study with an immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Avoid use of NUCYNTA ER in patients with severe hepatic impairment. Reduce the dose of NUCYNTA ER in patients with moderate hepatic impairment (see Dosage and Administration and Clinical Pharmacology). Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression when initiating and titrating NUCYNTA ER. Risk of Toxicity in Patients with Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment is not recommended due to accumulation of a metabolite formed by glucuronidation of tapentadol. The clinical relevance of the elevated metabolite is not known (see Clinical Pharmacology).

ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse (see Warnings and Precautions) • Life-Threatening Respiratory Depression (see Warnings and Precautions) • Neonatal Opioid Withdrawal Syndrome (see Warnings and Precautions) • Interaction with Benzodiazepine or Other CNS Depressants (see Warnings and Precautions)

• Serotonin Syndrome (see Warnings and Precautions) • Adrenal Insufficiency (see Warnings and Precautions) • Severe Hypotension (see Warnings and Precautions) • Gastrointestinal Adverse Reactions (see Warnings and Precautions) • Seizures (see Warnings and Precautions) • Withdrawal (see Warnings and Precautions) Clinical Trial Experience Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA ER in Patients with Chronic Pain due to Low Back Pain or Osteoarthritis The most common adverse reactions (reported by ≥10% in any NUCYNTA ER dose group) were: nausea, constipation, dizziness, headache, and somnolence.

The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA ER dose group for NUCYNTA ER- and placebo-treated patients were nausea (4% vs. 1%), dizziness (3% vs. <1%), vomiting (3% vs. <1%), somnolence (2% vs. <1%), constipation (1% vs. <1%), headache (1% vs. <1%), and fatigue (1% vs. <1%), respectively.

Please see full Prescribing Information for ADRs occurring in ≥ 1% of patients.

Commonly-Observed Adverse Reactions in Clinical Studies with NUCYNTA ER in Patients with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The most commonly reported ADRs (incidence ≥10% in NUCYNTA ER-treated subjects) were: nausea, constipation, vomiting, dizziness, somnolence, and headache.

Please see full Prescribing Information for ADRs occurring in ≥ 1% of patients.

Postmarketing Experience The following adverse reactions have been identified during post approval use of tapentadol.

Psychiatric disorders: hallucination, suicidal ideation, panic attack Serotonin syndrome: Cases of serotonin syndrome, a potentially lifethreatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in NUCYNTA ER. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids (see Clinical Pharmacology).

DRUG INTERACTIONS Clinically Significant Drug Interactions with NUCYNTA ER Alcohol Clinical Impact:

Concomitant use of alcohol with NUCYNTA ER can result in an increase of tapentadol plasma levels and potentially fatal overdose of tapentadol.

Intervention: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy.

Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Due to additive pharmacologic effect, the concomitant use of Impact: benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5.4)].

Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.

Serotonergic Drugs Clinical The concomitant use of opioids with other drugs that affect Impact: the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions 5.6].

Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

Discontinue NUCYNTA ER if serotonin syndrome is suspected.

Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Monoamine Oxidase Inhibitors (MAOIs) Clinical MAOI interactions with opioids may manifest as serotonin Impact: syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2)].

Intervention: Do not use NUCYNTA ER in patients taking MAOIs or within 14 days of stopping such treatment Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical May reduce the analgesic effect of NUCYNTA ER and/or Impact: precipitate withdrawal symptoms.

Intervention: Avoid concomitant use.

Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Tapentadol may enhance the neuromuscular blocking action of Impact: skeletal muscle relaxants and produce an increased degree of respiratory depression.

NUCYNTA ER (tapentadol) extended-release tablets, CII BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION (continued) Muscle Relaxants (continued) Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of NUCYNTA ER and/or the muscle relaxant as necessary.

Diuretics Clinical Opioids can reduce the efficacy of diuretics by inducing the Impact: release of antidiuretic hormone.

Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs Clinical The concomitant use of anticholinergic drugs may increase Impact: risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when NUCYNTA ER is used concomitantly with anticholinergic drugs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome (see Warnings and Precautions).

The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications.

Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly (see Warnings and Precautions).

Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psychphysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. NUCYNTA ER is not recommended for use in pregnant women during and immediately prior to labor. Opioid analgesics, including NUCYNTA ER, can prolong labor.

Lactation Risk Summary There is insufficient/limited information on the excretion of tapentadol in human or animal breast milk. Physicochemical and available pharmacodynamic/toxicological data on tapentadol point to excretion in breast milk and risk to the breastfeeding child cannot be excluded.

Because of the potential for serious adverse reactions including excess sedation and respiratory depression in a breastfed infant, advise patients that breast feeding is not recommended during treatment with NUCYNTA ER. Clinical Considerations Monitor infants exposed to NUCYNTA ER through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use The safety and efficacy of NUCYNTA ER in pediatric patients less than 18 years of age have not been established.

Geriatric Use Of the total number of patients in Phase 2/3 double-blind, multiple-dose clinical studies of NUCYNTA ER, 28% (1023/3613) were 65 years and over, while 7% (245/3613) were 75 years and over. No overall differences in effectiveness or tolerability were observed between these patients and younger patients.

Elderly patients (aged 65 or older) may have increased sensitivity to tapentadol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of NUCYNTA ER slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression (see Warnings and Precautions).

Hepatic Impairment Use of NUCYNTA ER in patients with severe hepatic impairment (ChildPugh Score 10-15) is not recommended. In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), dosage reduction of NUCYNTA ER is recommended (see Dosage and Administration).

Renal Impairment Use of NUCYNTA ER in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) is not recommended.

DRUG ABUSE AND DEPENDENCE Controlled Substance NUCYNTA ER contains tapentadol, a Schedule II controlled substance.

8

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

Abuse NUCYNTA ER contains tapentadol, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone. NUCYNTA ER can be abused and is subject to misuse, addiction, and criminal diversion (see Warnings and Precautions).

The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers, and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

NUCYNTA ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of NUCYNTA ER NUCYNTA ER is for oral use only. Abuse of NUCYNTA ER poses a risk of overdose and death. The risk is increased with concurrent use of NUCYNTA ER with alcohol and other central nervous system depressants.

With intravenous abuse the inactive ingredients in NUCYNTA ER can result in local tissue necrosis, infection, pulmonary granulomas, embolism and death, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

NUCYNTA ER should not be abruptly discontinued (see Dosage and Administration). If NUCYNTA ER is abruptly discontinued in a physicallydependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see Use in Specific Populations).

OVERDOSAGE Clinical Presentation Acute overdosage with NUCYNTA ER can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.

Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.

© May 2017, Depomed, Inc. All rights reserved. APL-NUCX-0249

The Pain Practitioner JULY/AUGUST 2017

To access the virtual magazine, go to newsstand.aapainmanage.org

10 NOTES FROM THE FIELD Chronic Pain: Symptom or Disease?

By Bob Twillman, PhD, FAPM, Executive Director 11 EDITORIAL When 2 Percent Is Everything

By W. Clay Jackson, MD, DipTh, Editor-in-Chief PAGE 10

12 ANNUAL MEETING/EDUCATION Presence, Patience, and Perseverance: A Veteran’s Story By Debra Nelson-Hogan 13 Annual Meeting Schedule-at-a-glance 14 ADVOCACY Pain Care Policy Offerings at the Annual Meeting 15 A Bird’s Eye Review of Headache Pathophysiology and Treatment

By Jason N. Harris, MD

PAGE 12

18 New Developments in the Pharmacologic Treatment of Chronic Migraine: A Summary of Recent Clinical Trial Results

By Christine Rhodes, MS 20 The Power of Virtual Reality

By Christine Rhodes, MS

PAGE 18

23 Integrative Management of Sensitized Chronic Pain with Ambulatory Autonomic Self-Regulation

By JP Ginsberg, PhD 26 Behavioral Interventions for Pain Embrace Technology, Broader Integration into Health Care Systems

By Debra Nelson-Hogan 28 What is Photobiomodulation?

By Ernesto Cesar Pinto Leal-Junior, PhD, and Douglas Johnson, ATC

PAGE 28

And More, on the Web...

We’re on Social Media! Connect with us for the latest news in integrative pain management:

Follow us on Twitter @aapainmanage

Like us on Facebook facebook.com/aapainmanage

Watch us on YouTube youtube.com/c/Aapainmanage OrgAAPM

Connect on LinkedIn linkedin.com/company/ american-academy-of-pain-management

Add us on Google+ plus.google.com/ u/0/+AapainmanageOrgAAPM

28th Annual Meeting This issue highlights faculty presenting at the annual meeting:

W. Clay Jackson, MD, DipTh, Page 11 Col. Gregory Gadson (Retired), Page 12 Brenda Weiderhold, PhD, Page 20 JP Ginsberg, PhD, Page 23 Beth Darnall, PhD, Page 26 Subscribe to The Pain Practitioner even if you are not a member... you can still get this bi-monthly publication for just $50 annually!

Send your check to the Academy of Integrative Pain Management, 8700 Monrovia Street, Suite 310, Lenexa, KS 66215

Academy of Integrative Pain Management

www.integrativepainmanagement.org

ACADEMY BOARD OF DIRECTORS President Joanna Katzman, MD, MSPH Past President Robert A. Bonakdar, MD, FAAFP Vice President W. Clay Jackson, MD, DipTh Secretary Paul Christo, MD, MBA Treasurer Kevin T. Galloway, BSN, MHA, Colonel, US Army (Retired) Directors-at-Large Alfred V. Anderson, MD, DC George D. Comerci, Jr, MD, FACP John Garzione, DPT Christian D. González, MD Michael Kurisu, DO, ABIHM Joseph Matthews, DDS, MSc Liaison to the Board Maggie Buckley

STAFF AND CONSULTANTS Executive Director Robert Twillman, PhD, FAPM Director of the State Pain Policy Advocacy Network (SPPAN) Amy Goldstein, MSW Assistant Director of Education Cathleen Coneghen Director of Legislative and Regulatory Affairs Katie Duensing, JD Member Services Manager Whitney O’Donnell Account Manager Rosemary LeMay Professional Development Project Manager MacKenzie Davis Content Consultant Debra Nelson-Hogan

THE PAIN PRACTITIONER STAFF AND CONSULTANTS Editor-in-Chief W. Clay Jackson, MD, DipTh Editor Debra Nelson-Hogan Advertising and Sales Leslie Ringe Managing Editor Cathleen Coneghen Clinical Editor Christine Rhodes, MS Art Director Peter McKinley, Pak Creative Copy Editor Rosemary Hope

The Pain Practitioner is published by the Academy of Integrative Pain Management, P: 209-533-9744, Email: aapm@integrativepain.org, website: www.integrativepainmanagement.org.

Copyright 2017 Academy of Integrative Pain Management. All rights reserved.

Send correspondance to: Debra NelsonHogan at dhogan@integrativepain.org.

For advertising opportunities, media kits, and prices, contact: sales@integrativepain.org or 209-533-9744.

The Pain Practitioner is published by the Academy of Integrative Pain Management solely for the purpose of education. All rights are reserved by the Academy to accept, reject, or modify any submission for publication.

The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of the Academy or individual members. The Academy does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. The Academy of Integrative Pain Management does not assume any responsibility for injury arising from any use or misuse of the printed material contained herein. The printed material contained herein is 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 the Academy to accept, reject, or modify any advertisement submitted for publication. It is the policy of the Academy to not endorse products. Any advertising herein may not be construed as an endorsement, either expressed or implied, of a product or service.

NOTES FROM THE FIELD

Chronic Pain: Symptom or Disease?

Why Does It Matter?

By Bob Twillman, PhD, FAPM, Executive Director

Frequently, I hear medical experts and policymakers talk about prescribing opioids for people with “chronic noncancer pain.”

I’ve always thought that terminology was unhelpful, for two reasons: first, I’m unsure that we should be excluding pain related to cancer from these discussions; and second, I don’t think “noncancer pain” is a single entity for which there can be a blanket opioid prescribing recommendation, or policy. Noncancer pain consists of dozens, if not hundreds, of painful conditions with a wide variety of causes and an equally wide variety of effective treatments. To treat every type of noncancer pain as if it is the same as all the others is a logical error that may result in many patients being inappropriately treated.

In thinking more about this, and about what types of chronic noncancer pain (CNP) might be more or less responsive to opioid therapy, I’ve reviewed my clinical experience and usually landed upon arthritis and sickle cell disease as opioid-responsive conditions, and fibromyalgia, low back pain, and headache as opioid-nonresponsive conditions. But I’ve struggled to derive from these specific examples a general rule that might help clinicians decide whether to consider opioid therapy for a given patient.

THE SYMPTOM VS. DISEASE DEBATE I’ve also struggled a bit with the debate about whether chronic pain is properly considered a symptom or a disease.

Some believe that it is “just” a symptom, something that won’t cause further harm to the person experiencing it. Others have argued that chronic pain induces changes in the body that can, indeed, lead to

10

further illness and even death, making it a disease. In my view, this discussion might be missing the mark in the same way that the discussion about whether opioids should be used to treat CNP is misguided.

So, you might ask, in my opinion, is CNP a symptom or a disease? My answer: Yes. Yes, it is.

I think CNP can sometimes be a symptom and that it can sometimes be a disease.

Sometimes, it’s both, in the same person.

Let me see if I can explain in a reasonably clear and concise manner, and after you’ve read this, feel free to email me to let me know if you think I’ve missed the mark.

When CNP is a symptom (CNP-S), it has the following characteristics: An identifiable peripheral pain generator creates a signal that propagates through an intact, normally functioning nervous system, and is then interpreted by the individual as representing pain. CNP-S is the body acting exactly as it should under the circumstances. As is also true of acute pain, CNP-S is adaptive because it informs the person experiencing it that there is something amiss somewhere in his or her body.

Examples of CNP-S are pain from arthritis and from ischemic damage due to sickle cell disease.

On the other hand, when CNP is a disease (CNP-D), there is no identifiable peripheral pain generator, or, if there is an identifiable peripheral event, it is insufficient to produce pain in a person with an intact, normally functioning nervous system. The nervous system is either injured or sensitized to such a degree that normally non-painful stimuli produce pain. The key element is that the nervous system is not functioning in a normal manner (i.e., it is diseased) and the pain is no longer adaptive, but maladaptive.

It is possible for one person to simultaneously experience both CNP-S and CNP-D. We know that prolonged CNP resulting from a peripheral pain generator can sensitize the nervous system, resulting in amplification of the pain and the development of allodynia and/or hyperalgesia. In such a case, the CNP is a symptom-disease syndrome.

HOW THIS INFORMS TREATMENT For CNP-S, the primary focus of treatment should be modifying or eliminating the peripheral pain generator, and sec-

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

ondarily modulating the nervous system to dampen or block the signals that produce pain. For CNP-D, the primary focus of treatment shifts to modulating the nervous system so that normal stimuli don’t produce pain.

When I review my clinical experience and think about patients whose CNP responded well to opioids, it’s typically patients with CNP-S. My experience is that opioids are much less useful, and are generally best avoided, when treating CNP-D. Opioids work well in an intact normally functioning nervous system, but not in one that is functioning abnormally.

I think this schema also may work for non-opioid pharmacological treatments: NSAIDs are primarily helpful for CNP-S, while anticonvulsants are primarily helpful for CNP-D. And I think it might work for non-pharmacological treatments. To the extent that we can say whether a given non-pharmacological treatment primarily modifies peripheral pain generators or modulates nervous system dysfunction, we can select among those treatments on that basis. However, I think the case can be made that many non-pharmacological treatments affect both peripheral generators and the nervous system, so perhaps they really represent what we might call “broad spectrum” pain treatments.

Perhaps that is why they are so extraordinarily useful in treating all types of chronic pain, and why the mantra “never only opioids” is spot-on.

There’s a lot more that could be done to develop this concept, but before proceeding, I welcome your thoughts on the matter. Does the CNP-S/CNP-D distinction make sense? Does it really help inform treatment planning? Or am I completely off base? Contact me with your thoughts at btwillman@integrativepain.org.❏ Bob Twillman, PhD, is the executive director for the Academy of Integrative Pain Management.

Dr. Twillman is responsible for overseeing federal and state pain policy developments and advocating for those supporting an integrative approach to managing pain. He also serves as Chair of the Prescription Monitoring Program Advisory Committee for the Kansas Board of Pharmacy.

EDITORIAL

When 2 Percent Is Everything

By W. Clay Jackson, MD, DipTh, Editor-in-Chief

She was a handful. Now wait, don’t report me to the patient advocacy officer just yet.

She would tell you herself—proudly—that she was a handful, and give a toothy, impish grin as if to prove it. I first started seeing her about 15 years ago for bipolar disorder. In the South, as with a good portion of the rest of the country, primary care physicians provide the lion’s share of mental health services. As Anna’s family physician, her mood swings, irritability, and anxiety therefore fell to me to treat. We did okay. She got better, built a solid marriage and a number of enduring friendships, and stayed employed. Considering the natural history of the disease, I was pleased.

Then came the breast cancer. Metastatic adenocarcinoma sounds ominous enough to rattle any patient’s equanimity, and Anna was fragile. Her oncologist reached out to me to see her again, this time in my role as a palliative care consultant working in an adjunct capacity in a large, multispecialty cancer center. We worked through the challenges, two or three at a time. There was the chest pain, the bone pain, the nausea, the weight loss, and (oh, yes) the anxiety and depression associated with her significant change in health status.

Fortunately, Anna responded to her cancer-directed therapy with regression of disease. She also responded brilliantly to her palliative treatment. With breathing exercises, meditation, gabapentinoids, and a sprinkling of opioids, her pain was greatly reduced. In addition, her anxiety was controlled, and she was able to go back to work. Once her tumor burden dropped, and the chemotherapy was stopped, the nausea resolved.

But then the nagging headaches came.

She mentioned it as an afterthought, because it seemed more of a nuisance compared to the gravity of her primary diagnosis and all its attendant challenges. The history was of a fairly continuous pain at the back of the head, without visual changes or nausea. I examined her; she had no neurologic deficit. When I pressed on her occiput, she was markedly tender over the distribution of both occipital nerves.

“We got this!” I exclaimed. “I’m 98% sure I know what’s wrong with you, and if I’m right, we can make you feel better in minutes!” I was excited, and for a number of reasons. Mainly, because I felt that I had a nonmalignant etiology of her headaches nailed—occipital neuralgia. But partially,

because I was proud that I had learned a new skill at our last Academy meeting, namely an occipital block, and I was confident I could help my patient.

“Okay, Anna. We’re going to give you a couple of shots in the back of your scalp … Stop making that face! You want to feel better, don’t you?” After informed consent, I performed a bilateral occipital block, and Anna’s relief was complete and immediate.

I beamed as she said, ”Wow! My headache is gone!”

Old habits die hard, though. I had a presumptive diagnosis, and a patient whose symptoms had responded beautifully to empiric treatment. But I also had a patient with a history of metastatic disease, who had a persistent headache. What I had told her was true—I was 98% sure that we weren’t dealing with metastatic disease.

But 2% is a truckload of uncertainty, when cancer is in play for a young woman who has trusted you with her life.

“Hey, Anna. One more thing. I’m pretty sure this is overkill, but I need to check your head with a CT scan. Don’t be worried.

We just need to be sure.”

An hour later, my emotions, and Anna’s, had run the full gamut. She had a cerebellar metastasis, and the positive response to our occipital block was revealed for what it was—a potential red herring that could have cost her dearly. We set her up with neurosurgery for a metastectomy, which fortunately was successful.

Anna’s headaches are still better. She’s still fighting on, successfully. She’s still a handful, and proud of it. She still believes in me as her doctor—that I care, and that I’m paying attention.

And I’m still learning to deal with the 2%. ❏ W. Clay Jackson, Editor-in Chief, is clinical assistant professor of family medicine and psychiatry at the University of Tennessee College of Medicine in Memphis, Tennessee, where he maintains a private practice in family and palliative medicine. He is also the medical director of Comprehensive Primary Care, and of Methodist Hospice and Palliative Services. Dr. Jackson is the associate fellowship director of palliative medicine at the University of Tennessee College of Medicine.

400

@

THE 28TH ANNUAL MEETING See Dr. Jackson present the keynote, “Wounded Healers: Preventing Clinician Suicide’ and the session “ChemotherapyInduced Neuropathic Pain: Victories and Defeats” at the 28th Annual Meeting in San Diego.

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

11

ANNUAL MEETING/EDUCATION

Presence, Patience, and Perseverance: A Veteran’s Story

By Debra Nelson-Hogan, Editor, Pain Practitioner

Col. Gregory D. Gadson, USA (retired) learned a lot about resilience and being in the moment during his recovery from an improvised explosive device (IED) attack in Iraq that cost him both legs above the knees and normal use of his right arm and hand. As a career military officer and a former college football player for West Point, he is a hard-wired team player, all of which give him an appreciation for team-based, integrative pain care.

After his recovery, Col. Gadson remained on active duty in the Army and held several key positions.

In 2007, Tom Coughlin, New York Giants head coach, asked Col. Gadson to meet with the then-struggling team. Gadson talked to the players about service, teamwork, duty, perseverance and adversity.

His message resonated and the New York Giants defeated the 18-0 New England Patriots in Super Bowl XLII. Also, he made his film debut in “Battleship,” where he played a war-injured veteran who helped save the world from an alien invasion and in 2015 he was in a TV series. Today, Col. Gadson is an entrepreneur and a motivational speaker.

So it makes perfect sense for him to open the AIPM Annual Meeting in San Diego in October.

Col. Gadson inspires many with his message of courage, perseverance, determination, and teamwork and he is no stranger to pain. He experiences first hand the challenges of a double amputee, including the phantom limb pain that other amputees experience. “I have pain in my calf and feet, and it registers a 1 or 2 on a scale of 10,” he says. The pain is manageable with battlefield acupuncture treatments every few weeks. And although the relief is short lived, it is still relief when the pain spikes, he says. Acupuncture is the only treatment he uses for pain. Col. Gadson looks at the

12

pain as part of his condition. “I don’t fight it. I just roll with it,” he says.

“I live with pain,” he says. “I would like to be operating at 100% capacity, but I accept that I function at about but 85%.

That is pretty good.” His experience with the medical system gave him a new appreciation for integrative care. “Some physicians are very open minded and others less open minded to nontraditional

have to play the play I’m in. I can’t redo the last play and can’t think of the next one.”

He appreciates everything around him and says that life has unveiled unimaginable opportunities. He continues, “If I stay in the moment and just do my best and don’t worry about tomorrow, that is all I can do.

It is part of my resiliency. My character.”

Another profound change? “I smile more. I don’t take things so seriously. It is

forms of medicine, i.e., not open minded to acupuncture. Along the spectrum of treatment, I want to encourage the care team to open its mind to other possibilities,” Col. Gadson notes.

When asked the most profound change in his life in the last 10 years, he says learning to live in the present has been so valuable. “When I was injured and in recovery, it took all of my energy to stay in the moment and just heal. I invested all of my energy in ‘today.’ I couldn’t begin to imagine what was over the horizon. Thinking about tomorrow was not possible.” In many ways, this idea of staying in the present is perfectly aligned with playing football. “I

a major lesson learned. Because I’ve been through the fire, I look at life with a different lens and appreciate life in a way that I may not have otherwise,” he says. Col. Gadson leads an active life, with cycling and wheelchair basketball and although he wishes he could do better, he is philosophical about his status.

When he accepted his ring for his role in the Giant’s Super Bowl win, Col. Gadson told the crowd, “This path wasn’t what I envisioned, but it has brought me here.”

His message is powerful for everyone who has major life changes—and most of us do—but particularly for those with chronic pain. ❏

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

ANNUAL MEETING/EDUCATION

THE 28TH ANNUAL MEETING

Schedule At-a-Glance Thursday, October 19

Saturday, October 21

Sunday, October 22

Keynote: Presence, Patience, and Perseverance: A Veteran’s Story US Army COL (Ret) Gregory D. Gadson

Keynote: The Science, Politics and Medicine of Medical Cannabis for Chronic Pain Mark Wallace, MD The clinical evidence – and challenges – for treating pain with medical cannabis.

4-hour Workshop: The Nuts and Bolts for a Successful Integrative Pain Management PracticeTraumatic Brain Injury

President’s Welcome & Reception W. Clay Jackson, MD, DipTh, President of AIPM

Friday, October 20 Keynote: Pain in the Brain VS Ramachandran, MD, PhD Fibromyalgia: Best Practices for Integrative Treatment Approaches Mind-Body Therapies for Pain and PTSD in the Military Setting How mind-body medicine has become an integral component of health care in the military.

CRPS Case Study Session: Fibromyalgia Connecting Foods with Symptoms: The Allergy Elimination Diet and Pain Uncovering hidden food allergies and sensitivities through an elimination diet Virtual Reality is a Reality – and It’s Helping Chronic Patients Right Now Decades of research have now made this technology a helpful tool in patient care.

Technology Showcase: Bringing Your Practice into the 21st Century Low Risk, High Success: Prolotherapy for Regenerative Medicine for Osteoarthritis The science behind regenerative injections Orofacial Neuropathy: Appropriate Diagnosis and Treatment Conference Assembly: Interdisciplinary Functional Restoration Programs for Chronic Pain Migraine: It Doesn’t Have to be a Headache Case Study Session: Migraine Chemotherapy-Induced Neuropathic Pain: Victories and Defeats Back by Popular Demand!

Hormone Therapy for Pain Management Using hormones to treat the underlying microglial activation, neuroinflammation, and neurodegeneration.

A Common Condition You Haven’t Heard Of: Small Fiber Polyneuropathy Case Study Session: Small Fiber Polyneuropathy Technology and Physical Medicine Advanced Medication and Procedural Options for Headache Insomnia and Pain: Nonpharmacological Solutions Integrative Options for Headache: Out of the Medicine Cabinet and Into the Pantry Non-pharmacological approaches to treating headache such as nutrition, biofeedback, herbs, and supplements.

Non-Invasive Treatments for Low Back Pain and ACP Guidelines The 3 E’s of Patient Communication: Empathy, Education and Engagement to Improve Outcomes Identifying and Managing the Red Flags of Opioid Misuse Using a synergistic integrated team approach to combat the opioid epidemic Team-based Care for Low Back Pain: A Panel Discussion The Moral Debate: Do What’s Right – Or What’s Allowed?

The impact of moral distress on pain management practices Food as Treatment: Luncheon and Cooking Demonstration

Medical Acupuncture Is Systemic Lidocaine the New Standard of Care for Pain Due to Inflammation?

The Integrative Road Less Traveled: Autonomic Dysfunction and Headache “Unlearning” Chronic Pain: Ground-breaking Concepts in Neuroscience, Medicine and Psychology for Pain Elimination Lessons from Chiropractic Medicine: Using Fewer High-Risk Drugs for Low Back Pain Retraining the Pain Brain—Sensory Biofeedback It’s Not In Your Head: Biological Rationales of Psychological Treatment for Chronic Pain

Enhanced Recovery After Surgery (ERAS) Keynote: Wounded Healers: Preventing Clinician Suicide W. Clay Jackson, MD, DipTh Conference Assembly: Regulatory and Access Realities Osteoarthritis: Assessment, Diagnosis, Treatment, Effectiveness and Team Member Engagement The Evidence for Chronic Opioid Therapy for Chronic Pain Case Study Session: Osteoarthritis Research on Evidence on Integrative Medicine An Evidence-Based Need: Urine Drug Monitoring

How to Reboot the Body to Release Stress Keynote: Changing Mindsets to Enhance Pain Treatment Effectiveness Beth D. Darnall, PhD Integrative Pain Care Policy Congress (Invite Only) Patient Day

Hilton San Diego Bayfront San Diego, California October 19-22, 2017

For a list of faculty and a hour-by-hour schedule, visit http://www.integrativepainmanagement.org/page/annualmeeting To register, go to:

http://www.integrativepainmanagement.org/event/2017

Poster Abstract Presentations THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

13

ADVOCACY

Pain Care Policy Offerings at the Annual Meeting As the only pain management organization with a full-time policy team, we know better than most that pain policy is changing at a breakneck pace.

In the first six months of 2017, aIPm's policy team tracked 1,200 bills 200 regulations

sent more than

80

letters aiming to influence 70 policy proposals in 30 states and federally

We hope to see you in San Diego!

Want to learn more about the policies that affect your practice and your patients? Join us at AIPM’s

Visit the AIPM booth in the exhibit hall to meet the team responsible for advocating on your behalf!

Annual Meeting in San Diego October 19-22, 2017!

Amy Goldstein, MSW, SPPAN Director

Bob Twillman, PhD, FAPM, Executive Director (former Director of Policy and Advocacy)

Katie Duensing, JD, Director of Legislative and Regulatory Affairs

Don’t miss these policy opportunities in San Diego!

“Payment Realities for Integrative Pain Care”

will teach clinicians about efforts to develop reimbursement models that support evidence-based and cost-effective comprehensive pain management encompassing both pharmacologic and nonpharmacologic treatment modalities. We will hear from a private payer and CMS about the process by which they make determinations for coverage.

14

“What’s Appropriate— and What’s Not? Safe Opioid Prescribing in a World of Ever-Changing Regulations” is a 6-hour

workshop taught by Paul Christo, MD, and Jen Bolen, JD, that will help clinicians to deliver optimal pain care to their patients while protecting themselves and their practices from regulatory action and litigation.

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

AIPM/SPPAN’s inaugural Integrative Pain Care Policy Congress is being

held October 21-22 in San Diego.

To chart a collective path forward in regard to advancing integrative pain care, this by-invitation meeting will bring together leaders and experts representing the full scope of licensed and certified health care professionals involved in pain care, along with insurers, regulators, people with pain, researchers, and policy experts.

A Bird’s Eye Review of Headache Pathophysiology and Treatment

By Jason N. Harris, MD

tion” at the site of the trigeminal afferents at the meninges, (see migraines below) also activating the trigeminothalamic pain network (3). Vasoconstriction and vasodilation of the cranial vessels (innervated by the trigeminal nerve) can be associated with activation of this network (4). At the center of the trigeminothalamic pain network are the trigeminal nuclei (5). They extend from the midbrain (mesencephalic portion) through the pons (principal sensory nucleus) down through the medulla and into the upper cervical cord (spinal nucleus of V). Adjacent to these nuclei are numerous other autonomic, cranial nerve nuclei and cervical afferents. This being the case, there can be a significant amount of communication or “cross talk” between these (6-8). This may explain why with some headache disorders, there can be autonomic (e.g., Horner’s syndrome) or cervical involvement (9).

For us to consciously perceive pain, the trigeminal nucleus must communicate its activation to the cortex via the thalamus (10, 11). As pain is continuously perceived, “central sensitization” begins to take effect (12-14). When this occurs, we become more prone to perceiving the painful stimulus than normal stimuli. This can remain the case even when the stimulus from the trigeminothalamic network decreases or even ceases. In such cases a multidisciplinary approach to management, including behavioral health, can be of great benefit (15).

When a patient first presents with headaches, it is important to consider “benign” primary disorders vs. more worrisome secondary (and potentially life-threatening) headache disorders.

Red flags should be looked for in the history, review of systems, neurological exam, and, at times, imaging and laboratory studies.

Once worrisome secondary headaches have been appropriately ruled out, primary headaches can be considered.

There are over 100 types of headaches that share many pathophysiological mechanisms (1). The trigeminothalamic pain network is the “hub” of headache disorders and can be activated in a variety of ways, which in turn can interact with other brainstem nuclei as well as cervical afferents creating many of the different clinical headache subtypes. Central sensitization occurs as headaches endure and is an important mechanism to understand.

This article provides a “bird’s eye” view of headache pathophysiology shared by many headaches as well as some basic diagnostic and management paradigms.

BASIC HEADACHE PATHOPHYSIOLOGY I like to think of the trigeminothalamic pain network as the central hub of headache disorders (2). When activated, we experience headache. Trigeminal afferents innervate the cranial blood vessels, the sinuses, and the meninges as well as other structures of the skull and head (2, 3). The gray and white matter of the brain itself is insensate. If there is any type of infection, inflammation, trauma, or metabolic insult that stimulates these trigeminal afferents, the trigeminothalamic pain network will likely be activated.

Cortical spreading neuronal depressions are a local metabolic/ electrochemical event that can also trigger a “sterile inflamma-

SOME COMMON PRIMARY HEADACHE DISORDERS AND THEIR MANAGEMENT Migraines: Patients with migraines tend to have brains that are more electrochemically “hyperexcitable.” There is evidence that the initiating event in migraines is a cortical spreading depression (CSD). This is a wave of electrical hyperexcitability followed by a wave of hypoexcitability traveling across the cortex, usually at about 3 mm/minute. This is often experienced as the subjective migrating aura of a classic migraine. If it occurs across the occipital cortex, migrating visual auras result. If it occurs across the parietal cortex, migrating sensory auras ensue. If the CSD travels across a “silent” area of the brain, an aura may not be experienced at all, though evidence of the CSD still may be seen on functional imaging (16). CSDs usually last no longer than 60 minutes, though there are exceptions. Classically, CSDs cause a “sterile inflammation” in the meninges which then activates the trigeminothalamic pain network with a headache then following.

If the sterile inflammation is not sufficient to activate the trigeminothalamic pain network, the patient may experience “acephalgic migraines” (auras without subsequent headaches) (5,17-19).

I find a few International Headache Society (IHS) diagnostic criteria to be particularly helpful once more worrisome headache etiologies have been ruled out. If the patient has experienced five or more severe headaches without aura and the headaches last THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

15

4 to 72 hours (without treatment or unsuccessful treatment), are pulsating or unilateral, are worsened by activity, and more worrisome etiologies have been ruled out AND there is nausea, it is a migraine. Or, if there is photophobia AND phonophobia, it is a migraine. If the headaches are preceded by an aura lasting 5 to 60 minutes, the individual has had at least two of these headaches, and more worrisome etiologies are ruled out, it is a migraine (1).

Migraine treatments can be thought of as being on two tiers, abortive and prophylactic. To work best, acute migraine treatments should be given at the onset of a migraine before “central sensitization” has set in. Triptans, acetaminophen, and NSAIDS such as ibuprofen, naproxen and ketorolac can work very well for this purpose. Opioids should not be routinely used as they frequently deepen central sensitization in the long run and complicate migraine treatment. Abortive agents used more than two to three times a week can trigger analgesic overuse headaches.

In fact, as few as five doses a month of the acetaminophen/ butalbital/caffeine combination can also trigger analgesic overuse headaches (20).

If a patient is having more than one migraine a week, or is having extremely debilitating migraines, prophylactic therapy should be considered. There are good data supporting amitriptyline, propranolol, topiramate, valproic acid, and venlafaxine as prophylactics. Magnesium oxide and riboflavin can also be of benefit as prophylactic agents (21). There are data supporting the herbal agent butterbur as well but I usually avoid it as it can be teratogenic (22,23). Common pitfalls in prescribing prophylactics are dosing amitriptyline too high (best to start at 10 mg PO QHS or even 5 mg PO QHS) or dosing propranolol too low (it often takes at least 120 mg daily to work for migraine prophylaxis). Prophylactics often take up to a month or more to begin to take effect.

Patients with chronic daily migraines (more than 15 days a month) who are unresponsive to traditional oral prophylactics can also be offered onabotulinumtoxinA injections (24).

Though tension headaches have their own IHS classification (1), they are thought of by most neurologists as being along the same pathophysiological continuum as migraines, and respond to the same treatments. I find a few of the IHS criteria particularly helpful. If a headache is mild to moderate in severity and other secondary etiologies have been ruled out, there is a very good chance it is a tension headache. Tension headaches are usually bilateral, but they don’t have to be. If they are associated with nausea or auras, or if both phonophobia and photophobia are present, they aren’t tension headaches. Tension headaches will often occur with photophobia or phonophobia, but not both.

Some clinicians think of “tension” headaches as being caused by “tension” in the muscles of the neck and scalp. It is not clear this is the case however. Accompanying “muscle tension” may be more a result of the “cross talk” between the trigeminal nuclei and cervical afferents (see above) (25). Interestingly, the prophylactic agents with the best data for preventing tension headaches are NOT muscle relaxants but are those used for treating migraines.

Amitriptyline is considered a first line therapy for prophylaxis of tension headaches. Topiramate is also effective. Over the counter analgesics typically work well for the acute treatment of tension headaches, provided they are not used more than two or three days a week, which can lead to medication overuse headache (26).

Cluster headaches are unilateral, SEVERE, orbital/supraorbital and/or temporal headaches, but tend to be overdiagnosed. The ophthalmic nerve innervates most of the meninges and meningeal blood vessels as well as the ocular structures (27). Referred pain to or around the eye is therefore common with many headache

16

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

disorders. However, unilateral pain around or in the eye with headaches does not mean it is a cluster headache! A key differentiating point is that as opposed to migraines, patients with cluster headaches typically find some relief with activity. They will typically be pacing the floor for relief when the headache occurs.

Cluster headaches come in “clusters,” usually depending on the season or time of year. They can occur every other day or up to eight times a day and last 5 to 180 minutes (1,28). They are almost always associated with autonomic features such as transient Horner’s syndrome, conjunctival injection, or lacrimation (there may be communication between trigeminal nuclei and other ipsilateral autonomic nuclei). They frequently occur at night and will often wake patients. In cases when cluster headaches are suspected, particularly “new onset,” vascular etiologies such as dissection and subarachnoid hemorrhage (or even giant cell arteritis (GCA) depending on history) should also be strongly considered. Of course, it is also prudent to consider ocular entities such as acute angle closure glaucoma, uveitis, or iritis. Triptans and high-flow oxygen therapy can work well as acute treatments for cluster headaches. Verapamil and valproic acid are classic prophylactics for cluster headaches (29).

Finally, occipital neuralgia is typically described as a headache that radiates from the posterior portion of the head, forward around and above the ear in a “rams horn” distribution. When the greater or lesser occipital nerve is firmly palpated in patients with occipital neuralgia, pain will be replicated along this same distribution. Occipital neuralgia is becoming increasingly recognized as its own entity, or as an accompanying feature of other headache types. I believe this is likely due in part to some of the “cross talk” mechanisms between cervical afferents and the trigeminal nuclei. Occipital nerve blocks have been investigated as a treatment not only for isolated occipital neuralgia, but also for migraines with strong unilateral and posterior features.

Anecdotally, I have had a good deal of clinical success with occipital nerve blocks, not only in primary occipital neuralgia, but in other headache subtypes with an “occipital neuralgic” component (30). ❏ The view(s) expressed herein are those of the author and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force and Department of Defense or the U.S. Government.

MAJ Jason N. Harris, MD, practices neuro-opthalmology and general neurology at the San Antonio Military Medical Center.

He holds adjunct faculty appointments as an assistant professor of neurology at the Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, UT Health Science Center, San Antonio, Texas and Baylor University, Waco, Texas. He received a B.A. in zoology from Idaho State University and attended the Uniformed Services University of the Health Sciences, where he graduated AOA in 2006. In 2010, he completed a neurology residency at Walter Reed Army Medical Center.

He practiced general neurology at Tripler Army Medical Center, Honolulu, Hawaii, for three years and served in Afghanistan caring for patients with traumatic brain injuries. Dr. Harris completed a clinical fellowship in neuro-ophthalmology from The Wilmer Eye Institute at Johns Hopkins, Baltimore, Maryland, in 2014.

References 1. Headache Classification Committee of the International Headache Society (HIS).

The International Classification of Headache Disorders, 3rd edition (beta version).

Cephalalgia. 2013;33(9):629-808.

2. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 2013;154 Suppl 1:S44-53.

3. Dalkara T, Zervas NT, Moskowitz MA. From spreading depression to the trigeminovascular system.

Neurol Sci. 2006;27 Suppl 2:S86-90.

4. Goadsby PJ. The vascular theory of migraine—a great story wrecked by the facts. Brain.

2009;132(Pt 1):6-7.

5. Goadsby PJ. Pathophysiology of migraine. Ann Indian Acad Neurol. 2012;15(Suppl 1):S15-22.

6. Gupta R, Bhatia MS. A report of cranial autonomic symptoms in migraineurs. Cephalalgia.

2007;27(1):22-28.

7. Lambru G, Matharu MS. Trigeminal autonomic cephalalgias: A review of recent diagnostic, therapeutic and pathophysiological developments. Ann Indian Acad Neurol. 2012;15(Suppl 1):S51-61.

8. Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol. 2002;1(4):251-257.

9. Robertson BA, Morris ME. The role of cervical dysfunction in migraine: a systematic review.

Cephalalgia. 2008;28(5):474-483.

10. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain. 2013;154 Suppl 1:S44-53.

11. Kagan R, Kainz V, Burstein R, Noseda R. Hypothalamic and basal ganglia projections to the posterior thalamus: possible role in modulation of migraine headache and photophobia. Neuroscience.

2013;248:359-368.

12. Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache.

2006;46 Suppl 4:S182-191.

13. Burstein R. Deconstructing migraine headache into peripheral and central sensitization. Pain.

2001;89(2-3):107-110.

14. Bigal ME, Ferrari M, Silberstein SD, Lipton RB, Goadsby PJ. Migraine in the triptan era: lessons from epidemiology, pathophysiology, and clinical science. Headache. 2009;49 Suppl 1:S21-33.

15. Ward TN, Levin M. Diagnosis and pathophysiology of migraine. Expert Rev Neurother.

2004;4(3):383-390.

16. Woods RP, Iacoboni M, Mazziotta JC. Brief report: bilateral spreading cerebral hypoperfusion during spontaneous migraine headache. N Engl J Med. 1994;331(25):1689-1692 .

17. de Tommaso M, Sciruicchio V. Migraine and Central Sensitization: Clinical Features, Main Comorbidities and Therapeutic Perspectives. Curr Rheumatol Rev. 2016;12(2):113-126.

18. Ward TN. Migraine diagnosis and pathophysiology. Continuum. (Minneap Minn) 2012;18(4):753-63.

19. Sprenger T, Goadsby PJ. Migraine pathogenesis and state of pharmacological treatment options.

BMC Med. 2009;7:71.

20. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache.

2015;55(1):3-20.

21. Tfelt-Hansen PC. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2013;80(9):869-870.

22. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51(2):8997.

23. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society.

Neurology. 2012;78(17):1346-1353.

24. Frampton JE. OnabotulinumtoxinA (BOTOX(R)): a review of its use in the prophylaxis of headaches in adults with chronic migraine. Drugs. 2012;72(6):825-845.

25. Bendtsen L, Fernandez-de-la-Penas C. The role of muscles in tension-type headache. Curr Pain Headache Rep. 2011;15(6):451-458.

26. Bendtsen L. Drug and Nondrug Treatment in Tension-type Headache. Ther Adv Neurol Disord.

2009;2(3):155-161.

27. Friedman DI. The Eye and Headache. Continuum. (Minneap Minn) 2015;21(4 Headache):1109-1117.

28. Nager W, Munte TF, Marco-Pallares J, et al. Beta-oscillations in the posterior hypothalamus are associated with spontaneous cluster headache attack. J Neurol. 2010;257(10):1743-1744.

29. Ashkenazi A, Schwedt T. Cluster headache—acute and prophylactic therapy. Headache.

2011;51(2):272-286.

30. Ashkenazi A, Levin M. Greater occipital nerve block for migraine and other headaches: is it useful? Curr Pain Headache Rep. 2007;11(3):231-235.

Tools of the Trade

OPTP offers a wide variety of therapeutic tools for neck pain. The Treat Your Own Neck ™ book by Robin McKenzie provides neck relief exercises, while the Original McKenzie® Cervical Roll™ promotes natural sleeping habits. You can also help your patients relieve neck tension and headache pain with products like our Occipital Float ™, CranioCradle®, and Adriaan Louw’s Your Headache Isn’t All in Your Head.

Shop the full product line at OPTP.com.

Occipital Float™

CranioCradle®

Your Headache Isn’t All In Your Head

800.367.7393 | OPTP.COM

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

17

New Developments in the Pharmacologic Treatment of Chronic Migraine: A Summary of Recent Clinical Trial Results

By Christine Rhodes, MS

Treatment of individual migraine episodes is important to prevent the progression to chronic migraine (CM), which is especially debilitating and imposes a greater burden on patients and society. Treatments for the prevention of episodic and chronic migraine are currently available, and emerging therapies are on the horizon to provide new options for targeted treatment that is effective and safe.

Increasing understanding of the mechanisms in the brain that lead to migraine highlights the importance of terminating individual migraine attacks and preventing the chronification of migraine.

With increasing frequency of migraine attacks, prolonged activation of the neuronal networks involved in pain processing may lower the threshold for subsequent attacks, leading to central sensitization (1), and hypersensitivity. Thus, poor treatment efficacy among individuals with episodic migraine, leading to longer periods of exposure to pain, might increase the risk of new onset chronic migraine (2).

There are three broad approaches to treating CM: lifestyle and trigger management, acute treatments, and preventive treatments. Lifestyle measures such as regulating the timing of meals and sleep may reduce the frequency of attacks, but pharmacologic treatment is usually necessary. Management of comorbid conditions, including depression, anxiety, and other pain syndromes, as well as managing medication overuse, will help maximize the efficacy of other migraine treatments (3). A multimodal treatment approach is superior to simple drug treatment, especially in patients with CM (4).

18

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

Pharmacological treatment of CM is based on prompt treatment of acute attacks and preventive treatment. Epidemiologic studies suggest that approximately 38% of migraineurs need preventive therapy, but only 3% to 13% currently use it (5). Preventive treatment should be considered when migraine attacks occur on four to five days per month in those with normal functioning, or two to three days per month in individuals whose migraines cause significant impairment or disability (5).

Several drugs are currently considered to have the best evidence for efficacy for migraine prevention, including the beta blockers propranolol, timolol, and metoprolol; the antiepileptics divalproex sodium, valproate, and topiramate; and the triptan frovatriptan for menstrually related migraine (6). OnabotulinumtoxinA is the only agent specifically indicated for the prevention of chronic migraine and is effective and extremely well tolerated.

An extended release formulation of topiramate, Trokendi XRÂŽ, was FDA-approved for migraine prevention in April (7).

Until now, most migraine treatments, whether acute or preventive, have been nonspecific and their efficacy, safety, and tolerability often unsatisfactory. Therapies that target specific neural mechanisms, particularly calcitonin gene-related peptide (CGRP), are promising and may represent a turning point for migraine prevention, just as triptans revolutionized acute migraine treatment (8). CGRP, a neuropeptide that is released from trigeminal nerve endings, causes inflammation and vasodilation, and it spikes in the brain during migraine attacks. Monoclonal antibodies that bind to CGRP at the trigeminal nerve endings are thought to relieve migraine pain by circumventing afferent sensory transmission and subsequent development of central sensitization.

NEW DRUGS ON THE HORIZON Recently, Phase III clinical trial results were announced for three monoclonal antibodies targeting the CGRP ligand (eptinezumab, galcanezumab, and fremanezumab) and one targeting the CGRP receptor (erenumab). All four drugs show good safety and tolerability profiles and efficacy in migraine prevention, especially in high-frequency episodic and chronic migraine.

Makers of eptinezumab, a formulation for intravenous use, announced that the drug met its Phase III primary and key secondary endpoints in the PROMISE 1 trial, which evaluated the change in frequency of episodic migraine days after 12 weeks of intravenous administration of eptinezumab (9). From a baseline average of 8.6 monthly migraine days, patients taking the 300mg dose experienced 4.3 monthly migraine days and those taking 100 mg experienced 3.9 monthly migraine days, compared to 3.2 days for placebo. Secondary endpoints demonstrated responses that were improved from weeks 13 to 24, including a â&#x2030;Ľ 75% reduction in monthly migraine days for the 300 mg dose, 33.5% reduction for the 100 mg dose, and 24.8% for placebo.

The observed safety profile was similar to placebo. PROMISE 2 is evaluating the change in frequency of chronic migraine days

after 12 weeks, and topline results are expected in the first half of 2018.

Galcanezumab met its primary endpoints in three Phase III studies (EVOLVE-1, EVOLVE-2, and REGAIN), demonstrating statistically significant reductions in the number of monthly migraine headache days at both studied doses compared to placebo (10).

In EVOLVE-1, patients with episodic migraine had an average reduction of 4.7 headache days taking the 120 mg dose and 4.6 days taking the 240 mg dose, compared to an average reduction of 2.8 days for placebo over the six-month treatment period. In EVOLVE-2, those taking 120 mg experienced an average reduction of 4.3 headache days and those taking 240 mg experienced an average reduction of 4.2 days, compared to an average reduction of 2.3 days for placebo.

In the REGAIN trial, patients with chronic migraine treated with galcanezumab experienced an average reduction of 4.8 days with the 120 mg dose and 4.6 days with the 240 mg dose, as compared to an average reduction of 2.7 days for placebo. In all three trials, patients experienced statistically significant improvements compared to placebo in response rates and measures of daily activities. The most commonly reported adverse events were injection site reactions, including pain, and the observed safety and tolerability profile was consistent with findings from previous studies of galcanezumab. Submission of a Biologics License Application (BLA) to the FDA is expected in the second half of 2017.

Fremanezumab was evaluated in the HALO clinical trial program, and Phase III results were recently announced. In HALOCM, 1,130 patients with chronic migraine were randomly assigned to monthly or quarterly dosing of fremanezumab or placebo (11).

In the monthly dosing patients, a reduction of 4.6 headache days occurred; in the quarterly dosing patients, the reduction in headache days was 4.3 days, and for the placebo-treated group, the reduction was 2.5 days. In addition, there were significantly greater reductions in headache days during the first four weeks for the combined fremanezumab group than for the placebo group.

In HALO-EM, 256 patients with episodic migraine were randomly assigned to receive three monthly doses of 225 mg, one quarterly dose of 675 mg, or placebo (12). At baseline, patients had an average of 9.1 monthly migraine days, which was reduced by 3.7 days for the monthly dosing group and by 3.4 days for the quarterly group, vs. 2.2 days for the placebo group.

In addition, the number of days with disability was reduced by 64.7% for the treatment group and medication consumption was decreased by 39.0%. Further reductions in monthly migraine days also occurred in those already taking a migraine prophylactic compared with placebo (-4 vs -2 for the monthly dose group, and -3.7 for the quarterly dose group). Injection site pain was the most commonly reported adverse event. A BLA submission is expected later this year.

Erenumab, a once-monthly subcutaneous formulation, has completed Phase III evaluation, and its manufacturer submitted a BLA to the FDA in May. Results of two pivotal trials show a benefit in preventing episodic migraine, especially for the higher dose tested over an extended period (13). The first Phase III study, ARISE, studied 577 patients and compared erenumab 70 mg with placebo. Results demonstrated a statistically significant reduction of 2.9 days in the treatment group vs. 1.8 days in the

placebo group in monthly migraine days after nine to 12 weeks of treatment. In this trial, 39.7% vs. 29.5% of patients experienced a 50% or greater reduction in monthly migraine days and had a reduction of 1.2 vs. 0.6 in acute migraine-specific medication days.

In the second Phase III study, STRIVE, 955 patients were randomly assigned to receive erenumab 70 mg, erenumab 140 mg, or placebo for 24 weeks of treatment. The 70 mg group had a 3.2 reduction and the 140 mg group a 3.7 day reduction in monthly migraine days vs. a 1.8 day reduction for the placebo group. In addition, 43.3% and 50% of the active treatment groups vs. 27% of the placebo group had a reduction of 50% or greater in monthly migraine days. There were 1.1, 1.6, and 0.2 reductions in days for the use of migraine specific medications.

In this trial, patients receiving erenumab also has significant improvements in physical impairment and everyday activities scores. The safety profile of erenumab was similar to placebo across all treatment arms in the studies. The most common adverse events were upper respiratory tract infection, injection site pain, nausea, and nasopharyngitis.

While nonspecific treatments for the prevention of episodic and chronic migraine are currently available, new options for targeted treatment that is effective and safe are on the horizon, leading to better patient outcomes and reduced economic and quality-of-life burdens. ❏ Christine Rhodes has an MS in nutrition and is a medical writer based in New York City. Besides serving as clinical editor of The Pain Practitioner, she is a Certified Holistic Health Coach, American Association of Drugless Practitioners.

References 1. Bernstein C, Burstein R. Sensitization of the trigemino-vascular pathway: perspective and implications to migraine pathophysiology. J Clin Neurol. 2012;89:89-99.

2. Lipton RB, Fanning KM, Serrano D, Reed MI, Cady R, Buse DC. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine. Neurology. 2015;84:688-695.

3. Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015;6:115-123.

4. Diener HC, Solbach K, Holle D, Gaul C. Integrated care for chronic migraine patients: epidemiology, burden, diagnosis and treatment options. Clin Med. 2015;15:344-350.

5. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; The American Migraine Prevalence and Prevention Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349.

6. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.

7. Supernus receives final FDA approval for Trokendi XR® for migraine prophylaxis in adults and adolescents [press release]. Supernus Pharmaceuticals; Rockville, MD; April 5, 2017.

8. Giamberardino MA, Affatati G, Curto M, Negro A, Costantini R, Martelletti P. Anti-CGRP monoclonal antibodies in migraine: current perspectives. Intern Emerg Med. 2016;11(8):1045-1057.

9. Alder BioPharmaceuticals Announces Positive Eptinezuman Phase 3 Results for Prevention of Frequent Episodic Migraine [press release]. Bothell, WA: Alder: June 27, 2017.

10. Lilly Announces Positive Results for Three Phase 3 Studies of Galcanezumab for the Prevention of Episodic and Chronic Migraine [press release]. Indianapolis, IN: May 12, 2017.

11. Teva Announces Positive Results for Phase III Study of Fremanezumab for the Prevention of Chronic Migraine [press release]. Jerusalem, Israel: May 31, 2017.

12. Teva’s Fremanezuman Meets All Primary & Secondary Endpoints Across Both Monthly and Quarterly Dosing Regimens in Phase III Study in Episodic Migraine Prevention [press release].

Jerusalem, Israel: June 7, 2017.

13. Amgen Presents Erenumab Data at the 59th Annual Scientific Meeting of the American Headache Society [press release]. Thousand Oaks, CA: June 8, 2017.

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

19

The Power of Virtual Reality

By Christine Rhodes, MS

The Pain Practitioner interviewed Brenda K. Wiederhold, PhD, MBA, Chief Executive Officer of the Interactive Media Institute and President of the Virtual Reality Medical Center, which develops virtual reality (VR) environments and clinical protocols as well as conducting clinical research studies using VR and internet-based worlds.

CR: How did you get interested in virtual reality (VR) for chronic pain?

in the real world and having it reflected in the virtual world, is called augmented reality versus traditional virtual reality.

BW: I started using virtual reality to treat people with phobias and anxiety disorders, and then we started treating people who had presurgical anxiety or pain and anxiety during medical procedures. We were funded by the National Institute on Drug Abuse, National Institutes of Health, to create software and protocols to deal with procedural pain and anxiety for medical and dental procedures.

CR: How often does a patient undergo a virtual reality or an augmented reality treatment?

BW: We’re seeing about a 50% to 70% reduction in pain. Many people who have had chronic pain are able to quit taking medication, and others are able to reduce their medication dose. We’re starting to combine the virtual reality, cognitive behavioral therapy, and biofeedback with other medical devices, and we’re finding that the combination works even better than just virtual reality by itself or the device by itself.

After patients reported that it also helped their chronic pain conditions, we performed a small study at Balboa Naval Hospital in patients with migraine headaches, fibromyalgia, and back pain. We found that patients’ pain decreased when they distracted themselves with virtual reality during sessions, and, in addition, they were able to decrease their pain between sessions. For example, they learned that if they sit at home and focus on their pain, it will become worse. If they start doing some activities of daily living, some movement, something besides just sitting and focusing on their pain, the pain will go down. We also started using VR in our clinical practices both here and in Europe to treat patients with chronic pain.

CR: How long are the sessions?

BW: We find that 15- to 20-minute sessions are more effective.

The brain starts to remember those positive emotions, that feeling of being without pain. And, as we know, our brains are very plastic, so they start attaching to those new memories. We add exercises for the upper and lower extremities in the virtual reality so that patients start losing their fear of movement … New technology allows us to provide exercise programs at home, either online or for use with a VR device.

BW: We normally see patients once a week. Most people take 10 sessions.

CR: How would you rate their reduction in pain?

CR: Which types of pain conditions are particularly suitable for VR therapy?

BW: It works for shoulder pain, back pain, elbow pain, knee pain, migraine, fibromyalgia, complex regional pain. It has worked for every condition we’ve tried it, but we haven’t tried it on everything. We haven’t done a lot with diabetic neuropathy or neck pain.

CR: Is VR covered by insurance?

BW: We add VR as part of a traditional psychotherapy session.

We’re monitoring patients’ vital signs and teaching them to control their physiology with biofeedback, which is all part of the psychotherapy session. PPOs and some HMOs have covered psychotherapy. If insurance doesn’t cover mental health services, then they would not, of course, cover this either.

CR: Are the exercise sessions conducted while the patient wears the virtual reality device?

CR: How do you think VR will advance in the future?

BW: No, we found using a big screen is better because the head mount inhibits movement. Patients see their hands, their arms, their legs on the screen and, at the same time, see them in the real world. It’s very powerful. Seeing your body

BW: The exciting thing is that it’s starting to become more popular, more accepted by psychologists and the medical community. The cost has come down, and the usability has gone up with the recent technologies. When we started using this in 1996 for phobias and then pain conditions in

20

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

the early 2000s, VR was expensive and the equipment was temperamental. But it’s much easier to use, and the cost is not prohibitive, even for the individual therapist or physician, so I think we’ll start seeing it more widely disseminated and used.

We hold clinician training courses that are American Psychological Association (APA) accredited, we hold a conference every year, we hold specialized workshops, and I send out several publications, for both patients and for clinicians. I tell patients that there are treatments available that may provide a nice addition to their treatment protocol.

It won’t take the place of medicine, necessarily, but it may help to reduce their meds or it may help them start thinking differently. I have a gentleman who has had five shoulder surgeries and two traumatic brain injuries; he was in a very high-risk occupation. He knows he will probably always have some pain, but he doesn’t want to stay in a completely medicated state for the rest of his life, so he controls some of that pain with these technologies.

CR: Could a patient have an at-home VR set that they could use? Or is this only done in the office?

BW: Right now, I send it home with my patients, but we don’t have it completely available for the consumer yet. We hope to do that within the next six months.

CR: Does VR actually rewire the brain?

BW: Yes. We know that when someone has chronic pain, the

Corporate Council Members Support and Advance AIPM’s Mission

brain starts changing and adapting. The brain looks very different in a person with chronic pain than it does in someone not in chronic pain.

CR: Have imaging studies been done to document these changes?

BW: Yes, there have been some fMRI studies. Right now we’re working on a study with an implantable device. And we’re going to be using virtual reality enhanced cognitive behavioral therapy in addition to a naltrexone implant to help with the opioid crisis. The combination will help with addiction as well as pain management.

CR: I think if I were introduced to a virtual reality landscape and my pain was relieved, I wouldn’t want to leave!

BW: A lot of people say that. They ask if they will become addicted or prefer to be in the virtual world. In my 21 years of using VR that has not happened, even with the realistic worlds. It’s very empowering to go into that world, to escape that pain, to go into another dimension, and then to translate the new skill set and positive emotions in the realworld setting.

CR: What kind of skills? Slowing down their breathing and heart rate?

BW: That, as well as starting to understand that when they distracted themselves in the virtual world their pain level was a 1 out of 10 instead of 8 out of 10.

Our current Corporate Council members are:

The Academy of Integrative Pain Management values its relationships with commercial sponsors who support our goals and mission in a variety of ways. Many benefits are offered to Corporate Council members including premium advertising and visibility opportunities, complimentary company representative memberships, recognition on our website, networking with executives and members, and more.

For information on Corporate Council Membership, please contact Whitney O’Donnell Manager, Member Services, Academy of Integrative Pain Management, P: (209) 533-9744 ext. 117, E: wodonnell@integrativepain.org

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

21

CR: Who designs the virtual reality world?

BW: We’ve developed everything in-house. Patients work with the clinician, the graphic artist, and the computer scientist or the programmer. We work in a team to make sure we’re designing what patients need.

CR: So it really is individualized?

BW: It is, and we’ve found that you don’t have to have a 100% realistic virtual world, it just must have the proper cues. For instance, when we developed a world for patients undergoing chemotherapy after breast cancer, we used very soothing music, we had them walking very slowly so they didn’t get nauseous or cybersick. We used muted colors, nothing sharp or loud, music-wise or color-wise. We wanted everything with a soft touch.

they needed the curbs formed differently. They needed the hands shaped differently and larger. If we haven’t been to Iraq or Afghanistan we wouldn’t think those cues were important, but they are.

CR: Is their goal to have greater control over their surroundings?

BW: No, they need to go back into those surroundings and bring together all the fragmented memories they often have in post-traumatic stress and consolidate those memories, process those emotions, and then move through those memories.

VR is becoming more affordable, it is supported by studies proving it’s a useful adjunct. Many people have heard about it now and we have a more active consumer, a more active patient. The internet has allowed people to become much more educated about what is going on in the world as well as with their disorder. The power of the technology is translating technology and treatment into the home setting and letting patients help themselves in the future. As soon as we are able to get these into the hands of patients themselves, they’re going to be able to start self-treating in addition to coming in to their appointments.❏

CR: What would someone coming back from war with PTSD need?

BW: It varies. We’ve created 12 worlds for PTSD with the people coming back from Iraq and Afghanistan. One is a hospital for people that were combat medics or doctors or nurses.

Another is a convoy, and it has IEDs [improvised explosive devices] on the roadside so they’re able to see those and react to them. Another is a crowded marketplace. In another, they are walking through the streets and on patrol.

In some cases, we found that we had the cues wrong. So

5 REASONS To Apply for AIPM’s Advanced Pain Management Practitioner (APMP) Certificate Program–Prescriber Edition ➊ Document your extensive experience, knowledge and use of best practices in pain care. ➋ The only pain management certificate program that includes education specially developed to guide you through your studies. ➌ Show your patients, peers, and employers, you’ve gone above and beyond to provide safe and effective pharmacologic pain care. ➍ Gain visibility in AIPM’s online directory as an APMP certificate-holder. ➎ Conveniently schedule your exam when and where you want it.

NOW SIMPLER AND MORE AFFORDABLE THAN EVER! The application, review course, and examination are all included in a single registration fee. To learn more, http://www.integrativepainmanagement.org/page/apmp.

22

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

Integrative Management of Sensitized Chronic Pain with Ambulatory Autonomic Self-Regulation

By JP Ginsberg, PhD

Integrative health and medicine focuses on the whole person and makes use of all appropriate therapeutic approaches informed by evidence. Integrative health care is inherently inter-professional, and medicine is but one of several sections of total health care. The integrative management framework depends on diagnosis, treatment, and prevention of disease by allied health professionals including pharmacists, psychologists, speech pathologists, dietitians, occupational and physical therapists, to name a few. This approach puts patient health—and not just simply medical treatment—at the center of focus. Integrative management means that the relationship between practitioner and patient is central to achieving an outcome of improved health and wellness, and is often referred to as “empowering the patient.”

Chronic nociceptive pain is due to long-lasting tissue damage continually stimulating nerve fibers. Sensitized chronic nociceptive pain syndromes are characterized by the dysregulation of the autonomic nervous system (ANS). Normal ANS function reflects an adaptive level of interplay between the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS).

The PNS produces cardiac deceleration (“rest and digest”) and the SNS produces cardiac acceleration (“fight or flight” and the stress response). Stress develops from continual pain because of hyperarousal of the SNS, a process known as “HPA overdrive” because of the involvement of the hypothalamic-pituitary-adrenal

axis. HPA overdrive causes excess glucocorticoid signaling, receptor downregulation, an end to normal negative feedback regulation of the stress response, inhibition of descending cortical pain modulation (“nociceptive braking”), and proliferation of peripheral pro-inflammatory cytokines by catecholamines.

What does all this mean? It means heightened pain and increased stress responses become a self-reinforcing cycle, the pain threshold is lowered, and a neuromodulator picture develops that is equivalent to depression.

In addition to chronic nociceptive nerve signals that originate in tissue lesions, psychological catastrophizing and unremitting fear rumination further augment the prolonged stress response and are core aspects of pain sensitization. The list of chronic pain conditions that can become sensitized is quite large, including abdominal pain, fibromyalgia, phantom pain, headache, irritable bowel syndrome, and back pain, to name just a few. Sensitized chronic nociceptive pain can be reduced by autonomic self-regulation (ASR) because ASR dampens HPA hyperarousal, calms the SNS, stimulates robust PNS activity, and restores normal ANS function. ASR further empowers patients to overcome the psychological sources of stress that accompany chronic nociceptive pain and self-regulate their emotions.

ASR is defined as the technique of heart rate variability biofeedback (HRVB) that incorporates 1.) paced resonant frequency breathing (RFB), 2.) focused attention or mindfulness, and 3.) positive emotional cognitions such as acceptance, compassion, gratitude, prayer, and love. ASR can rehabilitate the ANS that has been deranged by sensitized chronic nociceptive pain.

Although HRV can be quite simply defined as variation in the time interval between heartbeats recorded either from the ECG or a plethysmographic (pulse) sensor, this simple definition belies the complexity that exists in both the quantitative analysis of inter-beat interval (IBI) data and the fundamental systemic physiological processes that underlie HRV. Healthy HRV contains a regular pattern of increasing and decreasing IBIs between consecutive beats that increases HRV, while unhealthy HRV is relatively low due to either little variation between IBIs or random, unorganized differences between consecutive beats. In the late 1970s, low HRV was found to be a powerful clinical predictor of mortality after myocardial infarction (1,2). By the late1980s, research revealed that good cognitive performance was related to high HRV (3) and certain forms of mental disorder were related to low HRV (4).

BIOFEEDBACK

Biofeedback in general is simply defined as the process of gaining greater awareness of physiological functions using instruments that provide information on the activity of those same systems, with the goal of being able to control them volitionally.

In addition to HR, physiological processes that can be controlled with biofeedback include brainwaves, muscle tone, and skin conductance. Clinically accurate measurement of IBI dates back to the beginning of the of the 20th century, but it was the electronic digitization of computer software, simplifying the quantitative analysis of HR and calculation of HRV, that accounts for the proliferation of interest in HRV.

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

23

Biofeedback has its roots in the early 1970s. HRVB was pioneered by Doc Lew Childre, Jr. Childre founded the HeartMath® Institute in 1991 and developed the concept of “heart-braincoherence” as an HRV waveform pattern reflecting emotional states (5). Childre promoted his “Heart Zones” music and HRV biofeedback as ways to ameliorate stress and negative emotions.

While breath or breathing training is an ancient practice with numerous forms, production of HRV coherence depends critically on RFB with paced breathing around six breaths per minute. The response of the ANS to RFB increases the amplitude of HRV rhythmic variation because six cycles/minute (10 seconds/cycle = 0.1 cycle/second = 0.1 HZ) is the resonant frequency of the entire cardiovascular system (respiration, heart rate, baroreflex, and vasomotor tone) and parasympathetic outflow peaks.

Today, HRVB is widely and popularly taught and learned globally. Continual improvements in software algorithms and hardware have produced tools that are more efficient, more sensitive, more adaptable, more meaningful, and better visualized for collection and analysis of HRV data.

While HRV monitoring and HRVB in the past has been done as a static “snapshot” of HRV status with sensors cabled to a desktop or laptop computer, the future is ambulatory, real-time, and dynamic in naturalistic settings. Development of different platforms is being solicited by small business development grants by the Department of Defense and National Science Foundation, in the private entrepreneur market, and university research to create wearable systems that are effective for reliable measurement of IBI in naturalistic and battlefield environments. But many issues remain to be resolved before this movement moves fully into clinical practice and has utility for clinical pain management; not all devices have bridged from research quality to FDA approval; questions of privacy, confidentiality, and HIPAA rules for HRV data are being confronted; and third-party reimbursement is poor.

HRV TECHNOLOGIES

Fitness watches continuously track HR and can transfer data to a software dashboard that can compute HRV. Recent clinical research with an Apple Watch app tracked people with epilepsy and found that seizures are often related to stress and missed sleep.

Small chest patches with electrodes contain highly miniaturized fully featured circuits for ECG detection. Vests are available that have HR electrode sensors and include additional sensors such as 3-axis accelerometers, and they measure respiration, skin conductance, and even more sophisticated physiological measures such as skin and ambient temperatures, “pulse-transit-time” (an indirect measure of systolic blood pressure), and EMG. Ambulatory HRV monitoring has become a player in the health informatics “big data” movement. What is envisioned is having wireless transmission of HR data through processing algorithms in the cloud or through separate servers. The large-scale application of this plan falls into data mining protocols, from which new and important insights about basic HRV properties can be extracted.

On the individual level, transmitted HR data can be analyzed for comparability with normal healthy and with known physical and mental clinical populations. The “trainable adaptive focused replicator network for analyzing data” was patented by Wasyl Malyj, PhD, to classify patterns using array elements that “learn” to replicate predetermined subgroups. This advanced wireless signal processor inputs physiological measures through large scale da-

tabases and Dr. Malyj’s patented FFT/neural network and pattern recognition algorithm. The result is fast matching of patient data to provide 1.) predictive warning of acute health crises and 2.) real time evaluation of diagnostic and treatment options for complex patient needs, using matched clinical records from other, similar cases. This is the bridge to individualized medical care plus a way to fill gaps in patient-doctor communication.

Surely, the most futuristic method of HR monitoring, now a reality, is remote real-time detection of pulse. Researchers have successfully deployed several systems that can successfully measure pulse at a distance with as much accuracy as ECG: radar embedded in a smartphone camera programmed to display pulses as micro-movements invisible to the eye; video processing algorithm magnifying subtle changes in color reflecting pulse pressure skin redness; microwave Doppler radar. The sciencefictional “Star Trek” medical tricorder for whole body scanning is no longer fictional!

We now can apply new HRV technologies and algorithms in a dynamic way for a modest cost to yield powerful gains in research and delivery of individualized health. How can the use of technologies for ambulatory ASR contribute to individually empowered integrative management of sensitized chronic nociceptive pain? Personalized and real-time dynamic assessment of HRV status gives us feedback about when we are functioning naturalistically within normal parameters, as well as early and immediate detection of potentially adverse changes in health status. These technologies are a tool we can use to raise our selfawareness and thereby help us perceive and manage the stresses of life, thereby reducing the physiological overload that produces sensitized, heightened pain and breaking the pain, stress, and depression cycle. With ambulatory self-monitoring, reliance on medical services and utilization of health care resources can decrease, lowering costs with fewer side effects. The bottom line is better health and quality of life and more efficient allocation of expensive health care procedures.❏ JP Ginsberg, PhD, is a licensed clinical psychologist and neuropsychologist at the Dorn VA Medical Center, Columbia, South Carolina, where he is an advocate for integrative health and wellness using mind-body treatments for pain and PTSD. References 1. Wolf M, Varigos G, Hunt D, Sloman J. Sinus arrhythmia in acute myocardial infarction. Med J Aust.

1978;2:52-53.

2. Kleiger RE, Miller JP, Bigger JT, Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59:256-262.

3. Kammel H, Haase H. The visual stress model—a psycho-physiological method for the evaluation of operational reliability of pilots and cosmonauts. Acta Astronaut. 1987;15:125-132.

4. Chernigovskaya N, Vaschillo E, Petrash V, Rusanovsky V. Voluntary regulation of the heart contraction rate as a method for correcting the functional status of neurosis patients. Fiziol Cheloveka. 1990;16:58-64.

5. McCraty R, Atkinson M, Tiller WA, Rein G, Watkins AD. The effects of emotions on short-term power spectrum analysis of heart rate variability. Am J Cardiol. 1995;76:1089-1093.

Want to know more?

Join Dr. Ginsberg and his colleagues for a 6-hour workshop at the 28th Annual Meeting in San Diego.

24

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

Behavioral Interventions for Pain Embrace Technology, Broader Integration into Health Care Systems

By Debra Nelson-Hogan

Beth D. Darnall, PhD, is clinical associate professor in the department of anesthesiology, perioperative and pain Medicine at Stanford University.

Her NIH-funded research investigates mechanisms of pain catastrophizing, cognitive behavioral therapy (CBT), and the effectiveness of a targeted treatment she developed. She also studies prevention of post-surgical pain and outpatient opioid tapering.

Dr. Darnall is passionate about working with people who suffer chronic pain and is developing novel interventions that target some of the psychosocial factors that we know are predictive for the experience of pain, and for pain treatment outcomes.

One of the key factors is catastrophizing. “I developed an online intervention that specifically targets pain catastrophizing. We are investigating whether we can use this to treat people before they have surgery or an invasive procedure as a way to potentially improve post-surgical healing and recovery, and help prevent some chronic post-surgical pain,” she says.

She notes that some of the most predictive factors for postsurgical outcomes are pre-surgical psychological factors that relate to pain. “Catastrophizing is one of the major factors that contributes to pain intensity, suffering from pain, and it predicts response to pain treatments,” says Dr. Darnall. “I developed a two-hour targeted class to address pain catastrophizing in our patients at the Stanford Pain Management Center.” Dr. Darnall presented the single-session class to large groups of chronic pain patients, between 35 to 80 at a time.

She adds, “I invite patients to bring family members or friends because pain isn’t an isolated issue and knowledge allows them to offer stronger support. We need to get out of this mindset of treating the patient in isolation. We need to expand our treatments, our scope beyond the patient, and be thinking more about systems and families.”

Her group’s pilot work showed that the targeted, single-session pain psychology class was effective for reducing pain catastrophizing. Now, with NIH funding, she and co-PI Sean Mackey, MD, PhD, are examining the longer-term effects of the class, and they are characterizing who benefits most from this brief treatment, and who may need extended treatment.

Because pain catastrophizing is one of the most potent predictors for post-surgical pain, including the development of chronic post-surgical pain, Dr. Darnall’s next step was to adapt her two-hour targeted class for pre-surgical patients, making it a fully online program called, “My Surgical Success.” “Chronic postsurgical pain affects about 10% of people who undergo surgery each year; and for some surgeries that rate is as high as 35%,”

26

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

she says. “With 230 million surgeries performed each year, we are talking about a significant number of people.”

Participants go to the My Surgical Success website, download forms, and then watch a 90-minute educational video. They do the program in the comfort of their own homes and for free.

She says the patients essentially create their own personalized plan before surgery to better manage pre-surgical psychological distress. They also use it post surgically to address any pain or emotional distress that they’re having.

This leads to the idea of psychological treatment for pain and self-management, which Dr. Darnall describes as “critical,” yet underappreciated components of pain care. “These treatment approaches equip people living with pain with the information and the skills that will allow them to best self regulate their distress and their pain. We can greatly reduce suffering and even pain intensity when these treatments are utilized appropriately. It’s not something to be used intermittently, or once, but when it’s used in a dedicated way we see results.”

She continues, “We know that a similar model, learning all of those skills and tools that one can use to best regulate their pain intensity by learning to calm their own nervous system, gives patients the best results.”

Although there still are many barriers to accessing psychological behavioral treatment for pain, including the time it takes to come back for multiple sessions, insurance coverage, copays, travel, and the fact many people can’t find skilled clinicians in their area, in many ways it is a new era for behavioral health and its role in managing pain. In light of the “opioid crisis” and national and regulatory bodies calling for practitioners to employ more non-pharmacologic treatments to manage pain, Dr. Darnall says, “There is heightened interest in integrating behavioral medicine and pain psychology treatment programs into existing health care systems, that previously did not have these services available.”

How does she think the pain management field will change to meet an increasing need for treatment? “I believe that in the future, we’re going to see more reliance on online treatments using technology to develop and disseminate affordable treatments that dismantle or at least address many of the existing barriers that prevent people with chronic pain from having the comprehensive care that they truly need to move forward with their lives and reduce their own suffering.”

She believes that it is incumbent upon health care systems and practitioners to find ways to connect people living with pain to accessible treatments. “We have to think beyond traditional systems that involve insurance, for instance, because we have always had difficulty accessing good psychological care for chronic pain,” Dr. Darnall says.

Dr. Darnall’s professional relationship with pain management began during a clinical internship at the Tucson VA. “If you are a psychologist in the VA, you’re dealing with pain—it is so prevalent

in mental health. I loved it and discovered that I was comfortable in the context of suffering—I was not afraid of it—and naturally could work with individuals who were suffering. That inspired me to do a postdoctoral fellowship at Johns Hopkins University where I was treating individuals with catastrophic burn, amputation, spinal cord injury, and major surgeries. The central theme was pain and also pain and loss. Often they go hand in hand,” she says.

She learned this from her own experience with unexplained pain when she was 19. “I freely admit to having been a very effective pain catastrophizer, so I understand that construct very well. I tell patients in my classes that I have experience in pain. I’ve been treating pain for 15 years. I have national funding. But truly my best experience is having been a patient with pain for whom there were no real answers from the medical system.”

It didn’t go well for her. “I ended up in the ER at one point, my pain was so severe, and I just wanted to know what was wrong with me. I was 19, I was scared, I was away at college, and I had just lost someone who was dear to me; of course my pain worsened. At the hospital they did a medical workup, and they didn’t have any answers. No one knew what was wrong with me, but they sent me home with a bottle of Vicodin. That was the answer 25 years ago in 1992, and yet, so little has changed it could have been last year,” Dr. Darnall says.

She believes we need to increase the speed at which research results are delivered.

“Traditionally, it took approximately 17 years from when you start researching something until you publish the results, disseminate the information, and for that treatment to get integrated broadly into clinical practice. In comparison, we published our paper on the

single-session pain psychology class in 2014, and within the year I had clinicians and health care systems knocking on my door asking for it. This faster speed is exciting for the field of pain; new solutions are needed to meet the tremendous need for treatments that reduce suffering.”

When asked what she would like to see happen in the pain space in the next five years, Dr. Darnall says, “I am hoping for more creative models that integrate technology, whether that’s online interventions, greater use of social media, apps, or technologies such as virtual reality. I really believe that integrating technology into our treatment approaches is part of the future. In doing so, ideally it would help leverage us out of this conundrum where national policies and payer systems obstruct access to the treatments that we know work best. These are safe, evidence-based treatments, and our patients are having difficulty accessing them,” she says. “Within five years, my ‘pie in the sky’ wish is that the government will stand up and better support evidence-based, effective, safe pain treatment for the millions of Americans who need it. That will require support in the form of policy change and payer systems coverage.”

While policy changes may be off in the future, already she sees positive changes afoot. Increasingly, she is being asked to develop pain psychology treatment pathways for health care systems—in part to specifically provide non-opioid strategies. “Helping health care systems transform and integrate the biopsychosocial treatment approach is just wildly exciting to me. I see it as an indication that the consciousness of health care is transforming in an incredibly positive way,” she says. ❏

Research Recently published case series study in the Journal of Clinical Anesthesia.

Title: A novel treatment for chronic opioid use after surgery

A new non-invasive, alternative pain treatment for both acute and chronic pain. The Phoenix Thera-Lase System is a Class IV laser therapy modality that is transforming treatment, and providing positive patient outcomes.

Contact Us: 469-567-3959

www.phoenixthera-lase.com

Jay Glazer – Fox Sports, Unbreakable Performance

“It is a game changer at Unbreakable for inflammation and scar tissue… best thing I’ve ever used”

“I played for the Dallas Cowboys for 14 years and I’ve gone through a lot of physical therapy but nothing like the Phoenix Thera-Lase” Randy White – Dallas Cowboys DT, HOF 94

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

27

What is Photobiomodulation?

A brief review of therapeutic lasers

By Ernesto Cesar Pinto Leal-Junior, PhD, and Douglas Johnson, ATC

Light has a very powerful influence on the body, stimulating some biological processes while inhibiting others. Photobiomodulation (PBM) therapy, also known as low-level laser therapy (LLLT), continues to be widely used for injury management and pain relief.

Its popularity as one of the most exciting and novel innovations in physical therapy and chiropractic has expanded its use to prophylactic care as well as the improvement of sports performance by athletes. The therapeutic stimulation from a laser relaxes muscles, increases local blood circulation, and relieves pain from a variety of soft tissue injuries. While an impressive body of evidence to categorically support PBM exists, clinicians often lack the basic understanding of PBM and how to best determine which devices are best.

The use of sales hype and the opinions of self-appointed experts in the field have let users pay a high price for something that they do not need or may not be as beneficial as promised.

This type of marketing stretches the truth to highlight the “potential” benefits of these devices while failing to mention the drawbacks—and lack of scientific validation.

More than 15 years after its discovery, research has continued to uncover the basic mechanisms of action of PBM, and the growing list of evidence supports its use in many conditions. Due to the wide array of device parameters (wavelength, power, pulse parameters), research with a specific device is like a key, in that it is specific to that device. The specific parameters in a tested device do not always translate into an “equal” success—or failure—with a device with very different technical characteristics.

First, there are low-level therapeutic lasers, where the generation and delivery of photons (particles of light) create positive biochemical reactions. “Continuous wave,” or CW, refers to a laser that produces a continuous output beam, sometimes referred to as “freerunning.” The second type, high-powered lasers, includes all Class IV lasers, which were originally designed as surgical instruments.

As the power output increases, the light and the corresponding heat increases. The thermal limit can vary from patient to patient and is also dependent on the wavelength of the laser.

SELECTING A LASER DEVICE Currently there are several different types of lasers available to clinicians. Selecting the right device not only dictates understanding the mechanism of how light from that device interacts with the biological target, but the diverse set of parameters necessary to produce the therapeutic effects.

Ultimately, devices should be compared on the physiological effect on the tissue, whether the response is photochemical, photophysical, or photothermal. Devices with high power and low penetrative effect will produce greater photothermal effects at the expense of the therapeutic benefit. Similarly, a device that is under powered with a greater depth of penetration would also lack a good clinical effect since it would not have enough energy to trigger the biological response.

28

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

Supporters of high-powered devices claim that Class IV lasers penetrate tissue better than low-powered devices. Lee and Youn (1) demonstrated that the amount of light that passes through the skin is wavelength dependent and the 830 nm laser will penetrate farther into the body than 655 nm, 980 nm, or 1064 nm lasers. Hudson, et al., (2) found that a low-level laser with 808 nm penetrates as much as 54% deeper than 980 nm light from a high-powered laser.

While a high-powered laser can deliver hundreds of joules in a very short time, the downside is that it results in an unintentionally high dose. This results in less than predictable outcomes and, more importantly, an unwelcome effect of heat. Simply put,

penetrating the skin barrier cannot be compensated by a higher power output, as the additional light will be absorbed superficially, more quickly, leading to greater heat generation (3). The FDA laser classification refers only to a potential hazard to the retina and is not relevant to the laser’s efficacy.

POWER, PENETRATION, AND PULSING Does increased power mean increased depth of penetration?

No, this is a common misconception. Power has little to do with depth of penetration. Instead, it directly affects the concentration of photons at targeted tissue. Depth of penetration is an often debated subject, but it is agreed that this is dependent on wavelength or “color” and method of delivery.

Clinicians should take caution when using these high-powered lasers to avoid situations where heat may not be indicated including wounds, acute injuries, and areas of paresthesia. The risks of possible tissue overheating, retinal damage, or increases in discomfort outweigh the novelty of using a higher-powered device.

Since PBM therapy remains a non-thermal modality and does not rely on surface heat to be efficacious, a newer category of the therapeutic lasers is being explored. Super-pulsed laser is also classified as a low-level power device, but the light is delivered differently than with CW and high-powered devices. Superpulsed lasers (SPL) produce “bursts” of energy at a higher peak power, but the average power output is like that in low-level CW lasers. Tissues do not have the time to “transfer” the tremendous heat production over such a short period of time. The lower mean outputs of power output prevent the conversion of photons to heat (4).

Pulsing and super pulsing, by nature, have a clear distinctive advantage; their operation, by design, is to minimize heat. Superpulsed lasers create the desired higher peak power, however due to the ultrashort pulses, little resulting heat accumulates within the target tissue. Many light sources such as infrared emitting diodes (IREDs) and light emitting diodes (LEDs) are often mechanically pulsed to reduce photothermal effects within the tissue.

This resolves any issues with the thermal inefficiency of higherpowered devices, especially those with poor skin penetration due to improper wavelength selection.

It has been suggested in the literature that other modes, such as super pulsing, may have different skin penetration time profiles.

Super-pulsed GaAs lasers utilizing a 905 nm wavelength have been documented to have the ability to reach deep tissues. The lack of thermal overloading allows for the device to be held static over the treatment area without the need for continuous scanning.

There is compelling evidence to suggest that one of the basic mechanisms of PBM is the acceleration of electron transfer by electromagnetic radiation in the visible and near infrared region of the spectrum (5) via the modulation of cytochrome c-oxidase (CCO) activity. Single wavelength probes (both point and clusters) are limited by the specific absorption spectrum of that specific wavelength. Beneficial adenosine triphosphate (ATP) energy, nitric oxide (NO), and reactive oxygen species (ROS) have demonstrated biostimulatory effects from across a much broader range of wavelengths. It was suggested that a combination of wavelengths

may provide a more efficient means of triggering the phototherapeutic response. Rather than attempting to increase the activity of CCO with a single wavelength with higher power and just one set peak time activation, the use of additional wavelengths of lower powers will stimulate additional peak activation of the CCO. Clinicians should consider the intended use for the PBM device. Care should be taken when evaluating marketing materials that any supplied or noted studies are based upon that exact unit or model and not another “light” device. Be mindful that not all devices are equal, nor are all light devices therapeutic.

PBM has no known side effects and is only restricted during pregnancy or in the presence of cancer.

Scientific evidence for the use of low-level-laser devices continues to grow. PBM is non-invasive, has minimal to no side effects or contraindications, and is easy to administer to patients in clinically relevant treatment times. PBM should be considered for patients who present with muscle strains (6), tendinopathy (7), neck and low back pain (8), joint sprains, and soft tissue injuries. ❏ Ernesto Cesar Pinto Leal-Junior, PhD, is a professor at Nove Julho University in Sao Paulo, Brazil.

His area of research is phototherapy in skeletal muscle disorders and he has published more than 80 scientific papers, with more than 40 presented at national and international congresses.

Douglas Johnson is a certified athletic trainer with more than 20 years of clinical/industrial experience. He attended Wayne State University and the University of Detroit-Mercy where graduated summa cum laude with a bachelor of science degree in sports medicine. He is senior vice president, Clinical and Scientific Affairs, at Multi Radiance Medical, and he is involved in numerous laser research studies.

References 1. Lee S, Youn J. Evaluation of diffuse reflectance in multi-layered tissue for high intensity laser therapy. J Optical Soc Korea. 2013;17( 2):205-212.

2. Hudson DE, Hudson DO, Wininger JM, Richardson BD. Penetration of laser light at 808 and 980 nm in bovine tissue samples. Photomed Laser Surg. 2013 Apr;31(4):163-168.

3. Tunér, J. (2014). No cure from LiteCure. Ann Laser Ther Res. Annals Issue. 2014.

4. Hashmi JT, Huang YY, Sharma, SK, et al. Effect of pulsing in low-level light therapy. Lasers Surg Med. 2010. 42(6):450-466.

5. Karu T. The Science of Low-Power Laser Therapy. Amsterdam: The Netherlands: Gordon and Breach Science Publishers; 1998.

6. Gur A, Sarac AJ, Cevik R, Altindag O, Sarac S. Efficacy of 904 nm gallium arsenide low level laser therapy in the management of chronic myofascial pain in the neck: A double-blind and randomize-controlled trial. Lasers Surg Med. 2004;35(3)229-235.

7. Stergioulas A, Stergioula M, Aarskog R, Lopes-Martins RA, Bjordal JM. Effects of low-level laser therapy and eccentric exercises in the treatment of recreational athletes with chronic Achilles tendinopathy. Am J Sports Med. 2008;36(5):881-887.

8. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet. 2009;374(9705):1897-1908.

THE PAIN PRACTITIONER

| VOLUME 27, NUMBER 4 |

29

ADVERTISING DIRECTORY To Advertise Contact sales@integrativepain.org or 209-533-9744.

Depomed Nucynta ER www.nucynta.com 866-458-6389 COVER 2, PAGES 3-8 Micro Format, Inc. Secure Prescription Paper: Rx Pads, Laser Rx Paper, Thermal Rx Paper Rolls www.RxPaper.com, www.PrescriptionPaper.com 800-333-0549 PAGE 30 Transition Consultants Medical Practice Sales, Appraisal and Financing www.TransitionConsultants.com 800-416-2055 PAGE 30 Electromedical Products International, Inc Alpha-Stim www.alpha-stim.com 800-FOR-PAIN (367-7246) PAGE 31 OPTP Pain education and therapy products www.optp.com 800-367-7393 PAGE 17 Phoenix Thera-Lase Systems Alternative pain treatment for chronic opioid use http://www.phoenixthera-lase.com/ 469-567-3959 PAGE 27 Multi Radiance Medical www.multiradiance.com 1-800-373-0955 PAGE 25

PRACTICES WANTED: PAIN MANAGEMENT, PM&R, & PT Considering Selling your Practice? We are seeking practices on behalf of qualified buyers. Flexible deal structure, all-cash, with favorable terms. Option for sellers to remain post-sale as employed providers.

Contact: Mo Majdi 800-416-2055 http://TransitionConsultants.com

THE 28TH ANNUAL MEETING

The ONLY Clinical Meeting Dedicated to Integrative Pain Management

San Diego, California October 19-22, 2017 Hilton San Diego Bayfront Over 3+ days, you’ll earn up to 25 hours of CEU/CME – plus you will: • Learn about the newest, evidence-based, integrative approaches to pain management.

• Get best practices of team-based care for the most commonly encountered and challenging painful conditions.

Check out our special all-inclusive registration and hotel deals

at http://www.integrativepainmanagement.org/event/2017

30

| TH E PAI N P R AC TITIO N E R | J U LY / A U G U S T 2 0 1 7

• Participate in interactive discussions about case studies and lessons learned from other members of the pain care team and experts in the field.

• Be at the forefront of the biggest policy and advocacy issues affecting access and reimbursement for integrative pain care.

LET NOTHING STOP THEM.â&#x201E;¢

NONPROFIT ORG US POSTAGE PAID BURL VT 05401 PERMIT #19 8700 Monrovia Street, Suite 310, Lenexa, KS 66215

For the past 28 years, we have beenâ&#x20AC;&#x201D; and still areâ&#x20AC;&#x201D;the only national professional organization dedicated to advancing a multidisciplinary, team-based approach to pain management.

Show Your Commitment to Patient-Centered Care!

Become a Member of the Academy of Integrative Pain Management Today 1. Networking opportunities with other members of the pain care team, especially through our Shared Interest Groups (SIGs).

2. Free access to 70+ free and discounted CME courses in our online, on-demand Pain Care Learning Center.

3. Inclusion in our Find a Provider online member directory so that new patients can find you.

4. A complimentary print subscription to our award-winning magazine, The Pain Practitioner.

5. Free CV/resume postings and a searchable database of new job openings in our Career Center.

Plus, Discounted Group Membership Rates Are Now Available!

We value a team-based approach so much that we offer significant discounts when 3 or more individuals join from the same facility or clinic.

Join or Renew Your Membership Today!

Visit integrativepainmanagement.org or call (209) 533-9750.