PAINWeek Journal Vol 7, Q4 by PAINWeek

vol. 7 q 4 2019

the cracked mirror: exploring opioid abuse-deterrent methods from the laboratory to the real user p. 14 icebergs, oceans, and the experience of pain p.20 starting an acute pain service is harder than you think… omg! why did I agree to do this again? p.30 the force is with you: mind tricks for chronic pelvic pain p.36

Education moves forward. www.painweek.org

eXeCUTiVe eDiTOR KEViN L. ZACHAROFF md, facpe, facip, faap

eeK

PUBLiSHeR PAINW

ART DiReCTOR DARRYL FOSSA

eDiTORiAL DiReCTOR DeBRA WeiNeR eDiTOR HOLLY CASTeR

eDiTORiAL BOARD

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

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

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

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

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

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

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

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

Copyright © 2019, PAINWeek, a division of Tarsus Medical Group. The opinions stated in the enclosed printed materials are those of the authors and do not necessarily represent the opinions of PAINWeek or its publication staff. PAINWeek does not give guarantees or any other representation that the printed material contained herein is valid, reliable, or accurate. PAINWeek does not assume any responsibility for injury arising from any use or misuse of the printed materials contained herein. The printed materials contained herein are assumed to be from reliable sources, and there is no implication that they represent the only, or best, methodologies or procedures for the pain condition discussed. It is incumbent upon the reader to verify the accuracy of any diagnosis and drug dosage information contained herein, and to make modifications as new information arises. All rights are reserved by PAINWeek to accept, reject, or modify any advertisement submitted for publication. It is the policy of PAINWeek to not endorse products. Any advertising herein may not be construed as an endorsement, either expressed or implied, of a product or service.

The national conference on pain for frontline practitioners.

2020

SePTeMBeR 8â&#x20AC;&#x201D;12

Global Education Group (Global) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education to physicians. Global Education Group designates this live activity for a minimum of 39.0 AMA PRA Category 1 Credit(s)â&#x201E;˘. This activity will be approved for continuing pharmacy, psychology, nurse practitioner, nursing, and dentistry education. Applications for certification of social work NASW and family physician AAFP hours will be applied for. For more information and complete CME/CE accreditation details, visit our website at www.painweek.org.

vol. 7 q4 2019

key topic

the cracked mirror exploring opioid abuse-deterrent methods from the laboratory to the real user

by beatrice setnik

behavioral

icebergs, oceans, and the experience of pain

by becky curtis mel pohl

advanced practice provider

starting an acute pain service is harder than you think… omg! why did i agree to do this again?

by mechele fillman

pelvic pain

the force is with you: mind tricks for chronic pelvic pain

by jorge carrillo georgine lamvu

op-ed

spilled beans & hard stops how legislation, guidelines, and reimbursement policies impact patient care

by jessica geiger

back to basics

the basics of pain treatment (p1)

by kevin zacharoff

pw next generation

with alexis lapietra

58 59 60

clinical pearls

by doug gourlay

one-minute clinician

with kevin zacharoff, steve passik, mary lynn mcpherson, jeanette jacknin, colleen fitzgerald, sean mackey

62 65

pundit profile

with jeremy adler

puzzled?

by wendy caster

20 30 36 44

pain by numbers

PWJ | www.painweek.org

Q 4 | 2019

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

SYMPROIC® (naldemedine)

✓

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

✓

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

✓

Multiple routes of administration1-3

✓

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

✓

No impact on opioid-mediated analgesia1-3

✓

No significant pharmacokinetic drug-drug interactions3-5

✓

Comparison of products does not suggest comparable efficacy and safety or interchangeability. Please consult the full Prescribing Information for all products. MOVANTIK is a registered trademark of the AstraZeneca group of companies. SYMPROIC is a registered trademark of Shionogi & Co., Ltd. Osaka, Japan.

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

IMPORTANT SAFETY INFORMATION • RELISTOR tablets and injection are contraindicated in patients with known or suspected mechanical gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. • Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. • If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

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

IMPORTANT SAFETY INFORMATION (cont’d) • Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal. • Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. • The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. • A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment. • A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions and dose adjust per Prescribing Information as may be indicated. • In the clinical studies, the most common adverse reactions were: OIC in adult patients with chronic non-cancer pain • RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%). • RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%). OIC in adult patients with advanced illness • RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%), flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%). To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see Brief Summary of Prescribing Information on the following page. REFERENCES: 1. RELISTOR [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals. 2. Movantik [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP. 3. Symproic [prescribing information]. Raleigh, NC: BioDelivery Sciences International, Inc. 4. Michna E, Blonsky ER, Schulman S, et al. Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic nonmalignant pain: a randomized controlled study. J Pain. 2011;12(5):554-562. 5. Data on file. Clinical study report MNTX3201. Salix Pharmaceuticals; 2015. 6. Slatkin N, Thomas J, Lipman AG, et al. Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. J Support Oncol. 2009;7(1):39-46. 7. Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008;358(22):2332-2343. www.salix.com 400 Somerset Corporate Boulevard, Bridgewater, NJ 08807 Tel 800-321-4576 Relistor is a trademark of Salix Pharmaceuticals or its affiliates. ©2019 Salix Pharmaceuticals or its affiliates. REL.0201.USA.19

BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use RELISTOR safely and effectively. See full prescribing information for RELISTOR. RELISTOR (methylnaltrexone bromide) 150 mg tablets, for oral use. RELISTOR (methylnaltrexone bromide) injection, for subcutaneous use. 8 mg/0.4 mL methylnaltrexone bromide in single-dose pre-filled syringe. 12 mg/0.6 mL methylnaltrexone bromide in a single-dose pre-filled syringe, or single-dose vial. Initial U.S. Approval: 2008 INDICATIONS AND USAGE Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation. Opioid-Induced Constipation in Adult Patients with Advanced Illness or Pain Caused by Active Cancer RELISTOR injection is indicated for the treatment of OIC in adult patients with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care. CONTRAINDICATIONS RELISTOR tablets and injection are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation. WARNINGS AND PRECAUTIONS Gastrointestinal Perforation Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom. Severe or Persistent Diarrhea If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider. Opioid Withdrawal Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain The safety of RELISTOR tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 12-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR tablets 450 mg orally (200 patients) or placebo (201 patients). After 4 weeks of double-blind treatment administered once daily, patients continued 8 weeks of double-blind treatment on an as needed basis (but not more than once daily). The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR tablets are shown in Table 4. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal. Table 4: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Tablets in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 1) RELISTOR Tablets Placebo Adverse Reaction n = 200 n = 201 Abdominal Pain** 14% 10% Diarrhea 5% 2% Headache 4% 3% Abdominal Distention 4% 2% Vomiting 3% 2% Hyperhidrosis 3% 1% Anxiety 2% 1% Muscle Spasms 2% 1% Rhinorrhea 2% 1% Chills 2% 0%

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

The safety of RELISTOR injection was evaluated in a double-blind, placebocontrolled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 2) included a 4-week, doubleblind, placebo-controlled period in which adult patients were randomized to receive RELISTOR injection 12 mg subcutaneously once daily (150 patients) or placebo (162 patients). After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR injection 12 mg subcutaneously was administered less frequently than the recommended dosage regimen of 12 mg once daily. The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR injection are shown in Table 5. The adverse reactions in the table below may reflect symptoms of opioid withdrawal. Table 5: Adverse Reactions* in 4-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Injection in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 2) RELISTOR Injection Placebo Adverse Reaction n = 150 n = 162 Abdominal Pain** 21% 7% Nausea 9% 6% Diarrhea 6% 4% Hyperhidrosis 6% 1% Hot Flush 3% 2% Tremor 1% <1% Chills 1% 0%

*Adverse reactions occurring in at least 1% of patients receiving RELISTOR injection 12 mg subcutaneously once daily and at an incidence greater than placebo. **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness During the 4-week double-blind period, in patients with OIC and chronic non-cancer pain that received RELISTOR every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily RELISTOR dosing. Use of RELISTOR injection 12 mg subcutaneously every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 2) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%). The safety of RELISTOR injection was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with OIC and chronic non-cancer pain (Study 3). Patients were allowed to administer RELISTOR injection 12 mg subcutaneously less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48-week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 2. Additionally, in Study 3, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR. Opioid-Induced Constipation in Adult Patients with Advanced Illness The safety of RELISTOR injection was evaluated in two, double-blind, placebo-controlled trials in adult patients with OIC and advanced illness receiving palliative care: Study 4 included a single-dose, double-blind, placebo-controlled period, whereas Study 5 included a 14-day multiple dose, double-blind, placebo-controlled period. The most common adverse reactions in adult patients with OIC and advanced illness receiving RELISTOR injection are shown in Table 6 below. Table 6: Adverse Reactions from All Doses in Double-Blind, PlaceboControlled Clinical Studies of RELISTOR Injection in Adult Patients with OIC and Advanced Illness* (Studies 4 and 5) RELISTOR Injection Placebo Adverse Reaction n = 165 n = 123 Abdominal Pain** 29% 10% Flatulence 13% 6% Nausea 12% 5% Dizziness 7% 2% Diarrhea 6% 2%

*Adverse reactions occurring in at least 5% of patients receiving all doses of RELISTOR injection (0.075, 0.15, and 0.3 mg/kg) and at an incidence greater than placebo **Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness The rates of discontinuation due to adverse reactions during the double-blind, placebo-controlled clinical trials (Study 4 and Study 5) were comparable between RELISTOR (1%) and placebo (2%). Postmarketing Experience The following adverse reactions have been identified during post-approval use of RELISTOR injection. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Gastrointestinal Perforation, cramping, vomiting. General Disorders and Administration Site Disorders Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported. DRUG INTERACTIONS Other Opioid Antagonists Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. Drugs Metabolized by Cytochrome P450 Isozymes In healthy subjects, a subcutaneous dose of 0.3 mg/kg of RELISTOR did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate. USE IN SPECIFIC POPULATIONS Pregnancy The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise pregnant women of the potential risk to a fetus.

Lactation Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness of RELISTOR tablets and injection have not been established in pediatric patients. Geriatric Use In clinical studies of RELISTOR tablets, no overall differences in effectiveness were observed. Adverse reactions were similar; however, there was a higher incidence of diarrhea in elderly patients. In clinical studies of RELISTOR injection, no overall differences in safety or effectiveness were observed between elderly patients and younger patients. Based on pharmacokinetic data, and safety and efficacy data from controlled clinical trials, no dosage adjustment based on age is recommended. Monitor elderly patients for adverse reactions. Renal Impairment In a study of subjects with varying degrees of renal impairment receiving RELISTOR injection subcutaneously, there was a significant increase in the exposure to methylnaltrexone in subjects with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault) compared to healthy subjects. Therefore, a dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment. No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment (creatinine clearance greater than 60 mL/minute as estimated by Cockcroft-Gault). Hepatic Impairment Tablets In a study of subjects with varying degrees of hepatic impairment receiving a 450 mg dose of RELISTOR tablets, there was a significant increase in systemic exposure of methylnaltrexone for subjects with moderate (Child-Pugh Class B) and severe (Child-Pugh Class C) hepatic impairment compared to healthy subjects with normal hepatic function. Therefore, a dosage reduction of RELISTOR tablets is recommended in patients with moderate or severe hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). Injection There was no clinically meaningful change in systemic exposure of methylnaltrexone compared to healthy subjects with normal hepatic function. No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions. OVERDOSAGE A study of healthy subjects noted orthostatic hypotension associated with a dose of 0.64 mg/kg administered as an intravenous bolus. Monitor for signs or symptoms of orthostatic hypotension and initiate treatment as appropriate. If a patient on opioid therapy receives an overdose of RELISTOR, the patient should be monitored closely for potential evidence of opioid withdrawal symptoms such as chills, rhinorrhea, diaphoresis or reversal of central analgesic effect. NONCLINICAL TOXICOLOGY Carcinogenesis Oral administration of methylnaltrexone bromide at doses up to 200 mg/kg/day (about 81 times the subcutaneous maximum recommended human dose (MRHD) of 12 mg/day based on body surface area) in males and 400 mg/kg/day (about 162 times the subcutaneous MRHD of 12 mg/day) in females and in Sprague Dawley rats at oral doses up to 300 mg/kg/day (about 243 times the subcutaneous MRHD of 12 mg/day) for 104 weeks did not produce tumors in mice and rats. Mutagenesis Methylnaltrexone bromide was negative in the Ames test, chromosome aberration tests in Chinese hamster ovary cells and human lymphocytes, in the mouse lymphoma cell forward mutation tests and in the in vivo mouse micronucleus test. Impairment of Fertility Methylnaltrexone bromide at subcutaneous doses up to 150 mg/kg/day (about 122 times the subcutaneous MRHD of 12 mg/day; about 3.3 times the oral MRHD of 450 mg/day) was found to have no adverse effect on fertility and reproductive performance of male and female rats. Animal Toxicology and/or Pharmacology In an in vitro human cardiac potassium ion channel (hERG) assay, methylnaltrexone caused concentration-dependent inhibition of hERG current. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). For more information, go to www.Relistor.com or call 1-800-321-4576. Based on 9493104 11/2018 Salix Pharmaceuticals 400 Somerset Corporate Blvd. Bridgewater, NJ 08807 USA www.salix.com

Manufactured for:

Under license from:

Progenics Pharmaceuticals, Inc. Tarrytown, NY 10591 U.S. Patent Information: For Injection: U.S. Patent Numbers: 8,247,425; 8,420,663; 8,552,025; 8,822,490; 9,180,125; 9,492,445 and 9,669,096 For Tablets: U.S. Patent Numbers: 8,420,663; 8,524,276; 8,956,651; 9,180,125; 9,314,461; 9,492,445 and 9,724,343 Relistor is a trademark of Salix Pharmaceuticals or its affiliates. REL.0082.USA.19

Our next article brings two things to mind—first: now more than ever patient year is nearing its end, and education is of critical importance; second: Kevin L. Zacharoff the world of pain management has been we may often discount chronic pelvic pain as quite a tumultuous one. After much controa bona fide, functionally disabling medical versy the CDC advised against misapplication of the Guideline for Prescrib- condition. Drs. Jorge Carrillo and Georgine Lamvu detail the prevalence ing Opioids for Chronic Pain (released in 2016), specifically with respect to of this painful condition and its societal economic burden. While we may avoiding hard limits and “cutting patients off” or rapid or forced tapering think this is a problem solely among women, it occurs in men as well. A of chronic opioid therapy. We also sadly said goodbye to the American Pain strong and valid case is made for utilizing a biopsychosocial approach to Society, whose President stated, “It’s the perfect storm and now pointless managing chronic pelvic pain, a multimodal approach to treatment planto continue operations just to defend against superfluous lawsuits.” We ning, and managing patient goals and expectations through education. If watched fentanyl firmly establish its role as the leader of opioid-related you’re looking to learn more about this not uncommon type of pain, this overdose deaths. We continued to search for rational, nonreactive ways to article is for you. make sure that chronic pain patients aren’t deprived of medications they need because of the high prevalence of misuse, abuse, and addiction. The This issue’s Pundit Profile spotlights a dynamic and driven physician’s assiscurrent issue of PWJ offers answers for the year ahead. tant, Jeremy A. Adler. As someone who also wanted to pursue a career in medicine since childhood, I can certainly relate to Jeremy’s passion and Whether we like it or not, we must admit that there will be people who persistence. His accomplishments, perspectives, and desire to make a difrecreationally use opioid substances—prescription or not. Dr. Beatrice ference have defined his personal and professional life, and I think you’ll Setnik presents a detailed exploration of real-world abuse through enjoy “meeting” him. interviews with 5 recreational opioid users in Montreal, Canada. These interviews focus on the role and effectiveness of abuse-deterrent for- Dr. Alexis LaPietra is the focus of this issue’s Next Generation. When I mulations of opioid analgesics and the willingness of recreational users consider the qualities essential for future leaders of the pain management to manipulate them. Readers are likely to find the interviewed users’ field, I find that Alexis has them all. She is someone who wants to empower perspectives and perceptions about safety, manipulation, and routes of her peers, stimulate progress through innovation, is obviously a highly administration fascinating and thought provoking. Given the state of the energetic person, and is willing to be judged by changes she is able to make opioid epidemic in North America, it’s incumbent on us to know more over the course of her career. I hope you enjoy learning more about a key about what may or may not work when it comes to mitigating aberrant opinion leader of the present and the future. drug-related behaviors. Also worthy of mention in this issue of PWJ: my first installment of what It’s probably fair to say that most of us have been trained (if we have been will be a recurring segment called Back to the Basics, for people seektrained at all) to treat chronic pain as if it were the same as acute pain: in a ing basic foundational pain education; and an op-ed from Jessica Geiger reductionistic way. Our next article is by Dr. Mel Pohl, a family practitioner, about how legislation, guidelines, and reimbursement practices can impact and Becky Curtis, a health/wellness coach. They wrote this article with the patient care. intention of grounding our thinking about managing chronic pain. Together they present a detailed look at how acute and chronic pain differ and how Common themes in this issue: the importance of patient education, subthe approach to their treatment should differ as well. They encourage stance abuse, special patient populations, and the complexities associated clinicians to think about what lies “below the surface” of the tip of the with implementing standardized, safe, and effective pain care. Despite the pain management iceberg, and offer ideas and scientifically based practice turbulent year, some things never change—it’s up to us to do the best we paradigms to help battle the hopelessness and lack of compassion that can for people with pain. Maybe now more than ever. chronic pain patients often face daily. Kevin L. Zacharoff MD, FACIP, FACPE, FAAP When it comes to managing acute pain, one may think that inpatient management is generally easier than outpatient management. You might be surprised to find out that it’s not that simple. The challenges associ- Kevin L. Zacharoff is Faculty and Clinical Instructor at suny Stony Brook School ated with inpatient management and our reasonably low level of success of Medicine in New York, and is Ethics Committee Chair at St Catherine of Siena despite being able to control the inpatient environment is quite troubling Medical Center in Smithtown, New York. to me. Mechele Fillman sheds important light on the complicated processes involved in developing an acute pain service in the hospital setting. From creating rational policies and procedures to conforming to requirements placed on the institution by agencies such as the Joint Commission, something that may initially seem like a “no-brainer” could be a massive undertaking, especially in a community hospital setting. This article is a must-read for people embarking on this particular journey; it’s always helpful to learn from other people’s experiences (and pain).

PWJ | www.painweek.org

Q 4 | 2019

PaiNWeeKeNDâ&#x201E;¢ ReGiONaL CONFeReNCe SeRieS

2020

pain management for the main street practitioner visit www.painweekend.org for more information.

Jorge F. Carrillo MD, FACOG

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Jorge Carrillo is a Board Certified OB/GYN who received training in adult learning and medical education by completing a 2-year Dean’s Teaching Fellowship at the University of Rochester in New York. He is also a minimally invasive gynecologic surgeon and chronic pelvic pain specialist at the Orlando VA Medical Center and an Associate Professor at the University of Central Florida College of Medicine in the Department of Obstetrics and Gynecology in Orlando. Coauthor: Georgine Lamvu, md, mph, gynecologic surgeon and pelvic pain specialist at the va medical center in Orlando, Florida.

Becky L. Curtis NBC-HWC

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Becky Curtis is a National Board Certified Health and Wellness Coach and is founder and CEO of Take Courage Coaching, which specializes in pain management coaching. Coauthor: Mel Pohl, MD, Addiction Specialist, Clinical Assistant Professor at the University of Nevada School of Medicine in the Department of Psychiatry and Behavioral Sciences, and Chief Medical Officer at the Las Vegas Recovery Center.

Mechele Fillman MSN, NP

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Mechele Fillman is a Nurse Practitioner currently in the process of building the infrastructure for an acute pain service at Christus St. Vincent’s Regional Medical Center in Santa Fe, New Mexico. Her previous roles included expanding the inpatient pain service for Stanford Health Care in California and starting her first inpatient pain service in 2008 at St. Joseph’s Hospital in Denver, Colorado

Beatrice Setnik PhD

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Beatrice Setnik is an Adjunct Professor at the University of Toronto, Department of Pharmacotherapy & Toxicology. She is also Chief Scientific Officer at Altasciences, a full-service contract research organization offering biopharmaceutical companies early drug development solutions including preclinical safety testing, clinical pharmacology, bioanalysis, and research services. Dr. Setnik has been working in the area of clinical drug development and CNS research for over 15 years and is a leading expert in the area of abuse and dependence evaluation.

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home with youâ&#x20AC;&#x201D;

By Beatrice Setnik phd

Exploring Opioid Abuse-Deterrent Methods From the Laboratory to the Real User

By Beatrice Setnik phd

key topic

Prescription opioid abuse involves an array of behaviors related to the administration of the drug by both intended and unintended routes that can result in serious health consequences. Manipulations of a formulation involve either crushing/powdering the drug for intranasal use or solubilizing for injection. In 2015, the FDA released a guidance describes the types of laboratory and clinical assessments required to determine the effectiveness of abuse-deterrent formulations. Because methods of drug abuse evolve in the real world, it is critical to monitor changing trends and reflect these in the methods used to assess abuse deterrence. Monitoring can be done by surveys, interviews, media and literature reports, surveillance databases, and via the internet. An interview with 5 recreational opioid users (4 men, 1 woman, ages 28–49) was held in Montreal, Canada on August 1, 2019. During the interview, subjects were asked about their recreational opioid use history and their behaviors related to opioid administration. Highlights from the group discussion are presented here.

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Background Behaviors related to prescription opioid abuse and misuse are

complex and involve administration of opioids by both intended and unintended routes. The reasons for prescription opioid abuse and misuse are also varied. In 2017, 11.1 million persons in the United States aged ≥12 reported past year prescription opioid (pain reliever) misuse, with hydrocodone, oxycodone, and codeine reported as most frequently misused.1 The reported reasons for misuse were predominantly to treat pain (62.6%), feel good/get high (13.2%), and relax/relieve tension (8.4%). The sources of the prescription opioids were mainly from friends or family (given, bought, or taken; 53.1%) or from a prescription by one doctor (as opposed to doctor shopping) (34.6%).1

“Because methods of drug abuse evolve in the real world, it is critical to monitor changing trends and reflect these in the methods used to assess abuse deterrence.” The routes of abuse also vary by drug user and by type of opioid. For example, a previous study reported most frequent oral use for hydrocodone and oxycodone, whereas intranasal use was most often reported for oxymorphone, and intravenous use for hydromorphone and morphine. The route of administration predominantly endorsed for fentanyl use was “other.”2 Altering formulations for unintended routes of administration requires some manipulation of a formulation to either crush/powder the drug for intranasal use or solubilize for injection. To circumvent the abuse/misuse of prescription drugs by unintended routes of administration, abuse-deterrent features have been introduced. In 2015, the FDA published a final guidance on the assessment of abuse-deterrent opioids.3 The guidance covers the degree of premarketing testing that needs to be conducted on such formulations to demonstrate their ability to resist common manipulation methods and reduce abuse potential when administered by various routes. Such methods divide these studies in categories, including in vitro laboratory testing (category 1), which spans a large degree of physical and chemical manipulations to prepare a test drug for different routes of Q 4 | 2019

administration, clinical pharmacokinetic testing (category 2), and clinical human abuse potential studies (category 3). The methods used to test abuse-deterrent formulations (ADFs) are often adapted to include emerging trends of use in the real world. Novel methods are frequently found on internet forums, where users post methods on how to take drugs of abuse or how to defeat the ADFs. For example, the method of crisping involves heating a tablet in an oven or microwave prior to crushing or solubilizing. Another example is the trend of vaping. Laboratory methods will also include analyses of vaporizing, heating, and burning drug formulations to determine whether the active drug can be recovered in any significant amounts. Clinical pharmacokinetic trials are then conducted to ensure that a formulation is not compromised by food and/or alcohol. In addition, human abuse potential studies in nondependent recreational opioid users are conducted to determine if the ADF reduces drug liking and other subjective drug effects that are desirable to drug users, such as feeling high. These studies are conducted under both intended and unintended routes of administration.3 Currently, there are several marketed ADFs, www.painweek.org | PWJ

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and recent studies have shown that deterrence approaches can reduce behaviors and fatalities related to abuse in the real world.4-6 It is critical that real-world behaviors are continuously monitored to evaluate the robustness of abuse deterrence and emerging methods of abuse. It is often beneficial to survey internet posts and conduct interviews with abusers to learn of new methods, trends, and drugs that appear regionally. Trends in abuse can be influenced by factors including local availability of both licit and illicit drug supply.

Group Discussion with Recreational Opioid Users On August 1, 2019, a group discussion with 5 recreational opioid users was recorded at Altasciences in Montreal, Canada. The purpose of the discussion was to learn about the users’ history, habits, and methods of administration as they related to their self-reported recreational prescription opioid use. The subjects were self-reported recreational opioid users who were not physically dependent on opioids and were identified using a database of subjects who have participated in past human abuse potential studies. All subjects provided informed consent to participate in the discussion and were compensated for their time and travel costs. See Table.

Table. Study Participants Gender

Age

Prescription Opioid Use Origination

Male

Rx back pain

Male

Recreational oral use

Male

Rx post-operative

Male

Rx skateboarding injury

Female

Recreational oxycodone (10 mg)

Types of Opioids Used Most subjects had used more than 1 type of opioid. The drugs mentioned by name in the discussion were:

○○ Oxycodone ○○ Morphine/morphine sulfate ○○ Percocet ○○ Hydromorphone ○○ Codeine ○○ Hydrocodone ○○ Fentanyl

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Delivery Methods The subjects reported using various routes of administration for opioid use. All subjects in our interview acknowledged oral use; 1 described it as “the good old-fashioned way” and utilizes it when the ADF makes alternative delivery undesirable. Four subjects acknowledged intranasal use, with levels of complexity behind the manipulation of the drug. All 4 subjects described simple crushing or cutting followed by crushing. One subject described a detailed, 2-phase chemical process for preparing morphine for smoking (phase 1) or snorting (phase 2), which required an additional step of baking. Two subjects acknowledged smoking opioids. One subject acknowledged (assisted) intravenous (IV) administration, on one occasion. The stated perception was that it allowed for a faster onset, which also subsided more quickly, and was otherwise an identical experience as the oral route. Therefore, the subject did not recommend the IV route. One subject discussed different approaches to oral use: stacking—taking multiple doses over time to intensify or sustain effects, and parachuting—wrapping the crushed or powdered drug in paper before swallowing in order to achieve a faster onset.

Manipulation Subjects reported levels of willingness to manipulate drug formulation for recreational uses. Unintended routes of administration required some degree of formulation manipulation/ tampering, and the reported methods varied, from simple crushing to complex chemical extractions, depending on the type of opioid, the formulation, and the intended route of administration. The subjects agreed that recipes and methods, as well as opioids for purchase, can be found on the internet. One subject reported using a multistep chemical extraction processes to prepare a free-base of morphine for intranasal use, as well as a method of microwaving to bypass an extended-release formulation. Most subjects stated they would not spend more than 5 minutes manipulating for dosing. One subject said that if the drug-taking was being done in a group with all members partaking, the preparation became part of the experience, and he would be willing to invest hours. All subjects agreed that opioids (unless mixed with hallucinogens or stimulants) would not be a drug of choice for a social situation. One subject routinely mixed opioids with stimulants while skateboarding, for the combined energy-enhancing and analgesic affects. Two subjects mentioned using opioids alone, preparing their physical environment as “me-time” or a “minivacation.” Q 4 | 2019

Safety Considerations The participants interviewed expressed differing levels of concern regarding the safety of their drugs, and their own safety in drug use. Four subjects stated that they were purchasing drugs illicitly, mostly through friends, acquaintances, and occasionally on the street. Two acknowledged being aware of their availability on the internet or dark web, but did not acknowledge having used this avenue to purchase. One reported obtaining only legitimately prescribed medication, partly because of a concern over the purity of street drugs and the potential contamination by fentanyl. When asked about the safety concerns when exposed to high potency fentanyl in adulterated opioids, most subjects did not seem concerned. One subject stated that he was not concerned because he had simply not encountered fentanyl before. Another subject described the availability of fentanyl testing at supervised injecting facilities (in Canada), where he and his peers frequently went. He also mentioned the availability of naloxone and described free training on its proper use, which increased his sense of safety. When questioned about their sources of information regarding manipulation/preparation for dosing, most mentioned friends, the internet, and YouTube videos. All acknowledged combining opioids with other drugs, ranging from alcohol to tobacco, cannabis, stimulants, and other opioids. There were some obvious misconceptions in the group about the potential for self-harm in their drug use. Examples of subjects’ reported misperceptions included:

○○ The belief that opioids can be safely administered by unintended routes ○○ The belief that use of a microwave can “melt away the harmful substances” on an extendedrelease formulation ○○ The belief that combination drugs that contain acetaminophen (specifically paracetamol) should be avoided only because of the risk of liver damage ○○ Lack of concern of fentanyl exposure since they had not experienced it

Abuse-Deterrent Formulations Most participants had experience with ADFs. Three subjects said that “anything can be crushed if you try hard enough” and one was confident that his chemical processes facilitated extraction. One participant stated that she “had heard that it’s possible but would never try” to tamper with an ADF for intranasal delivery. General consensus was that formulations that jell when mixed in solution and formulations that clog the nasal Q 4 | 2019

passages were most difficult to circumvent. When confronted with these, most agreed they would choose an oral route.

Conclusion Although this interview was conducted with a small sample size, many of the opinions expressed correspond with larger surveys of drug abuse and misuse, such as the National Survey on Drug Use and Health.1 The demographics of opioid users vary widely across gender, race, and age. As seen from other data and this interview, the routes of administration also vary amongst users. Unintended routes of administration require some degree of manipulation/tampering, and methods differ widely depending on the type of opioid, the formulation, and the intended route of administration. Drug users can have very advanced knowledge of chemistry or may find recipes and methods easily on internet forums that illustrate simple to complex methods for drug extraction. As evidenced by this interview, often the risks of opioid abuse are not clear, or users have a false sense of security regarding the safety of their drug use. Some reported taking precautions by having naloxone readily available or using fentanyl tests to detect adulterated product. Interviews and interactions of this nature, with recreational drug users, are helpful in identifying trends and motives underlying prescription opioid abuse and enable more thorough laboratory and clinical methods to evaluate the robustness of ADFs in an environment where drug using behaviors adapt and change over time. References: 1. Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: results from the 2017 National Survey on Drug Use and Health (HHS Publication No. SMA 18–5068, NSDUH Series H-53). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2018. Available at: www. samhsa. gov/data/. 2. Butler SF, Black RA, Cassidy TA, et al. Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm Reduct J. 2011;8:29. 3. Abuse-Deterrent Opioids — Evaluation and Labeling Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Clinical Medical. April 2015. 4. Cicero TJ, Mendoza M, Cattaneo M, et al. Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients. Postgrad Med. 2019;131(3):225–229. 5. Coplan PM, Chilcoat HD, Butler SF, et al. The effect of an abuse-deterrent opioid formulation (OxyContin) on opioid abuse-related outcomes in the postmarketing setting. Clin Pharmacol Ther. 2016 Sep;100(3):275–86. 6. Cassidy TA, Thorley E, Black RA, et.al. Abuse of reformulated OxyContin: Updated findings from a sentinel surveillance sample of individuals assessed for substance use disorder. J Opioid Manag. 2017;13(6):425–440.

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By Becky Curtis NBC-HWC / Mel Pohl MD

Even though we know the facts about chronic pain and how it works, we often focus on the obvious 20% while ramming into the 80% conundrum below.

By Becky L. Curtis NBC-HWC / Mel Pohl MD

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An ominous form was looming large on the horizon of the pain management world. Off in the distance we saw it coming closer and closer. Faster and faster we steamed ahead as the distant bump grew into a towering mountain. Suddenly someone shouted “ICEBERG!” Quickly we steered starboard and saw with relief that the nose of the ship had cleared the edge of the obstacle. But then a sudden jolt erupted from the depths as we struck the unseen enormity of what lay below the surface. Beneath that surface, the problem was bigger than we imagined and now we were sinking. The problem we saw, and tried to solve, was not the real problem after all. It was but the tip of the iceberg. The thing about icebergs is that what you can see is only 20% of the problem. Below the surface is a monstrous mass of ice, and it is this other 80% that so often sinks us. This is true of chronic pain as well. Even though we know the facts about chronic pain and how it works, we often focus on the obvious 20% while ramming into the 80% conundrum below. We represent two unique perspectives on the issue of pain management: Mel Pohl—a family practice doctor with a specialty in addiction medicine with more than 15 years’ experience in pain and addiction recovery; Becky Curtis— a certified health and wellness coach who has worked for

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the past 10 years to apply the discipline of coaching specifically to the problem of pain management. A natural knee-jerk response is to treat persistent pain as if it were acute pain. We often do this because the patients want us to: they want us to “fix it.” We dutifully step into the hero role and try to help find “the cause of their pain” so it can be treated and “cured.” What we miss in this process is the obvious fact that chronic pain is “chronic.” Synonyms for the word “chronic” are “persistent, long standing, long term, incurable, immedicable” (unable to be healed or treated, incurable). The antonym for chronic is “acute.” Is it any wonder that the mainstream push to cure chronic pain crashes us nose-first into an iceberg? This amounts to nothing less than the definition of insanity: Trying the same thing over and over again expecting a different result. When it comes to treatment, the only thing acute and chronic pain have in common is the word pain. They represent totally different processes. In this article, we will discuss basic principles of diagnosing and treating chronic pain. Dr. Pohl will review the neurophysiology of chronic pain and clinical strategies for effective treatment of that condition. Ms. Curtis will illustrate these principles and strategies with case studies from her broad experience as a pain coach.

Q 4 | 2019

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Acute Pain vs Chronic Pain

Acute pain is a signal from the hardware of the nervous system related to tissue damage. It’s like an alarm going off. It tells you something is wrong and you should do something about it. When the wound is treated, and the tissue damage heals, 95% of the time the pain goes away. Which leaves us with the observation that acute pain is a useful, functional, and temporary signal. Chronic pain is an entirely different process. It may or may not start with tissue damage, but the real significance of the experience of chronic pain is that the signal is transmitted to the brain and ends up being a process that occurs in the limbic system where emotions are mediated. By focusing on the tip of the iceberg, clinicians have medicalized chronic pain as if it were only more acute pain. We do MRIs and functional MRIs and CTs with contrast and stand the patient on his/her head and do another MRI or injection, and we “prove” that the cause of the pain is, let’s say, a disc, and then we go after it with a needle—epidurals and radiofrequency ablations—and this often helps temporarily, but often doesn’t. We clobber the pain with a blunt object like an opioid, and at the end of the process we have a patient who is not responding, has a persistence of pain, is dependent on opioids, and then we often go after the tissue damage with a knife. What we frequently see when a patient is referred to a functional restoration program is that surgeons feel that they have taken care of the problem surgically, but the patient is still suffering. Sadly, the messaging to the patient becomes that, since the problem has been surgically fixed, the pain must be “all in your head. You’re histrionic!” Or worst of all “Your pain isn’t real.” In the spirit of best practices, I would like to suggest 5 things I have learned in the course of working as a family practice doctor and certified addiction specialist in a clinical setting:

1. The pain is real

An article by Newton et al speaks powerfully about the cost of disbelief: the mistrust that develops between the medical team and a patient when it is implied that a patient’s pain isn’t real.1 Pill seeking isn’t necessarily nefarious. It’s all the patient knows how to do to try and relieve pain. And when providers disbelieve that a patient’s pain is real, they do the patient a disservice. We must start out with a position of belief, that the pain is real. A clinician’s first job is to listen, then to use certain simple trainable skills to move that patient out of the rut of suffering.

2. Thoughts and emotions drive the experience of pain

I am often asked by colleagues who refer patients, families, and other clinicians if the patient’s pain is physical or emotional, and I answer, “Yes, the pain 24 PWJ | www.painweek.org

is physical, and of course the pain is emotional.” It is not an “either/or” question. It is “both+and.” 80% of the experience of pain is emotional and cognitive, yet usually we end up focusing on the 20% that’s above the surface and, in missing the bulk of the problem, we also miss the bulk of the solution. The process of chronic pain is in the insula, the prefrontal cortex, the nucleus accumbens and the ventral tegmental area. It is different from acute pain. Acute pain occurs in the thalamus, the relay station of the brain. There are several studies from Northwestern University showing that the thalamus lights up with acute pain, and the nucleus accumbens and ventral tegmental areas light up with chronic pain.2,3 The nucleus accumbens and ventral tegmental area are where we experience motivation and reward, and where addictive substances act. There’s a pain process related to hippocampal inputs of the memory, thoughts, anxiety, fear, and depression that come along with a physical experience and end up creating this conundrum. It’s a complex process and yet our medical system treats it like it’s simple, as if it’s acute pain, and we go after it as a unimodal condition. We separate mind and body and this doesn’t make sense. We need to treat the whole patient—mind and body. It’s hard to explain to patients and other providers without sending the message that we don’t believe the pain is real. I explained the role of thoughts and emotions to one patient and she said, “I’m checking out of this place! You’re full of crap! You’re saying my pain is all in my head!” And I said, “Well, you have chronic headaches. So, where else would your pain be?” But it was as if I was insulting her. When I explained that chronic pain is a brain experience involving thoughts and feelings, she heard me saying that her pain wasn’t real. We must begin by believing the patient and affirming the reality of their experience of pain or we will completely miss addressing the larger emotional part of their pain experience.

3. Opioids often make the pain worse

Although I’m not an opiate nihilist, I’m starting to lean in that direction because I see the negative consequences of long-term opioid use. I work in a tertiary care center and we see people who have not done well on opioids. I know there are people who do. But opioids do several things: there is a rollercoasterlike effect of ON and then OFF that may cause the development of tolerance and physical dependence. If somebody is physically dependent on a drug, they are going to have a re-emergence of symptoms between doses. People with chronic opioid use often have a higher pain level. Further, opioids cause opioid induced hyperalgesia—glutamate goes up, NMDA goes up— causing a stimulation of the central nervous system.4,5 This increase in sympathetic activity results in the activation of glial cells elevating the tone of the nervous system even more. Opioids are proinflammatory in most patients. Clinically, I have found that most patients experience less pain off their opioids than on. One thing that happens at the Las Vegas Recovery Center, where Q 4 | 2019

I am the Chief Medical Officer, is that patients who come to us believe that they need their opioid. They “know” this because they’ve tried to go off, they’ve even gone a whole day without the opioid, and their pain shot through the roof. Therefore, they conclude they cannot come off opioids. Increased pain when lowering or discontinuing the opioid is the result of physical dependence. Physical dependence may be associated with addiction, but it isn’t, necessarily, the same as addiction. It’s a complex dependence process between pain relief and reward.6,7

4. Treat to improve function

When I meet a patient, I don’t ask “What’s your pain score?” Rather than “What’s the matter?” I ask “What matters to you? How far can you walk? Are you engaged in your life? Do you go to work? Are you in bed part of the day? Are you in bed more now than you were before opioids?” Approaches to pain that focus on the pain treat the tip of the iceberg and often make matters worse. Emphasizing function provides a more appropriate focus.

5. Expectations influence outcomes

Pessimists have a more realistic view of life, but optimists live longer. A National Academy of Science study suggests that people who are optimistic sleep better and live longer.8 Pain focus and negative thoughts actually increase a person’s experience of pain and contribute to suffering. Research by Moskowitz has demonstrated that in chronic pain patients the 9 areas of the brain dedicated to experiencing pain have actually recruited more brain cells to participate in the process. This neuroplastic change has a significant role to play in how we treat chronic pain as well.9

Everything I know about pain I learned by accident, literally. In the summer of 2005, a car accident introduced me to the science of persistent pain firsthand. And in my quest for solutions I became an avid student. At the scene of my accident I sat in the wreckage of my SUV unable to move from the neck down. I seriously thought I would spend the rest of my life in a wheelchair but the optimistic words of my neurosurgeon a few days later served as the inspiration to help move me forward: “You’re going to walk again,” he said. And I believed him. My recovery went extremely well. Every day was an unending process of improvement and growth. Yes, I had an incomplete C-4 spinal cord injury, pins and needles nerve pain, and Brown-Séquard syndrome, but bit-by-bit I was getting my life back. Life wasn’t perfect, but I could walk, do the basic functions of life and kept improving every day. Then two years out, the nerve pain progressed into an overwhelming neck-down burning Q 4 | 2019

inside and out. An MRI revealed a syrinx at the site of my injury and my doctors were quite sure this was the cause of my sudden increase in pain. Optimistically, I hoped this fluid-filled cyst could be drained and I would be fine, but my doctor informed me that it was inoperable and I would have this condition the rest of my life. With surgery out of the question we turned to medication. Rather than decreasing my suffering the medications took away my ability to cope and left me more miserable. As Howe and Sullivan write, “There is no evidence chronic opioid therapy benefits most people… Unfortunately, opioids remain the de facto treatment for most workers with chronic pain.”10 A few agonizing months later I was sent to a functional restoration program where I learned that pain is an experience of the brain. and I could do things to manage the experience. While learning about the science of pain I discovered the power of exercise to help me manage it. At first, I could only do a few minutes on the elliptical, but gradually I worked my way up. Learning basic modalities like sleep hygiene, diaphragmatic breathing, the importance of a low inflammation diet, and positive thought patterns to help end my catastrophizing gradually set me free from my pain. It was as if I had pulled pain out of the driver’s seat and was taking control again. The process helped me shift from a passive “cure me” mentality to an active “I’ve got this” kind of perspective. After I returned home, I discovered that a fellow patient wasn’t doing as well. After coming home from the program, she had lapsed back into her old ruts, and was suffering as bad—if not worse—than she had. Wanting to help her, I tapped into my previous training as a life coach and began coaching her back into managing her pain. She began to retake control of her life and reimplement her favorite modalities. She was amazed how effective diaphragmatic breathing was at helping her relax and decrease her pain. Exercise helped increase her blood flow, decreased muscle tension, released beneficial neurotransmitters, and helped restore core strength and skeletal support. Lessons on sleep hygiene helped her turn off her TV at night, settle and calm her body before bed, and resulted in a significant increase in restful sleep that also helped improve her experience of pain. Through this process she began to assume the driver’s seat for herself and reclaimed her life once again. Around this time a vocational rehab counselor asked me an empowering question, “What do you want to do with your life?” I was 3 years out from my accident and this was the first time anyone had ever asked me that question. Most people just assumed I would sit in a recliner for the rest of my life watching TV. Remembering the success I had in coaching my friend, I said, “I want to become a pain management coach.” “Do you know where you can get trained for that?” my counselor asked. “I don’t think it exists,” I responded. “But if I can get some more coach training, I will create it!” And for the last 10 years that is what I’ve done. While searching for the best evidencebased modalities for pain management, I began to www.painweek.org | PWJ

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create the specific discipline of pain management coaching because there was a gap between the best advice patients were getting in the clinic and the application of that advice in their own homes. As I coached people, I found that coaching was the bridge that helped them step over to the other side of success. I wrote pain education lessons and perfected my coaching skills with new clients. My results were good but people questioned if it was just me or could I train others to do what I did. I began assembling and training a team of pain management coaches because I knew it was the missing piece in the pain management puzzle Over the past 10 years, my team and I have used our telephonic coaching program to coach injured workers, veterans, and others to successfully manage their pain, reduce the use of opioids, return to work, and regain their lives. By using motivational interviewing techniques, coaches help move clients out of a passive “cure me” mentality into an active “I can manage my own pain” mindset. People who are coached in this way succeed in ejecting pain from the driver’s seat and throwing it in the trunk where it belongs. Coaching clients over time takes advantage of the science of chronic pain. As Dr. Pohl has pointed out, the experience of pain increases as the patient focuses on and catastrophizes it. The science of neuroplasticity teaches us that “The longer we have been negative, angry and passive, the more brain change we will need to make. Because of the plasticity in our brain, everything is reversible. In the same way that muscles and joints can be made more healthy and robust, so too can the homunculus arrangements in your brain.”11 A principle of neuroplasticity is that “What we focus on, we empower and enlarge.”12 But the opposite is also true: “What we don’t use, we lose.” This is why a coach approach that reframes clients’ experience from negative thoughts toward a positive perspective succeeds in helping them permanently decrease their experience of pain. Coaching helps facilitate the shift from a passive mindset to actively realizing “I have everything I need right here.”

Becky is my hero, and what she and her coaches do really works. As she has pointed out, one of the things that really holds patients back is a pain identity. “This pain is killing me.” Have you ever heard your patients say that? When a patient says that to me, I want to ask, “What will be the cause of death on your death certificate?” For patients like this, pain becomes their identity. What clinicians can do with patients like this is work to help them separate from “You are not the pain” and change to “You are a person with a condition, and you have a job to do, and you have skills.” One way to help people move out of pain defining who they are is to use acceptance commitment 26 PWJ | www.painweek.org

therapy (ACT). Steven Hayes and his group from the University of Nevada, Reno has done some great work on this.13 ACT helps patients learn what is valuable to them and how to commit to it. Cognitive behavioral therapy (cbt) also has a great evidence of its efficacy in pain management by helping clients reframe negative thoughts.14 At Las Vegas Recovery Center, we seek to be creative with alternative complementary therapies. As Becky has said, motivational interviewing works well by taking a patient’s desire to change and moving them towards a healthy outcome. 12 step programs can give people tools to deal with addiction as well as manage pain. And modalities like coaching that promote selfmanagement and emphasize mindfulness have been quite successful.15 When it comes to self-management, I like to begin with a Pain Self Efficacy Questionnaire (PESQ)16 that has patients rate themselves in relation to statements like “I can walk as far as I need to. I can sleep well. I can go on vacations. I can go back to work.” When they start out, people have a very low score. We try to move them to ownership of internal modalities rather than dependence on external modalities. The best outcomes are realized when patients are personally involved. Pain is not unidimensional but multidimensional, so it is best to work on areas and chip away on the pain one bit at a time. Mindfulness practices are encouraged because they help people readjust and adapt. A patient once said to me, “I can’t meditate because I can’t quiet my mind.” However, mediation is different because it’s a metacognitive process, not CBT, not looking at the thoughts, but just noticing that we are thinking and then redirecting the thoughts to the object of meditation, which is often just the breath. Practicing this is crucial. When we practice, we change our relationship with thoughts so that when “I’m dying of my back pain” comes up, it can be pushed aside or redirected. As Becky has reminded us, “What we focus on we empower and enlarge.” Cells that fire together wire together. The more we can do to help patients focus on the positive, the better. In Full Catastrophe Living, Jon Kabat-Zinn defines mindfulness as “willful directed attention on the present moment.”17 Through mindfulness we can detach from thoughts and become more the observer of the process of thinking. “When you step back from the pain and you notice that you are in pain, does the part of you that notices, is that part of you in pain?” And the truth is, it is not. So, if you can step back, you will have less pain.17 Neuroplasticity is also enhanced by meditative practices. Mediation enhances connections, enhances neurotransmitter levels like epinephrine and serotonin. A recent study about improved quality of life by Dr. Zeidin revealed that after about 4 days of training there is thalamic activation and deactivation of the somatosensory cortex leading patients to essentially respond, “I feel the pain, but I’m not as upset about it. I’m able to let it go.”18 Q 4 | 2019

What we are suggesting is we need to treat the whole person, the mind as well as the body. As Voltaire said, “The art of medicine consists of amusing the patient while nature cures the disease.”19

Case Study on the Power of Words

One of the first people I coached for pain was a man who was 40 years old, had many failed back surgeries, and diabetes. He was on 12 different medications and was socially isolated. What made things worse was that he avoided exercise because of fear. During one of our phone sessions he said, “My doctor told me that, with all this metal in my back from my surgery, if I move the wrong way, I could give myself a spinal cord injury. So I can’t exercise.” I encouraged him to check with his doctor to see if there were any approved exercises he could do. He was approved for swimming. “But,” he said, “I can’t do that.”

“Why not?” I asked. “Because people would make fun of me.” “Why would they make fun of you?” He said, “Well, since we do this by phone, you’ve never seen me. I weigh 400 lbs, and I’m black. And the only pool I can go to is full of white skinny people. They’d all just stare at me and say things.” “What do you think they would say?” I asked. “They would say things like, ‘Just look at him! If I looked like that I wouldn’t come out of the house!’” “You know what I would think if I saw someone doing that?” I asked “No, what?” he quizzed me. “I would think they were brave,” I responded.

Coaching instills courage by calling out strengths. When I called him brave I was able to empower my client with the courage to face the challenge of going to the pool. Once he stood up to the guys in the locker room, he found the strength to continue visiting the pool and exercising with his new found friends. As being more active helped him to better manage his pain he was able to get off his opioids under the supervision of his doctor. He also lost weight and began eating more healthfully. The biggest gain, and something I and my team often see, is that once pain no longer took center stage in his life, he returned to doing the things he loved. Rather than locking himself in his dark home he began socializing with friends he hadn’t seen in quite a while. And he returned to his art studio and workshop where he once again turned out his oil paintings and beautiful cabinetry. Freed from the grip of pain by being empowered to take an active role, clients like this continue to convince me that coaching plays a vital role in helping to shatter the iceberg of chronic pain.

The Paradigm Shift

The goal is to create a paradigm shift from directive extrinsic motivation, where providers tell patients what to do, to intrinsic motivation where the strengths of the person are called out and they begin to take an active role. We use motivational interviewing, ACT, and CBT as tools to help make this happen. We work to elicit from them an intrinsic response by helping them reframe their negative words and thoughts into statements like: “I used to be strong and I would like to feel strong again.” “I am an artist. I would like to have enough energy to go up the one flight of stairs to my art studio.” “I would like to feel clear-headed. I would like to get off my medications.” “I enjoy spending time with the guys at the pool. I feel motivated to get to the pool each day.”

Conclusion

The next time I coached him he said, “Well, it happened.” Sliding to the edge of my seat I asked, “What happened?” “I went to the pool and heard some people talking about me in the locker room,” he replied. “What did they say?” They said, “Did you see that big fat black guy in the pool? If I looked like that there’s no way I’d show my face in public.” “What did you do?” “Well, I got really mad, and decided I was going to go over there and give them a piece of my mind. So I walked over to them and said, ‘Hey, I heard you talking about me.’ They were so scared! And then I said, ‘Do you know why I’m here?’ They said, ‘Uh no, why?’ And I said, ‘I’m here because Becky says I’m brave.’ Then I just turned around and walked away and as I did, I heard one of them say to the other, ‘Who the hell is Becky?’” Q 4 | 2019

As we face the challenge of the iceberg before us, creative and adaptive approaches help us to see beyond the 20% and lead to effectively addressing the 80% below the surface. When we face chronic pain head-on as a chronic condition, we avoid the unnecessary trap of pretending it is an acute condition. To truly survive the iceberg, we must harness the science of pain and educate patients to reframe their experience through coaching and other modalities that empower them to take an active role in owning both the problem and the solution. It takes courage to face the iceberg. People in pain who might feel hopeless must be able to rely on their clinician for understanding and compassion. And once they do, they often find that the best things will come from within. References 1. Newton B, Southall J, Raphael J, et al. A narrative review of the impact of disbelief in chronic pain. Pain Manag Nurs. 2013;14(3):161–171.

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behavioral

2. Baliki MN, Apkarian AV. Neurological effects of chronic pain. J Pain Palliat Care Pharmacother. 2007;21(1):59–61. 3. Hashmi JA, Baliki MN, Huang L, et al. Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain. 2013;136(9):2751–2768. 4. Ballantyne JC, Mae J. Opioid therapy for chronic pain. N Engl J Med. 2003;349(20):1943–1953. 5. Lee M, Silverman SM, Hansen H, et al. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–161. 6. Ballantyne J, Sullivan M, Kolodny A. Dependence is not addiction and “tolerance” declares addiction—reply. JAMA Intern Med. 2013;173(7):595–596. 7. Ballantyne J, Sullivan M. Intensity of chronic pain — the wrong metric? N Engl J Med. 2015;373:2098–2099. 8. Lee LO, James P, Zevon ES, et al. Optimism is associated with exceptional longevity in 2 epidemiologic cohorts of men and women. PNAS. 2019;116(37):18367–18362. 9. Moskowitz M, Golden M. Neuroplastic Transformation Workbook. Neuroplastic Partners; 2013.

11.

Butler D, Mosley L. Explain Pain. 2nd Ed. NOI Group. Adelaide, Australia: 2013.

12. Cameron J. Prayers to the Great Creator: Prayers and Declarations for a Meaningful Life. New York, NY; Penguin; 2008. 13. Dahl J, Wilson K, Luciano C, et al. Acceptance and Commitment Therapy for Chronic Pain. Oakland, CA: New Harbinger Publications; 2005. 14. Broderick JE, Keefe FJ, Schneider S, et al. Cognitive behavioral therapy for chronic pain is effective, but for whom? Pain. 2016;157(9):2115–2123. 15. Curtis RL, Obeso J. Pain management coaching: the missing link in the care of individuals living with chronic pain. J Appl Biobehavior Res. 2017;18(10):1–8. 16. van der Maas LCC, de Vet HCW, Köke A, et. al. Psychometric properties of the Pain Self-Efficacy Questionnaire (PSEQ). Eur J Psycholog Assess. 2012;28:68–75. 17. Kabat-Zinn J. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness. New York, NY: Bantam Books; 2013. 18. Zeidan F, Vago D, Mindfulness meditation-based pain relief: a mechanistic account. Ann N Y Acad Sci. 2016;1373(1):114–127. 19. Wallach J. Interpretation of Diagnostic Tests. 8th ed. Baltimore, MD; LWW; 2000.

10. Howe CQ, Sullivan MD. The missing ‘P’ in pain management: how the current opioid epidemic highlights the need for psychiatric services in chronic pain care. Gen Hosp Psychiatry. 2014;36(1):99–144.

Freed from the grip of pain by being empowered to take an active role, clients like this continue to convince me that coaching plays a vital role in helping to shatter the iceberg of chronic pain.

EXCESS NGF IS ONE OF THE KEY DRIVERS OF CHRONIC PAIN

WHAT HAPPENS HERE

In response to injury or inflammation, cells at the site of pain release a number of biochemical mediators, including prostaglandins, cytokines, and a neurotrophin called nerve growth factor (NGF). NGF plays a key role in driving chronic pain. Excess NGF can change the way nerves signal pain. In the periphery, excess NGF can lead to peripheral and central sensitization, amplifying pain signaling and heightening the perception of pain.1-5

IS DRIVEN BY EXCESS NGF HERE

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Learn more about how peripheral and central sensitization drive chronic pain at PainDrivers.com References: 1. Pinho-Ribeiro FA, et al. Trends Immunol. 2017;38:5-19. 2. Latremoliere A, Woolf CJ. J Pain. 2009;10:895-926. 3. McGreevy K, et al. Eur J Pain Suppl. 2011;5:365-372. 4. Mantyh PW, et al. Anesthesiology. 2011;115:189-204. 5. Chang DS, et al. J Pain Res. 2016;9:373-383.

By Mechele Fillman MSN, NP

In 2008, I was a nurse practitioner working as an intensive care unit registered nurse (RN) at a nonprofit, faith-based hospital. Many of the surgical patients were managed postoperatively only with opioids, as opposed to opioid sparing medications and techniques.1 My previous position was at a large university hospital where epidurals were used frequently for postoperative pain management, so I was frustrated with this lack of interventional pain management options. So I did what any self-respecting patient advocate would do: I complained. To surgeons, to the anesthesiologists, to the hospital administrators, to anyone who would listen. Administration then asked me to do something about it. [Be careful what you complain about!] This started my journey in search of literature to guide setting up an inpatient acute pain service. At that time, information was difficult to come by. I persevered and was able to establish and manage an acute pain service for 4 years before being recruited to a university hospital. There I was asked to help grow their existing inpatient pain service. After working there 6 years, I was recruited by a smaller community hospital to start a pain service from the beginning. Despite the hard work and difficulties, I agreed to start all over again, simply because it was so needed. advanced practice provider

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Q 4 | 2019

There are no clear guidelines for developing an inpatient acute pain service.2 Nor are there any guidelines to help determine the mix of services. Should it be regional anesthesia based only or just acute pain patients or a mix of acute and chronic pain patients. Who runs it? Anesthesia? Hospitalist? Advanced practice provider? Dedicated hospital based pain services are uncommon except in large academic centers. What would motivate a smaller hospital to start a new service line? For one thing, the opioid crisis, where opioids are intermittently in limited supply, and frequently overprescribed. There is a national cry for more appropriate opioid prescribing and limiting the number of pills given at any one time. Secondly, the Joint Commission lists 16 requirements surrounding pain, and states that “The hospital provides information to staff and licensed independent practitioners on available services for consultation and referral of patients with complex pain management needs.”3 The rationale for the fulfillment of this requirement is “Access to pain specialists by consultation or referral reflecting best practice in managing patients with complex pain management needs.”3 To that end, hospitals are encouraging opioid sparing strategies that require expertise in postoperative pain management, which is sometimes complicated by substance abuse and/or chronic pain with opioid tolerance.

Starting an acute pain service involves many steps, the first of which is to gain administrative support.4 Without it, moving forward and sustaining the service will be difficult, if not impossible. One way to gain support is to show those in charge the potential for saving money and increasing patient satisfaction. At my previous hospital, I was working at the bedside when the Chief Operating Officer (COO) was spending side-byside time with the staff and, on this particular day, me. Two patients in the intensive care unit had had the same surgery. One patient did not have an epidural and was postoperative day 4 in the unit; the second patient had an epidural. The second patient was awake and alert, able to meet postoperative goals, including getting out of bed and using the incentive spirometer, and left the unit postoperative day 2. The first patient kept repeating “I want to die.” Those real life examples painted a very dramatic picture for the COO of how postoperative pain management has the potential to decrease spending and increase patient satisfaction. In my years as an inpatient Q 4 | 2019

pain expert, I have heard many joint replacement patients state that when they had their first hip or knee “done” years before it was an awful experience, but the second time they reported being almost pain free, able to work with physical therapy and go home earlier than they had the first time. This was due, in part, to their being at a hospital that offered the interventional and updated pain management strategies that an acute pain service can provide.

When attempting to set up an acute pain service, having a dedicated champion is extremely helpful. With core practice competencies that include independent practice, practice accountability, and leadership skills, advanced practice providers (APPs) are uniquely positioned to be that champion.5 APPs with these competencies are able to see patients with little or no oversight, which can contribute to the efficiency and cost savings of any acute pain service. Decision-making and responsibility for the acute pain service in total—patients, policies, and staff—requires strong leadership ability to navigate the direction of a growing pain service. The champion could also be any staff member with the drive, passion, and commitment to oversee the start-up. When the pain service began to grow, we looked for staff who were not deterred by challenging patients and situations, who wanted to know more about pain and solve the pain management puzzle. Without that drive and passion, burnout will be inevitable.

After identifying a champion, the next order of business is developing a plan.6 It can be in the form of a team charter that identifies the administrative sponsor and team leaders. Other items to include in a charter: purpose/mission statement, goals, and scope and responsibilities of the pain service. For example, a purpose could be “To provide a comprehensive, multidisciplinary, integrated system-wide approach to pain management that ensures safety and mitigates side effects while reducing pain for patients with acute and chronic pain.” Goals may include: provide a system-wide standard of care for pain management that reduces suffering from preventable pain while emphasizing safety; ensure that pain assessment is performed in a consistent manner; and ensure that pain treatment is www.painweek.org | PWJ

Starting an acute pain service involves many steps, the first of which is to gain administrative support.4

prompt and appropriate.7 Goals will likely mirror Joint Commission requirements.3 Scope will depend on resources and the experience of the available staff. For my first pain service we developed quite a broad scope: “All patients requiring advanced pain intervention and consultation in the hospital.” Citing responsibilities will again depend on resources and the experience of staff, but could include development of policies and procedures (of note, at larger university hospitals, the pain service’s members usually act as content experts for policies and procedures); performance of daily rounds and charting on pain service patients; providing pain management educational opportunities; and any other responsibilities that would be necessary for the smooth day-to-day operations of the service. If the institution has a performance improvement or organizational development department available, enlisting their expertise can be invaluable for bringing the stakeholders to the table, bringing up items that may have been overlooked, and helping with team building. Organizing and staffing an acute pain service will be dependent on the resources available, but minimally should include an anesthesiologist and a nurse advocate and, ideally as mentioned above, an APP. Choice of model, ie, APP lead with anesthesia support, will depend on availability, commitment, and the experience of staff interested in building an acute pain service. Other staff could include: a pain psychologist, a pharmacist, a physical therapist, an occupational therapist, a palliative care provider, and a pastoral care provider, or more than one of each if needed. If an RN is to be part of the team, ensure that there are protocols in place which will allow them to stay within their scope of practice.

In addition to staffing, identifying stakeholders will help support and sustain a pain service. Surgeons, nurse educators, nurses, hospitalists, and finance personnel should be identified as stakeholders even though they may not be involved in the daily running of the acute pain service. Anesthesiologists not directly concerned with the acute pain service should be considered stakeholders and part of coverage decisions.

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Advertising the exact contact information for the acute pain service will allow providers to easily place consults. Confusion and frustration often arise when providers do not have the correct contact information and call different or wrong numbers. There should be a dedicated phone line that can be forwarded to individual phones or a pager. A public on-call list is a familiar way for nurses and providers alike to know who is on call and how to reach that staff member. Pain certification is available for RNs and should be encouraged. Physicians have their own pain management certification or regional anesthesia certification. Currently, no APP certification in pain management exists. Careful documentation, from the mentoring physician as well as pain management continuing education units, should be maintained. Reaching out to a pain management expert to evaluate the pain service program and provide recommendations can help to boost the validity of a new service line. During my first start-up, I discovered that the university hospital had an inpatient pain service led by an APP. I connected with the lead who, in turn, made recommendations for pain management organizations with resources to guide me. The American Society for Pain Management Nursing (www. aspmn.org) is a very important foundation resource for RNs and APPs. Also, the American Academy of Pain Medicine (painmed. org) offers resources and conferences. Both of these organizations are excellent places to start and ways to encounter the leading experts in the field. PAINWeek (www.painweek.org) is a yearly, week-long conference that offers lectures and access to pain experts and industry professionals.

Administrative work is tedious but necessary. Hospital credentialing will need to be approved and maintained. Prescription monitoring program access is essential for all members of the team who qualify. Many states require and monitor how often this program is accessed. Job descriptions must be established. Policies and protocols for any new interventions should be guided by, if not written by, the new pain service. The APP should work with institutional nurse educators to establish maintenance and documentation of competencies for new protocols and procedures. Q 4 | 2019

Without it, moving forward and sustaining the service will be difficult, if not impossible. Enlist the help of the finance director to establish billing codes and an avenue to bill. In the event the ability to bill for the APP is not established, keep track of all patients seen, either via an electronic record or a spreadsheet. Readdress billing periodically to capture as much revenue as possible. Services provided by the acute pain service will depend on the size and need of the institution as well as the experience of the staff. The hours of the acute pain service for consultation, and how patients will be covered after hours, must be put in place.

When considering what services to offer, think about the following: ○○ Will the acute pain service consult on surgical/ acute pain patients only? ○○ Will the acute pain service consult on chronic pain patients with acute flare? ○○ Will the acute pain service consult on chronic pain patients who have been admitted? ○○ Will the acute pain service manage all patient controlled analgesia pumps? ○○ Will the acute pain service manage all epidurals and nerve catheters or split the responsibility with the regional service (if one exists)? ○○ Will the acute pain service write the pain orders or write only recommendations? ○○ Will patients be seen in the emergency department or in the psychiatry unit if consulted? ○○ How will palliative care patients who have had surgery or been admitted to the hospital be seen? Offering only 1 or 2 services can make for a more manageable start-up. Adding more as the service line grows and matures will be an avenue of sustainability.6 Q 4 | 2019

Helping with education through continuing education credit lectures or shorter lunch and learns will solidify pain management protocols and procedures. Education ensures everyone is on the same pain management page and provides a more consistent experience for the patient.

Committed administrative support is imperative for starting and sustaining an acute pain service. Make a solid plan with committed staff. Do not skimp on administrative work, and ensure that all certifications, licensure, and credentialing are in place. Work with finance to capture appropriate billing. Provide services that fit the experience and availability of the staff. Commitment and passion will break through barriers and allow for a successful acute pain service start-up. While there is no lack of frustration when starting an acute pain service, it takes only a well pain-managed patient or a relieved hospitalist or nurse to make it worth doing all over again. References 1. Said ET, Sztain JF, Abramson WB, et al. A dedicated acute pain service is associated with reduced postoperative opioid requirements in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Anesth Analg. 2018;127(4):1044–1050. 2. Mariano E. Starting a new regional anesthesia program. Available at: www. edmariano.com/?s=starting+a+new+regional+anesthesia+program. 3. The Joint Commission. The Joint Commission enhances pain assessment and management requirements for accredited hospitals. LD.04.03.13 EP3. The Joint Commission Perspectives. 2017;37:1–4. Available at: www.jointcommission.org/assets/1/18/ Joint_Commission_Enhances_Pain_Assessment_and_Management_Requirements_for_ Accredited_Hospitals1.PDF. 4. Schwenk ES, Baratta JL, Gandhi K, et al. Setting up an acute pain management service. Anesthesiol Clin. 2014;32(4):893–910. 5. Thomas A, Crabtree MK, Delaney K, et al. The National Organization of Nurse Practitioner Faculties. Nurse practitioner core competencies. 2014. Available at: https://cdn.ymaws.com/www.nonpf.org/resource/resmgr/competencies/2014npcorecompscontentfinaln.pdf. 6. Anderson CTM. The hardware of a functional acute pain service. Pediatric Anesthesiology. February 23–26, 2012. Session 6: Workshop. Available at: Pedsregional.net. 7. Kerns RD, Phillip EJ, Lee AW, et al. Implementation of the Veteran’s Health Administration National Pain Management Strategy. Transl Behav Med. 2011;1(4):635–643.

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By Jorge Carrillo MD / Georgine Lamvu MD, MPH

By Jorge Carrillo MD, facog / Georgine Lamvu MD, MPH

Chronic pelvic pain (CPP) is defined as noncyclic pain of

≥6 months’ duration that localizes to the anatomic pelvis, anterior abdominal wall at or below the umbilicus, the lumbosacral back or the buttocks, and is of sufficient severity to cause functional disability or lead to medical care.1 The prevalence of CPP is thought to range between 2.1% and 26.6%2,3 among women and from 2% to 9.7% among men.4,5 Almost 23 million women in the US suffer from CPP; it accounts for up to 10% of outpatient gynecologic consults and nearly 58,000 hysterectomies are performed annually due to this condition. The economic burden of CPP on the US healthcare system is estimated at 2 billion dollars annually.6 -8 There is evidence that applying a biopsychosocial model to treat chronic pain can positively impact patients and treatment outcomes.9-14 This model focuses on both disease and illness, disease being defined as an “objective biological event involving the disruption of specific body structures or organ systems caused by either anatomical, pathological, or physiological changes,”9 representing the biocomponent of the model, and illness being “a subjective experience or self-attribution that a disease is present,”9 the psychosocial component of the model. Healthcare providers are usually trained to approach patients from the biological-disease component, often not addressing the psychosocial-illness component. Furthermore, addressing the psychosocial illness component requires extensive patient involvement and education. pelvic pain

This year the US Department of Health and Human

What is pain?

Services (DHHS) released a document titled “Pain Management Best Practices Inter-Agency Task Force Report. Updates, Gaps, Inconsistencies, and Recommendations.”15 The document is intended to guide federal agencies, private stakeholders, and the public at large through common gaps identified in the treatment of pain patients. The recommendations encourage providers, policymakers, legislators, regulators, and patients to adopt a biopsychosocial approach to pain management. Education is identified as a key component of any best practice model, and the report emphasizes the importance of providing patients with opportunities to better understand their disease process as well as interactions between pain, pain triggers, the body, and the mind. The DHHS task force identified gaps in knowledge:

In August of 2019 the International Association for the Study of Pain (IASP)20 proposed a new definition for pain as an “aversive sensory and emotional experience typically caused by, or resembling that caused by, actual or potential tissue injury” with the following proposed accompanying notes:

○○ Patient education is lacking for both acute and chronic pain. ○○ Patient expectations for pain management in the perioperative time period are frequently not aligned with surgical practices or procedures that require pain management. ○○ Educational materials and interventions for patients with chronic pain lack consistency, standardization, and comprehensive information.15 ○○ Patient education about pain is important because of its impact on clinical outcomes.16-18 Changing patient knowledge and beliefs about pain can improve self-management of pain. A recent study found that patients who participate in pain education and reported a shift in their pain cognition or self-management strategies, had lower perceived pain and higher expectations of recovery than those who were educated but did not experience changes in pain cognition or self-management.19

Q 4 | 2019

○○ Pain is always a subjective experience that is influenced to varying degrees by biological, psychological, and social factors. ○○ Pain and nociception are different phenomena: the experience of pain cannot be reduced to activity in sensory pathways. ○○ Through their life experiences, individuals learn the concept of pain and its applications. ○○ A person’s report of an experience as pain should be accepted as such and respected. ○○ Although pain usually serves an adaptive role, it may have adverse effects on function and social and psychological well-being. ○○ Verbal description is only one of several behaviors to express pain; inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain. It is important to educate the patients about this definition which emphasizes that pain is an emotional experience that is learned, and related to life experiences or events, making it unique to each individual. This definition also implies that there is a link between cognition and pain perception. Cognition and influence of beliefs/appraisal on pain perception A classic experiment conducted by Arntz and Claassens21 describes the relationship between cognition and pain. In their experiment, 31 healthy students were told that they would be exposed to either a hot or cold stimulus after which they would be asked to report their pain level. In the experiments, all participants were only exposed to a cold stimulus. When they were asked to report pain scores, the participants who thought that they were exposed to a hot stimulus reported higher levels of pain than the ones who thought that they were exposed to a cold stimulus. The researchers showed that the participants reported their discomfort based on what they believed they were exposed to, regardless of the actual exposure, which was always cold, www.painweek.org | PWJ

because heat is considered to be more tissue-damaging than cold. This helped reinforce the hypothesis that the experience of pain is influenced by what tissue damage means (or represents) to an individual, and that the understanding of pain is a complex interplay between beliefs, expectations, and interpretation.21 Pain appraisal and pain belief are factors that influence pain cognition. Pain appraisal refers to the meaning of pain by an individual (threatening, benign, or irrelevant), and pain beliefs develop during a lifetime and are a result of learning history, covering all aspects of pain experience (causes, prognosis, treatments). In the end, pain beliefs can shape pain appraisals,9 both factors impact the affective and behavioral response to pain and are thought to also influence the adjustment to chronic pain. Specifically, some beliefs have been associated with maladaptive responses to chronic pain,9 such as:

○○ Pain is a signal of damage ○○ Activity should be avoided when one has pain ○○ Pain leads to disability ○○ Pain is uncontrollable ○○ Pain is a permanent condition Providers could potentially help the patient change these maladaptive responses by reconceptualizing chronic pain as less threatening by shifting the following beliefs: that pain is not a measure of the state of the tissues; that pain is modulated by many factors, from somatic, psychological, and social domains; that the relationship between pain and the state of the tissue becomes less predictable as pain persists; and that pain can be conceptualized as a conscious correlate of the implicit perception that tissue is in danger.22

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Additional complexities of pain localized to the pelvis In the case of CPP, there are additional factors to consider. First, although somatic, 1) neurologic and visceral structures converge in the pelvis, 2) psychological processing of visceral pain differs from somatic pain, and 3) clinically visceral pain differs from somatic pain in several aspects. For example, visceral pain23-27

○○ Is not evoked from all viscera ○○ Is not always linked to visceral injury— it can arise from hollow organ distension, stretching, traction on mesentery, organ hypoxia/ischemia, chemical stimuli23 ○○ Is clinically described as being diffuse and poorly localized and usually refers to other locations ○○ Is accompanied with motor and autonomic reflexes (such as nausea and low back muscle tension) ○○ Is often intermittent in nature with acute episodes of intense pain Additionally, some neurophysiological phenomena are particular to visceral structures, such as viscerosomatic conversion, a phenomenon in which a noxious stimulation of the viscera triggers pain in the somatic site with the corresponding dermatome. For example: ovarian pain can be felt in the distribution of the iliohypogastric nerve or T12–L1 dermatome, or uterine pain can be felt in the distribution of the lateral femoral cutaneous nerve or L2–3 dermatomes, whereas the lower uterus, cervix bladder, distal ureter, upper vagina, and rectum can result in pain along the distribution of the pudendal nerve or S2–4 dermatomes.28,29 Q 4 | 2019

…concepts are introduced to impact patients’ beliefs, attitudes, behaviors, treatment, and lifestyle choices… avoiding words and phrases like tear, deterioration, herniation… Using metaphors, examples, and pictures…

Another example of the complexity found within the abdominopelvic structures is a viscerovisceral convergence or “visceral cross-sensitization” phenomena, in which gastrointestinal, genitourinary, and reproductive organs “communicate” and transmit noxious stimulus from the diseased pelvic organ to adjacent normal structures, leading to functional changes. This can occur via both peripheral and central mechanisms leading to central sensitization and visceral hyperalgesia.23,28,30 The first paper looking into the effect of neuroscience education for women with chronic pelvic pain was published by James et al in 2019. This study developed an educational program that combined the specific and unique features of female CPP with a widely used general pain education format—Explain Pain. Women with CPP were exposed to this educational format through a 90-minute seminar followed by a period of discussion where participants could ask questions. The main outcome of the study was to assess general pain knowledge, and changes in perception about the reasons for the onset and persistence of pelvic pain. A total of 25 women with multiple CPP conditions (endometriosis, bladder pain syndrome, genitopelvic pain/penetration disorder) completed the initial questionnaire (assessing knowledge), and 21 answered 3 open-ended questions (assessing depth in knowledge/understanding questions). There was a significant improvement in pain knowledge in all patients, and for almost 40% of the 21, there was an improved depth in knowledge.31 It is important for providers treating patients with CPP to educate patients not only about what is pain and the cognitive factors associated with its perception, but also about how visceral pain differs from somatic and neuropathic pain in the pelvis. Q 4 | 2019

If we understand that pain is at least in part cognitively mediated, then we can expect that modifying cognition—the beliefs and appraisal around pain—may lead to improvements in the pain experience. However, modifying pain beliefs and appraisal can be challenging. In the education field, it is well known that learning is the result of the interaction between the prior knowledge of a learner, and the concept or ideas that are presented to be learned. However, existing knowledge is frequently contradictory to the new information presented, creating an obstacle to the learning process, resulting in the need for conceptual change or reconceptualization.32 These challenges are also present in the clinical world. Often patients interpret pain as a state of danger to body tissue with a reflective need of protective behavior, and while this is applicable to some conditions linked to painful sensations, this is not always the case in chronic pain. Traditional educational approaches use anatomical, biomechanical, or pathological models to explain pain, but these carry an inability to explain persistent pain, peripheral and central sensitization, facilitation and inhibition, neuroplasticity, spreading pain, allodynia, pain in absence of injury or disease, immune responses or stress biology, and is often associated with inducing fear, anxiety, and faulty beliefs, which can negatively impact the pain experience.16,33 As a result, different educational approaches— Explain Pain, pain biology education, pain neuroscience education—have been developed to explain chronic pain from a biological and psychological perspective.33 The main goal of these educational methods is to change someone’s understanding of what pain is, what function it serves, and the biological processes that surround it. Conceptual change is applied and important topics that are taught to pain www.painweek.org | PWJ

pelvic pain

sufferers include “the variable relationship between nociception and pain, the influence of context in pain, upregulation of the nociceptive system as pain persists, the coexistence of multiple potential protective systems (pain being one), the influence of these protective systems on pain, the adaptability and trainability of our biology and the knowledge that this adaptation back to normality is likely to be slow.”17 All these concepts are introduced to impact patients’ beliefs, attitudes, behaviors, treatment, and lifestyle choices when associated with pain. Ideally this should be done using nonthreatening language, avoiding words and phrases like tear, deterioration, herniation, wear and tear, degeneration, which increase fear and anxiety.33 Using metaphors, examples, and pictures (for example, the metaphor of the nervous system being an alarm system that initially turns on due to a stimulus, but that could become extra sensitive leading to altered perceptions) are useful and found to be effective. These kinds of metaphors allow the clinician to discuss not only issues surrounding the initial injuries causing pain, but also failed treatments, stress, and anxiety. Some research studies suggest this patient educational model can take up to 4 hours in some settings, whereas other researchers have shown that it can be delivered in small 10 to 20 minute sessions, depending on each patient’s needs.33,34 It has been presented in different formats since it was first described in 2002, such as 1-to-1, small group tutorial sessions, large group seminars, books or booklets, storybooks, and online videos.17,33,35,36 There are multiple randomized controlled studies looking at the impact of this educational approach in clinical conditions including low back pain, lumbar radiculopathy, fibromyalgia, chronic fatigue syndrome, whiplash, general chronic pain, and, despite the heterogeneity of these studies, most of them revealed a positive effect in knowledge of pain, decreasing pain, increasing physical performance, decreasing perceived disability, and decreasing catastrophization.17,18,37,38 However, a 2008 Cochrane review stated there is only low-level evidence for this educational approach in improving short-term pain and function.37 A more recent systematic review by Louw et al analyzed the efficacy of pain neuroscience education on musculoskeletal pain.16 In this study the primary outcomes were pain, function, psychosocial factors, movement, and healthcare utilization. The review included 13 published papers with 734 subjects of which 398 received this educational model for different conditions including low back pain, chronic fatigue syndrome, fibromyalgia, lumbar radiculopathy awaiting surgery, and chronic neck pain. The follow-up period varied from immediate post-intervention to 1 year. The authors concluded that there was improvement in pain ratings, pain knowledge, disability, pain catastrophization, fear-avoidance, attitudes and behaviors regarding pain, physical movement, and healthcare utilization. A very important finding was that of the 13 studies evaluated, 5 had this educational format alone and did not show a decrease in pain ratings, and in the 5 studies in which it was combined with physical intervention (physical therapy),

42 PWJ | www.painweek.org

the pain was significantly reduced, leading to the hypothesis that education alone is not sufficient to achieve a change.16

Conclusion Educating patients about pain has been identified as an important starting point in treating chronic pain patients. Early research shows that similar educational approaches are also beneficial in women with chronic pelvic pain. When teaching patients about pain, it is important to discuss the definition of pain, its pathophysiology, the relationship between pain and cognition, and, for chronic pelvic pain patients, the complexity of the abdominopelvic visceral system. Current evidence suggests that pain education should not be used alone16,38 but rather as part of multimodal treatment, and that this combination can have a positive impact in pain perception, interpretation, and clinical outcomes. References 1. ACOG Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 51. Chronic pelvic pain. Obstet Gynecol. 2004;103(3):589–605. 2. Latthe P, Latthe M, Say L, et al. WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health. 2006;6(6):177. 3. Ahangari A. Prevalence of chronic pelvic pain among women: an updated review. Pain Physician. 2014;17(2):E141–147. 4. Krieger JN, Lee SWH, Jeon J, et al. Epidemiology of prostatitis. Int J Antimicrob Agents. 2008;31(suppl 1):S85–90. 5. Ku JH, Kim SW, Paick JS. Epidemiologic risk factors for chronic prostatitis. Int J Androl. 2005;28(6):317–327. 6. Yunker A, Sathe NA, Reynolds WS, et al. Systematic review of therapies for noncyclic chronic pelvic pain in women. Obstet Gynecol Surv. 2012;67(7):417–425. 7. Zondervan K, Barlow DH. Epidemiology of chronic pelvic pain. Baillieres Best Pract Clin Obs Gynaecol. 2000;14(3):403–414. 8. Speer LM, Muskbar S, Erbele T. Chronic pelvic pain in women. Am Fam Physician. 2016;93(5):380–387. 9. Gatchel RJ, Peng YB, Peters ML, et al. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull. 2007;133(4):581–624. 10. Kamper SJ, Apeldoorn AT, Chiarotto A, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and metaanalysis. BMJ. 2015 Feb 18;350:h444. 11. Cheatle MD. Biopsychosocial approach to assessing and managing patients with chronic pain. Med Clin North Am. 2016;100(1):43–53. 12. Meints SM, Edwards RR. Evaluating psychosocial contributions to chronic pain outcomes. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87(Pt B):168–182. 13. Williams AC, Craig KD. Updating the definition of pain. Pain. 2016;157(11):2420–2423. 14. Kamper SJ, Apeldoorn AT, Chiarotto A, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain. Cochrane Database Syst Rev. 2014 Sep 2;(9):CD000963. 15. HHS Office of the Assistant Secretary for Health. Report on pain management best practices: updates, gaps, inconsistencies, and recommendations. 2019. Available at: www.hhs.gov/ash/advisory-committees/pain/reports/index.html.

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16. Louw A, Zimney K, Puentedura EJ, et al. The efficacy of pain neuroscience education on musculoskeletal pain: a systematic review of the literature. Physiother Theory Pract. 2016;32(5):332–355. 17. Moseley GL, Butler DS. Fifteen years of explaining pain: the past, present, and future. J Pain. 2015;16(9):807–813. 18. Louw A, Diener I, Butler DS, et al. The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Arch Phys Med Rehabil. 201192(12):2041–2056. 19. Mittinty MM, Vanlint S, Stocks N, et al. Exploring effect of pain education on chronic pain patients’ expectation of recovery and pain intensity. Scand J Pain. 2018;18(2):211–219. 20. International Association for the Study of Pain. IASP’s proposed new definition of pain released for comment. August 7, 2019. Available at: www.iasp-pain.org/ PublicationsNews/NewsDetail.aspx?ItemNumber=9218&navItemNumber=643. 21. Arntz A, Claassens L. The meaning of pain influences its experienced intensity. Pain. 2004;109(1–2):20–25. 22. Moseley GL. Reconceptualising pain according to modern pain science. Phys Ther Rev. 2007;12:169–178. 23. Gebhart GF, Bielefeldt K. Physiology of visceral pain. Compr Physiol. 2016;6(4):1609–1633. 24. Cervero F. Visceral versus somatic pain: Similarities and differences. Dig Dis. 2009;27(suppl 1):3–10.10. 25. La JH, Gebhart GF. Visceral pain. In: Aminoff M, Daroff R, eds. Encyclopedia of the Neurological Sciences. Waltham, MA: Elsevier Inc; 2014:672–676. 26. Cervero F. Visceral pain - central sensitisation. Gut. 2000;47(suppl 4): iv56-iv57; discussion iv58. 27. Laird JMA, Cervero F. Looking at visceral pain: new vistas. Scand J Pain. 2011;2(3):93–94. Available at: https://www.degruyter.com/view/j/sjpain.2011.2. issue-3/j.sjpain.2011.05.002/j.sjpain.2011.05.002.xml.

28. Sikandar S, Dickenson AH. Visceral pain: the ins and outs, the ups and downs. Curr Opin Support Palliat Care. 2012;6(1):17–26. 29. Perry CP. Peripheral neuropathies and pelvic pain: diagnosis and management. Clin Obstet Gynecol. 2003;46(4):789–796. 30. Origoni M, Leone Roberti Maggiore U, Salvatore S, et al. Neurobiological mechanisms of pelvic pain. Biomed Res Int. 2014;2014:903848. [ePub 2014 Jul 8] 31. James A, Thompson J, Nuemann P, et al. Change in pain knowledge after a neuroscience education seminar for women with chronic pelvic pain. Continence Foundation of Australia. 2019;25(2):39–44. Available at: www.sydneypelvicclinic.com. au/spc-wp/wp-content/uploads/james_et_al-ANZCJ-Vol25_No2_2019_pp39–44.pdf. 32. Troyer JA. Conceptual change instruction: a method for facilitating consciousness in problem solving activities. Procedia Soc Behav Sci. 2011;29:33–38. 33. Louw A, Zimney K, O’Hotto C, et al. The clinical application of teaching people about pain. Physiother Theory Pract. 2016;32(5):385–395. 34. Robinson V, King R, Ryan CG, et al. A qualitative exploration of people’s experiences of pain neurophysiological education for chronic pain: The importance of relevance for the individual. Man Ther. 2016;22:56–61. 35. Moseley L. Combined physiotherapy and education is efficacious for chronic low back pain. Aust J Physiother. 2002;48(4):297–302. 36. Heathcote LC, Pate JW, Park AL, et al. Pain neuroscience education on YouTube. Peer J. 2019;7:e6603. 37. Engers A, Jellema P, Wensing M, et al. Individual patient education for low back pain. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004057. 38. Geneen LJ, Martin DJ, Adams N, et al. Effects of education to facilitate knowledge about chronic pain for adults: a systematic review with meta-analysis. Syst Rev. 2015;1(4):132.

By Jessica Geiger

By Jessica Geiger pharmd, bcps, cpe

how legislation, guidelines, and reimbursement policies impact patient care

I was a kid, I played a game called Don’t Spill the Beans, where players take turns placing a bean on a suspended, balanced container. The person who caused the container to tilt too far and spill the beans, loses the game. (This game—and goal—was the inspiration for my 2019 PAINWeek presentation.) In my mind we, as a society, have been adding more and more anti-opioid beans to the container, some of them carefully placed with noble intent, and some just thrown on top with no thought to potential adverse outcomes. More than 11% of Americans have daily pain; more than 4% have considerable daily pain.1 The cost of chronic pain is approximately $600 billion dollars annually, which is inclusive of medical care and lost productivity.2 The additional “beans”—legislation or insurance rules—are not necessarily helping us solve the pain problem. To understand where we are, we have to understand where we have been. In 1970, the Controlled Substances Act was established.3 It was designed to regulate possession, use, manufacturing, control, and classification of certain controlled substances. This legislation also validated opioid medications as necessary components of pain treatment. Additional legislation changes in the 1980s and 1990s led to fewer restrictions on opioids, and the patients who were experiencing noncancer related pain were able 46 PWJ | www.painweek.org

to have opioids as part of their pain management regimen. By the 1990s, multidisciplinary pain clinics were in existence, but it was difficult to get insurance companies to pay for therapies that were not medications. At the same time, a small paper was published that suggested the risk of addiction was low for patients with chronic noncancer pain.4 A call to action for better pain control was also released in the 1990s, and in 1997 pain was classified as the fifth vital sign. In 2001 the Joint Commission released standards regarding underassessment and undertreatment of pain.5 In 2002 pain was no longer recognized as the fifth vital sign and in 2009 the required pain assessment was removed from Joint Commission standards. Then, in 2016, the Centers for Disease Control and Prevention (CDC) released their guideline for chronic pain.6 The CDC guideline stresses appropriate dosing, treatment duration, and assessment of the risk/ benefit of using opioids. It also includes suggested morphine milligram equivalent (MME) thresholds of 50 and 90 daily. Once a patient surpasses 50 MME, it is suggested that further increases be carefully reassessed and ≥90 MME should be avoided unless there is justification. When treating acute pain, the recommended duration per the guideline was ≤1 week, unless there was justification for a longer duration. The CDC carved out exceptions for hospice and palliative care patients as well as patients with Q 4 | 2019

a cancer diagnosis.7 This guideline was meant to be just that, a guideline. But unfortunately, restrictive legislation and insurance rules followed closely. The problem we are now facing is that legislation has been implemented based on the guideline that makes it exceedingly difficult for physicians and other prescribers to adequately care for patients, regardless of whether they fall under the exceptions. Many states have implemented a maximum morphine equivalent daily dose, or MEDD, and day supply limits. Lawmakers either don’t understand or have ignored the fact that MEDD is based on equivalent efficacy, not toxicity, and that such comparisons do not consider individual patient characteristics. Insurance companies added an extra layer of complication by using the guideline as a hard stop for requiring prior authorizations or simply refusing to pay. Unintended consequences of the legislation and insurance rules have resulted in delays in patient care, disruptions in treatment plans, and increased provider workload—having to justify to insurance companies why certain medications are the most appropriate. An example of a delay in care is a patient who was a great self-advocate and participated in many conversations, and made phone calls for an appointment with a pain specialist for outpatient management. Her appointment was scheduled for 10 days after discharge. The palliative service had signed off because a great plan was in place, and it Q 4 | 2019

appeared everyone was on board with continuing this plan at discharge. However, at that time, the discharging hospitalist would write an opioid prescription for only 7 days. Imagine how that patient must have felt knowing she would run out of medication 3 days before her appointment. This is a story that happens all too often. A study by Bohnert and colleagues analyzed national trends on opioid prescribing after implementation of the CDC guideline.8 After its publication, sharp declines were seen in both prescribing rates and high dose (>90 MME) opioid prescribing. What wasn’t addressed in the paper was the reason why these rates declined: Was it better patient care? Better assessment? Or not? State level data are also available. Florida, Indiana, Kentucky, and West Virginia have all published papers on the impact of opioid specific legislation.9-11 All 4 states allow exceptions for certain patients (ie, palliative care, hospice, cancer diagnosis), but physicians writing prescriptions may not be comfortable utilizing such exceptions, feeling as if a DEA target is painted on their backs. The end result? Patients are frequently sent home with a fraction of what they need in either number of tablets/capsules or overall dosage. In Florida, the HB-21 bill was passed that implemented restrictions on prescription duration for acute pain.10,12 www.painweek.org | PWJ

The research focused on the impact of HB-21 on prescribing patterns. Results showed a 21% decrease in opioid prescriptions in the 6-month period after passage of HB-21. Legislation in Indiana has been implemented regarding emergency prescribing rules, and the impact of these rules was studied.13 Results included a decrease in prescribed morphine equivalent dose (MED), fewer prescriptions written after implementation, and a decrease in higher MED prescriptions. A study in Kentucky and West Virginia evaluated the direct and indirect impact of opioid related legislation.10 Direct impacts included increased naloxone access, pharmacist delivery of medication assisted treatment for substance use disorder, and required sale/dispensing of an opioid disposal kit. Indirect impacts included prescription drug monitoring system data sharing, increased education, and treatment program oversight. An additional unique component of this paper was that criminal activity was transmitted to the prescription drug monitoring program so that it could be evaluated alongside medication utilization. A small study in Indiana evaluated patient experience.13 A group of 9 patients who were seen in a pain management clinic were surveyed to understand the impact of opioid specific legislation from a patient perspective. Pain management for these patients was disrupted by regimen changes, new vetting processes that delayed care, and a lack of care coordination. Patients also felt there was a shift in the power dynamic, as though they were no longer part of the care team, which resulted in decreased trust in their physician. Patients were also affected by abrupt tapers, sudden discontinuation of a therapy that had been working, loss of providers, and dose limits. Information on the impact of legislation is not limited to research studies and has reached mainstream media. The New York Times published an article that addressed fear among patients about opioid use.14 The patient in the article had medical conditions that caused severe pain, but he/she was afraid to use the prescribed opioids. Science published an article that brought to life how patients are feeling in response to opioid specific legislations.15 Patients in whom it is appropriate to use opioids are feeling criminalized. A final impact of opioid legislation is an increase in suicide rates. A study published in October 2018 evaluated the effect of chronic pain on suicide rates.16 From 2003 to 2014, >120,000 suicide deaths were identified; in >10,000 of those deaths, there was evidence of chronic pain. Suicides with chronic pain increased from 7.4% in previous reports to 10.2% in the current report. The data for this study came from 48 PWJ | www.painweek.org

the National Violent Death Reporting System, which links data on violent deaths from death certificates, coroner reports, and law enforcement reports.16 What can we do about this? First and foremost, we can keep the patient at the center of our care. We can advocate on his/her behalf with insurance companies and other providers and collaborate. Additionally, we must write letters to legislators to advocate for better pain management and bring light to anything incorrect that we may come across in published information. References 1. Nahin RL. Estimates of pain prevalence and severity in adults: United States. J Pain. 2015;16:769–780. 2. Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13:715–724. 3. Sacco LN. Drug enforcement in the United States: history, policy and trends. Congressional Research Service. 2014. Available at: https://fas.org/sgp/crs/misc/ R43749.pdf. 4. Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. 1980;302:123. 5. Baker DW. The Joint Commission’s pain standards: origins and evolution. Oakbrook Terrace, IL: The Joint Commission. 2017. 6. Bernard SA, Chelminski PR, Ives TJ, et al. Management of pain in the United States – a brief history and implications for the opioid epidemic. Health Serv Insights. 2018 Dec 26;11:1178632918819440. 7. Dowell D, Haegerich T, Chou R. No shortcuts to safer opioid prescribing. N Engl J Med. 2019;380:2285–2287. 8. Bohnert A, Guy GP, Losby JL. Opioid prescribing in the United States before and after the Centers for Disease Control and Prevention’s 2016 Opioid Guideline. Ann Intern Med. 2018;169:367–375. 9. Potnuru P, Dudaryk R, Gebhard RE, et al. Opioid prescriptions for acute pain after outpatient surgery at a large public university-affiliated hospital: impact of state legislation in Florida. Surgery. 2019;166(3):375–379. 10. Costich JF, Quesinberry D. Opioid-related legislation in Kentucky and West Virginia: assessing policy impact. J Law Med Ethics. 2019;47(S2):36–38. 11. Achkar MA, Grannis A, Revere D, et al. The effects of state rules on opioid prescribing in Indiana. BMC Health Serv Res. 2018;18:1–7. 12. The Florida Senate. CS/CS/HB 21—Controlled Substances. Available at: www. flsenate.gov/Committees/BillSummaries/2018/html/1799. 13. Achkar MA, Revere D, Dennis B, et al. Exploring perceptions and experiences of patients who have chronic pain as state prescription opioid policies change: a qualitative study in Indiana. BMJ Open. 2017;7(11):e015083. 14. Sekeres MA. When patients need opioids to ease the pain. New York Times. 2019. Available at: www.nytimes.com/2019/07/10/well/live/when-patients-need-opioids-toease-the-pain.html. 15. Marill MC. The unseen victims of the opioid crisis are starting to rebel. Science. 2019. Available at: www.wired.com/story/the-true-victims-of-the-opioid-crisis-arestarting-to-rebel. 16. Petrosky E, Harpaz R, Fowler K. Chronic pain among suicide decedents, 2003–2014: findings from the national violent death reporting system. Ann Intern Med. 2018;169:448-455.

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“Meetings come to an end, but learning never stops. PWJ keeps you going all year long.” — Michael R. Clark Md, Mph, Mba

This series is intended to give people exposure to resources that cover the “basics,” so they will then be better able to build on and harvest more knowledge pertinent to their clinical setting and practice.

By Kevin Zacharoff MD, FACIP, FACPE, FAAP

the basics of pain treatment P1 By Kevin Zacharoff MD, FACIP, FACPE, FAAP

“Cure sometimes, treat often, comfort always” —Hippocrates

Introduction

Pain resources often target audiences who already have some degree of foundational knowledge or education. This series is intended to give people exposure to resources that cover the “basics,” so they will then be better able to build on and harvest more knowledge pertinent to their clinical setting and practice.

Pain is a phenomenon that all people encounter at some point in their lives. Both sensory and emotional, pain is defined as being an unpleasant experience associated with actual or potential tissue damage. Pain, in both its acute and chronic manifestations, can commandeer a patient’s body and mind. When improperly managed, pain can lead to decreased productivity and diminished quality of life.1 The consequences of inadequate attention to pain reach into the professional, family, sexual, and vocational realms. Although in many situations pain may not be curable, it is a treatable condition. As the science of pain continues to unravel the mystery of its mechanisms, healthcare providers have an increasingly large arsenal of tools to deploy against pain. There are clinically accepted methods and guidelines for assessing and treating pain in adult, pediatric, and elderly populations. Each measure is calibrated to elicit the most accurate self-report from patients of certain age groups and levels of cognitive ability. In addition, a review of a patient’s medical history and a thorough physical and neurologic examination can be useful in qualifying and quantifying pain.2 Using these measurement tools, a healthcare provider is empowered to treat pain with pharmacologic, nonpharmacologic, and psychological remedies. Treatment should be tailored to the type of pain, the location of the pain, its duration, and its intensity. Other considerations include, but are not limited to, the patient’s medical history and previous reactions to particular drugs. Assessment of the psychological and social consequences of pain is an important part of tailoring treatment. Multimodal treatment strategies are often necessary to achieve success. Any pain treatment needs to be fine-tuned to a patient’s particular needs. There is almost invariably a trial-and-error period while the regimen is adjusted. It is also essential that the patient and his/her family understand the limitations of 52 PWJ | www.painweek.org

pain management. Modern society has high expectations for healthcare, and it is important to communicate that complete relief from chronic pain is frequently not possible. Special considerations apply in cases of young patients, those who are cognitively impaired, those with psychiatric comorbidities, and patients at the end of life. In managing pain, the emphasis should be on effectively minimizing discomfort and maximizing function, while attending to its underlying cause. When treating pain, regardless of the modalities used, some basic pearls of wisdom are worth keeping in mind (Table 1).

Key components of a logical approach to managing pain

Despite the fact that principles and tools exist for assessment and treatment of pain today, barriers also exist that may hinder successful outcomes. Improved education about appropriate assessment and treatment of pain will, it is hoped, someday conquer some of these barriers and the myths they promote. Certainly, an important part of the process of effectively treating pain is to take a logical approach towards assessment and management. Here is a potential model of this kind of approach: ○○ Take a detailed history and perform a physical It is imperative for this critical step, not only to fact find, but also to begin cementing a relationship that has the potential to make, or break, the successful treatment of pain. The clinician needs to establish the hallmark of an effective dialogue: trust and compassion for the patient’s pain. This step also provides the opportunity for the clinician to listen and understand how to explore the impact of pain on the patient’s life. Q 4 | 2019

Table 1. Basic Pearls of Wisdom for Pain Treatment ▸▸Analgesia should be integrated into a comprehensive patient evaluation and management plan. ▸▸The emotional and cognitive aspects of pain must be recognized and treated. ▸▸There is no reliable way to objectively measure pain. ▸▸Pain is most often undertreated, not overtreated. ▸▸Pain control must be individualized. ▸▸Anticipate rather than react to pain. ▸▸Whenever possible, let the patient control her or his own pain. ▸▸Pain control is often best achieved by rational polypharmacy. ▸▸Pain control often requires a multidisciplinary, team approach. Adapted from Ducharme J. Acute pain and pain control: state of the art. Ann Emerg Med. 2000;35:592–603.

○○ Utilize any appropriate testing that can facilitate diagnosis There may or may not be any testing needed, depending on the signs and symptoms. A clinician may feel that the history and chief complaint point towards the diagnosis of migraine headache, for example, and opt to treat with firstline therapy. On the other hand, for the patient presenting with low back pain of sudden onset and acute nature, the clinician may opt to order radiologic tests of the spine before intervening. ○○ Establish realistic and desired common goals of further treatment and/or evaluation This would be the point where effective evaluation and treatment start to take a unique path. It is critical for the clinician to understand what the patient is looking for in terms of successful treatment, regardless of the painful condition. In some situations, the diagnostic answers might be clear, as in headaches, but the impact on the patient’s life, quality of life, and ability to perform activities of daily living must be identified, documented, and constantly revisited along the continuum of care. ○○ Formulate a treatment plan When treating pain, the clinician and the patient need to act as a team to identify measurable, beneficial hallmarks of therapy. The point of this is valuable in many ways, the most significant being the ability to measure success or failure. All parties should understand what those measures are, and what steps will be taken in the event success is not achieved at one point or another. If the patient understands what the alternative plans Q 4 | 2019

are up front, and that there indeed are alternative plans, they may be much more inclined to be more committed to therapeutic trials. This is also the time when the healthcare provider can detail what everyone’s responsibilities are, from all perspectives, with respect to use of opioids or other controlled substances. This might be treatment agreements, periodic testing, and other risk management strategies. ○○ Recognize the flexibility in modification of treatment based on periodic assessment and patient questioning A patient may become unstable in their pain treatment (ie, experience periods of breakthrough pain) and require add-on therapy for a short period of time or even rotation to a different form of drug or modality. Periodic reassessment is necessary to monitor progress, regression, patient compliance, and even exit strategies when opioids are employed. ○○ Refer to a pain specialist The point at which a primary care clinician may opt to refer the patient to a specialist for treatment will vary based on experience, expertise, and comfort level with the medications and modalities necessary for treatment. A specialist may be able to use a more technically complex approach to pain management by attempting to modify the mechanism responsible for the pain. This might be beyond the scope of a primary care provider. The most successful dynamic between the primary care clinician and the pain specialist is when a treatment plan is formulated and implemented by the consultant, and information is communicated between the two clinicians. www.painweek.org | PWJ

Table 2. Common Myths About Pain ▸▸Children do not feel pain to the same degree as adults. ▸▸It is not possible to adequately measure pain in cognitively impaired patients. ▸▸Physical manifestations of pain are more important than self-report measurements. ▸▸Pain does not exist in the absence of detectable tissue damage. ▸▸Pain without an obvious source is usually psychogenic. ▸▸The same stimulus produces the same degree of pain in all individuals. ▸▸Analgesic therapy should not be started until the cause of pain is established. ▸▸Noncancer pain is not as severe as cancer pain. ▸▸Knowledgeable patients have a higher incidence of drug diversion. ▸▸Use of opioids causes all patients to become addicted to them. ▸▸Aggressive pain management is synonymous with prescribing opioids.

2000 to 2010 was designated the Decade of Pain Control and Research by the US Congress3 and, although awareness about pain has increased and attention to assessment has improved, efficacy of treatment may be lagging, and the “opioid epidemic” may further cloud many issues. The healthcare system still lacks clearly articulated primary care practice standards for pain management, taking into consideration that most chronic pain patients present to their primary care providers for treatment. Other than the Joint Commission’s institutional standards, there is a noticeable absence of accountability and competency for adequate assessment and management of pain. The growth of managed care has also led to fragmentation and lack of communication among clinicians, leading to less coordination of care. Financial barriers and lack of access to healthcare ultimately lead to a lower level of care. Clinician perception of the relative importance of pain and its management can also lead to undertreatment. Some healthcare professionals do not want to routinely accept the patient’s self-report of his or her degree of pain as credible. Fear of regulatory scrutiny may also inhibit efforts to control pain. The inability of the patient to report symptoms accurately, which may occur with cognitively impaired patients, may result in poor communication and a decreased likelihood that the clinician will successfully understand the patient’s needs. All of these barriers are associated with several myths about pain and its treatment. (See Table 2.)

The role of referral for consultation in pain management

The complex nature of pain and its management can be quite challenging. Sometimes even deciding to seek expert consultation in clinical management can be confusing due to a lack of education, fear of regulatory scrutiny, or the absence of consensus or guidelines.4 To help clinicians facing these challenges, in 1997 the Federation of State Medical Boards (FSMB) undertook an initiative to develop 54 PWJ | www.painweek.org

model guidelines. They encouraged state medical boards and other healthcare regulatory agencies to adopt policies to encourage adequate and comprehensive pain treatment, including the use of opioids when appropriate for patients with pain. Since the adoption of these model guidelines in April 1998 for the use of controlled substances to manage pain,5 they have been widely distributed to state regulatory agencies and to healthcare providers. The guidelines were endorsed by agencies and organizations including the American Pain Society, the American Academy of Pain Medicine, and the Drug Enforcement Administration. In 2004, the FSMB issued a revised version of the model guidelines, renamed as “policy,” and commented that, despite promulgation of the prior guidelines and other information about the importance of adequately assessing and treating pain, there was increasing concern regarding the abuse, misuse, and diversion of controlled substances.6 Along with this concern was a body of evidence showing that both acute and chronic pain continued to be undertreated. The undertreatment of pain was recognized as “a serious public health problem that results in a decrease in patients’ functional status and quality of life.” Identified circumstances that contribute to this problem included: ○○ Lack of knowledge of: →→ Medical standards about managing pain →→ Current evidence-based research →→ Concrete clinical guidelines for appropriate pain treatment ○○ Clinical expertise at the level of primary healthcare providers ○○ The perception that prescribing adequate amounts of controlled substances may result in unnecessary scrutiny by regulatory authorities ○○ Misunderstanding of addiction and dependence ○○ Lack of understanding of regulatory policies and processes

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The intention of the FSMB policy and the educational initiatives directed towards expert and nonexpert clinicians was clear—to improve the adequacy of pain treatment, while accounting for the issues surrounding appropriate use of modalities and methods in a safe and efficacious manner. Among other often-recommended steps to achieve these goals was the recommendation for the clinician to be “willing to refer the patient as necessary for additional evaluation and treatment in order to achieve treatment objectives. Special attention should be given to those patients with pain who are at risk for medication misuse, abuse, or diversion. The management of pain in patients with a history of substance abuse or with a comorbid psychiatric disorder may require extra care, monitoring, documentation and consultation with or referral to an expert in the management of such patients.” The rationale for referral to an expert can be multifaceted or focused. Sometimes there is a clear reason:

When a comprehensive, multidisciplinary assessment is necessary— ○○ There may be a persistent pain condition for which there is likely no curative treatment, and the available methods of management have been exhausted and unsuccessful. ○○ The referral for an evaluation may be helpful for diagnostic reasons, including interventional diagnostic procedures that go beyond the area of expertise of the primary care clinician. ○○ Referral may be useful for treatment recommendations, including ongoing management options or symptom control. ○○ Assistance may be needed to plan further interventions or management. ○○ An assessment from a specific discipline is considered beneficial (eg, psychosocial evaluation). Members of a multidisciplinary pain management team may include: ○○ Anesthesiologists ○○ Psychiatrists ○○ Psychologists ○○ Physical medicine and rehabilitation specialists ○○ Neurologists ○○ Pharmacists ○○ Nurses ○○ Clergy ○○ Complementary and alternative medicine specialists ○○ Physical or occupational therapists ○○ Social workers Pain clinics may bring all relevant team members “under one roof.” Many pain specialists believe that referrals frequently Q 4 | 2019

are made past the so-called “golden hour,” when their intervention may be of maximal effectiveness, especially in cases of neuropathic and cancer pain.7 Referral to a pain specialist ideally should occur before significant disability or loss of function occurs; pain behaviors or the emergence of maladaptive coping strategies may serve as cues for referral. Some common reasons for referral are below.

An interventional approach is thought to be necessary when… ○○ In certain situations, minimally invasive procedures such as epidural steroid injections, nerve root blocks, facet injections, nerve stimulators, and infusion pumps may be indicated for the purpose of relieving pain directly or for diagnostic purposes. ○○ The intention is to improve functional activity and quality of life. ○○ There are intermediary purposes to defer or delay more invasive procedural approaches such as surgery. ○○ Noninvasive procedures have not yielded the desired goals of treatment.

Medical management is thought to require specific expertise beyond the provider’s scope of clinical practice

The patient may be a management challenge for several reasons including: ○○ Lack of, or poor response to, treatment regimens that have been tried ○○ The patient has been evaluated as an appropriate candidate for opioid therapy, but the opioid risk assessment reveals that the patient is high risk and requires more monitoring than is available ○○ The patient’s assessment reveals a history of prior or current opioid abuse ○○ The patient has specific comorbid conditions needing coordinated care (eg, depression) There can also be a benefit to having a fresh, comprehensive review of a patient with chronic pain. This may be a good reason for expert consultation, especially when the treatment plans that have been attempted are not achieving their desired goals. It is important for the referring clinician to make sure that the patient is adequately informed, before the referral, of the purpose of the referral, and that appropriate expectations are identified. It is critical that the patient does not have the inaccurate perception that the referral represents disbelief or abandonment by the referring healthcare provider. On the contrary, it should be emphasized that the consultant involvement will be time-limited, and that the patient’s ongoing care will then www.painweek.org | PWJ

be provided by his/her primary practitioner again. There should be discussion and agreement with the patient and the primary care provider about the benefits of maintaining the primary care provider as their care coordinator, and as the source for referrals, rather than engaging in self-referrals or cross-referrals from one specialist to another.8 Coordinating referrals with the primary care provider as the “medical home” will likely enhance both communication and the quality of care. References 1. Brennan F, Carr DB, Cousins, M. Pain management: a fundamental human right. Anesth Analg. 2007;105:(1):205–221. 2. Turk D, Melzack R. Handbook of Pain Assessment. 2nd ed. New York: Guilford Press; 2001. 3. Decade of pain control and research. American Pain Society. Available at: www. ampainsoc.org/decadeofpain. 4. Ballantyne JC. The Massachusetts General Hospital Handbook of Pain Management. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; October 1, 2005. 5. Model guidelines for the use of controlled substances for the treatment of pain. Federation of State Medical Boards of the United States, Inc. April 1998. 6. Model policy for the use of controlled substances for the treatment of pain. Federation of State Medical Boards of the United States, Inc. Adopted as policy by the House of Delegates of the Federation of State Medical Boards of the United States, Inc. May 2004. 7. Warfield CA, Bajwa ZH. Principles and Practices of Pain Management. 2nd ed. New York: McGraw-Hill Companies, Inc; 2004. 8. O’Malley AS, Cunningham PJ. Patient experiences with coordination of care: the benefit of continuity and primary care physician as referral source. J Gen Intern Med. 2009 Feb;24(2):170–177.

Our next article in this series will address the epidemiology of pain. Incidence and prevalence of chronic pain in our country will be discussed, along with the burdens of chronic pain on our society.

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I would love to empower my generation to innovate and step up to lead our world into better, safer days.

alexis La PieTRa

Alexis LaPietra DO Medical Director Chief, Pain Management and Addiction Medicine for St. Joseph’s Health

GPS Paterson, NJ Typical Day Up at 6: gym, shower, get the kids to school, at work by 9. Then meetings, lectures, consults, emails, reviewing charts, conducting research, assisting residents/students/nurses, etc. Persona I would love to empower my generation to innovate and step up to lead our world into better, safer days. I hope my voice and my opinions about safe and effective pain management at least motivate others to lead, if not inspire movement into a day when we no longer are wading through the harms associated with prescription opioids. Social Media Habits I am not very social media savvy. I never mastered Twitter or Instagram and although that may limit me in some ways, I find it frees me for more human interactions. I am on Facebook and Linked In enough to keep me somewhat in the loop. Contribution My most meaningful contribution is the recognition of nonopioid medications and interventions as a treatment pathway for acute and chronic pain as opposed to a strict reliance on opioids. This was mostly accomplished through the ALTO (alternatives to opioids) program launched at St. Joseph’s Health in 2016 after I finished my EM residency and Pain Management Fellowship. The concept made it into a House of Representatives bill that was part of a package signed into law by President Trump October 2016. It will provide funding for EDs to develop and implement evidence-based opioid sparing algorithms into day-to-day practice to reduce unnecessary exposure to opioids. ALTO makes practitioners take a second and think about what nonopioid options are possible as a first line treatment. (PS: there are a lot!) People I admire Ellen DeGeneres. She broke down barriers. Although most representative of the diversity in sexual orientation, Ellen has led the conversation on what is means to be different in general—whether through culture, language, or religion. Deep down on an anatomical level we are a bunch of proteins and cells and ultimately ALL THE SAME. Words The Immortal Life of Henrietta Lacks. Dreamland, a chronicle of the Rx opioid/heroin epidemic in the US from the 1950s through today. The Things They Carried, about the men who risked or gave their lives in the Vietnam War. It ignited a desire to advocate for improved mental health and transition programs for soldiers coming home from war. We must love and care for our veterans. They gave a significant amount for our freedom—we must give them WHATEVER they need in return to reintegrate and function post-war. Popcorn Jurassic Park was the most amazing movie I had ever seen when I was 10 years old. It stuck with me because it was so groundbreaking. It’s still one of my favorites. I like Bye Bye Birdie also. It’s pretty old but the singing & dancing is amazing. PAINWeek PAINWeek brings together so many different practitioners. Pain is a complex biopsychosocial experience and it should be treated that way. In order to understand and move pain management forward we need to break down silos and get together every type of practitioner to talk about the challenges and innovations related to treating pain. PAINWeek is a time to meet new folks, learn about innovations, and gain better understanding into this very complex process through different eyes than our own medical specialty. Q 4 | 2019

www.painweek.org | PWJ

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By Doug Gourlay md, msc, frcpc, Dfasam

Risk is not something you can eliminate, but it is something you must be cognizant of. If you don’t look for it, that’s your first deadly sin. And the second one would be not writing it down, and third would be not acting on it.

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A higher prescription amount is associated with persistent opioid use 3 to 6 months after surgery. Insurance claims data of Medicare beneficiaries who underwent surgery between 2009 and 2015 were examined. A total of

cast doubt on daily aspirin use. aha/acc is recommending against the routine use of aspirin in people >70 years or with increased bleeding risk who do not have existing cv disease. A team found that about 1/4 of adults aged >40 without cardiovascular disease— or ~29,000,000 people—reported taking daily aspirin for prevention of heart disease. Of these, some 6.6 million people did so without a physician’s recommendation.1

Birthing women once routinely went home from the hospital with prescriptions for

But

in a study of records from >308,000 women who gave birth from 2008 to 2016, researchers found the % of women filling opioid prescriptions in the days/months after giving birth declined over time. Nearly 1/2 of American women having a baby in the last decade received a prescription for a powerful opioid painkiller as part of their birth experience. And 1 in 2 of every 100 were still filling opioid prescriptions 1 year later. Researchers saw drops of several % points in filling of initial prescriptions over time, although nearly 24% of women who delivered vaginally in 2016, and nearly 73% of those who had a C-section, still had these pills on hand.2

respondents who said they have or would use marijuana or cannabinoids were asked “Why?” 62% said they believe them to be safer than opioids; 57% believe they have fewer side effects than other medications. 37% of millennials, 25% of Gen Xers, and 18% of baby boomers said they have used them for pain. 40% believe CBD sold at truck stops, health food stores, medical marijuana dispensaries, etc, is approved by the FDA. Only 13% said they have/would consider using marijuana or cannabinoids because no other type of pain management works for them.5

who filled an opioid prescription between 30 days before surgery and 14 days after discharge were analyzed. Researchers found that approximately 1 in 7 lung surgery patients (15.7%) and 1 in 8 heart surgery patients (12.5%) became new persistent opioid users for 3 to 6 months after surgery. Patients who were prescribed >60 pills experienced a nearly 2-fold risk of chronic opioid use compared to those who were prescribed ≤27 pills (19.6% vs 10.4%). According to the CDC, the amount of opioid prescriptions in the US peaked in 2012 at ≥255 million and a prescribing rate of 81.3 prescriptions per 100 persons; in 2017, the total number of prescriptions dispensed in the US was >191 million, with a prescribing rate of 58.7 prescriptions per 100 persons. As many as 90% of these patients reported not finishing what was prescribed to them.3

Federal health officials have so far identified

of severe respiratory illnesses reported after use of e-cigarette products in 33 states, with 6 deaths. Although only 8% of US high school students report using cigarettes, an all-time low, 21% report using e-cigarettes in the past month, an all-time high.4

of hydrocodone. CDC reports that prescription opioids continue to contribute to the epidemic with ≥35% of all opioid overdose deaths. On average, 130 Americans die every day from an opioid overdose. A study assessed the effectiveness of 2 pain management methods. A control group (37 patients) was treated with traditional analgesic methods (acetaminophen, hydrocodone-acetaminophen, and IV morphine) on an as-needed escalating basis. Another set (28 patients) was treated with oral acetaminophen and gabapentin, as well as intraoperative intravenous acetaminophen. The majority of patients in both cohorts underwent surgery for resection of oral cavity cancer. Average pain scores within the first 72 hours postoperatively were 2.05 in the multimodal analgesia group and 3.66 in the control group.6

1. https://bit.ly/2PSB13h 2. https://tinyurl.com/y339fq9k 3. https://tinyurl.com/y3owm3s5 4. https://tinyurl.com/y24ly2l2 5. https://tinyurl.com/yxlafbry 6. https://tinyurl.com/yy9zdbna

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medicine as appropriate to the individual patient. If people are going to prescribe controlled substances for any purposes—anxiety, pain, sleep, you name it—they also have to know enough addiction medicine to be able to do a risk assessment. Ask themselves, “Do the risks of an opioid exposure compare favorably to the benefits that are likely to accrue?” Do clinicians know enough about techniques to control the risk that exists? Do they know enough about how to recognize the warning signs that things are going badly and intervene? And importantly, also, do they know how to stop the therapy in a humane way?

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Principles to Guide Pain Care

From Passive to Active: The Better Way to Teach, and Learn Mary Lynn McPherson pharmd, MA, BCPS, CPE

Kevin Zacharoff MD, FACIP, FACPE, FAAP

The four ethical principles that should guide people in treating pain patients are autonomy, nonmaleficence, justice, and beneficence. I happen to consider autonomy to be #1. No matter what happens, the patient gets to have a right to say YES or NO in every single situation, or at least their proxy does. Many people believe nonmaleficence to be the overriding or overarching principle, which is “do no harm” and is probably the one that most people are familiar with when they take the Hippocratic Oath. On the justice side, it is the idea that no matter what you do, it must coincide with what the legal aspects dictate. As guidelines change and as the regulatory scrutiny increases, it’s very important for healthcare providers to understand that they need to consider justice in the risk-benefit analysis to keep themselves out of trouble from a practice perspective. And lastly is beneficence: What’s most likely to benefit the patient? Every patient is different, so the benefit is never going to be exactly the same. Balancing these four ethical principles and trying to mold them in every situation, knowing that in some cases one may be overarching or overriding the others, that’s okay. But no matter what happens, those four principles are rock solid, and they’re not going to change.

Back and Forth… and Back Again

Steve Passik phd

The opioid pendulum probably has been swinging back and forth for thousands of years, and how incredibly polarized opinions have been, from “They are a gift from god” to “They are the devil personified.” I’ve started virtually every talk I’ve given for 30 years showing a pendulum, where one end of the pendulum is opiophobia, the other end is opiophilia, and somewhere in the middle is something approaching some kind of a balance. The two poles are rather extreme, and I think we went to opiophilia, increased opioid prescribing 400% and 500%. A lot of the tools that we need are all around, and now could be one of the safer times to prescribe an opioid if you have the reimbursement time and training to use them. That’s an irony, because now we’ve basically decided that opioids are too risky, and no benefits accrue from the exposure. It’s been sort of insidious, the undermining of the idea that anybody benefits. When I talk about the balance, I talk about applying the principles of addiction

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I think to go to a class for 50 minutes can be like a slow death. We have data that passive learning—me talking at you or assigning you to read a chapter—has a very low yield. So we must immediately follow with an active learning activity. It could be 200 students in a classroom, and I’ll say, “Turn to your neighbor and discuss this for a couple of minutes.” It could be “Please rewrite in your notes this concept that I just explained.” It could be team-based learning where 4 or 5 students get together and wrestle with a case or a multiple choice question and defend why the right answer is correct and the wrong answers are incorrect. Taking that knowledge from the passive learning and putting it to work, that’s how adults learn. I’m also a really big fan of metacognition. Whenever I teach a class, whether online or a face-to-face, I’ll have the students write in their reflective journal. Not “What I did this week.” I don’t want to hear “I read this chapter, and then I did these cases.” I want them to reflect on what were their impressions from that past week or two weeks. For example, “I was really surprised about what we did this week. I thought I would love it, and you know what? I didn’t like it so much.” But more often what I hear is “I really didn’t want to do this activity this week.” I teach an online course on the principles and practice of education, and I make the students use social media as a form of education. I make them log on to Facebook in our closed group, or I make them Tweet. They all go screaming and kicking, particularly into the Twitter world, but, at the end of the course, they finally say, “I can see why this is a valuable educational opportunity.” By having learners do the activity that you’re trying to teach, it dramatically increases their retention and their ability to incorporate that learned activity into their practice.

Wound Care and Painful Itching: Hope and Help from Topicals

Jeanette Jacknin MD

Cannabinoid 1 and cannabinoid 2 receptors are throughout the whole skin, including appendages like hair follicles, nerve fibers, immune cells, basal cells, melanocytes and sebocytes that make sebum. Pain and itch fibers are related in the skin. Because there are sensory nerve fibers that have cannabinoid receptors in the skin and throughout the immune system, they can be influenced by either our own cannabinoid that we make, called anandamide, or topical cream. They’ve done

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studies on patients with itching from end-stage renal disease, which is severe and intractable: 38% had a complete cessation of their itching, which is almost unheard of in that population. In another study, 83% of patients had no more itching from severe chronic itching, prurigo, lichen simplex, which had been intractable, with a topical CBD cream with a high enough concentration to be effective. There’s so much we have to yet discover about which cannabinoids help in which disease. There are over 130 cannabinoids; CBD is just one of them. This is very personalized medicine and people react differently depending on their metabolism and how they absorb things, to different terpenes in the cannabis sativa plant. There are big researchers across the country collecting databases on patients’ experiences on which combination of CBD, cannabigerol, or different amounts of THC or THCA works for them in their disease. We’re talking about helping patients and the science behind it, and double-blind studies, and not about getting high. It’s about pain relief. It’s about improving the quality of the patient’s life. When I’ve taken care of wounds, I’ve had to cut out the dead area. It’s so painful for the patients, and so hard to heal. The topical has shown to help. Anecdotally, for hundreds of years, native people have used topical cannabinoids for wounds and for skin care. As far as wounds go, there was one case study done with three patients who had terrible wounds from pyoderma gangrenosum—terrible pain. A topical cannabinoid actually reduced the pain and helped with the proliferation of new skin cells and helped the wound shrink. All three patients were able to reduce their opioids. There are many, many anecdotal reports, but this was a double-blind study recently in the literature. I’m really hopeful that a lot more research will be allowed to be done.

The Prevalence of Pelvic Girdle Pain During Pregnancy Colleen Fitzgerald MD, MS

Pelvic girdle pain (PGP) in pregnancy is way more common than you would imagine: it’s about 25% of women. But if you include the lumbar spine plus pelvic girdle it’s more like 50% to even 75% of women who have some form of either low back or PGP during pregnancy. The differential diagnosis is not unlike other musculoskeletal presentations. At the top of the list is what we sometimes call sacroiliac joint dysfunction because we don’t know if the true pain generator is the joint itself or the ligamentous structures that surround the joints. But we’re always making sure there’s not lumbar pathologies such as degenerative disc disease, or herniated disc, or a true radiculopathy that could be contributing to a patient’s presentation. We’re always ruling out hip pathologies. So, anything that a pregnant patient brings in to the pregnancy could create pain. Things like labral pathology for example, or prior injuries that could affect the musculoskeletal pelvis. True sciatic neuropathy in pregnancy is actually fairly rare: it only happens about 1% of the time. In a study of ~800 women in Europe during the ‘90s, the majority of patients actually presented with SI joint pain, not sciatic neuropathy. PGP is mainly treated through nonpharmacologic therapies, including physical therapy and aqua therapy. In Europe, acupuncture has been shown to be exceptionally helpful for patients with PGP in pregnancy. But we do a lot as it relates to exercise and physical therapy for treatment. We also use sacroiliac joint belts. Maternity belts have been shown to be helpful. The main point is

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that pregnancy is a huge opportunity to treat this common condition because we know that the majority of women do really, really well with physical therapy, and we knock the pain out. If we actually treat it and knock out the pain, I think we can avoid chronic pain in a great majority of these women. Unfortunately, many of these pain conditions, because we’re so focused on the pregnancy itself, get pushed aside. But we have a huge opportunity to avoid that transition from acute to chronic pain.

Objective Biomarkers for Pain — Promise and Precaution Sean Mackey MD, phd

Would we like to have an objective biomarker of pain? Would we like to have an objective means of determining if somebody is in pain? Can we predict whether somebody will respond to a specific treatment before an injury or surgery, whether that person will go on to get persistent pain or will use opioids persistently? Of course, the answer is yes. We’ve started off with these diagnostic markers of pain, and now the field is moving towards the development of more predictive biomarkers and prognostic biomarkers. Ultimately, the holy grail is to combine brain imaging biomarkers with inflammatory markers, with genetic markers, with others to be able to determine for a particular patient in your clinic what is the right treatment under their particular circumstances. If you had asked me 10 years ago I would have said this goal is not achievable: there’s too much individual variance or variability in all of our experiences. But as time has gone by, I have evolved my opinion to be now emphatically in the camp that we are going to develop excellent objective biomarkers. They’re not going to be perfect, but I think they’re going to help us in guiding treatment decisions, which is the most important thing. But there’s a lot of controversy that remains in the research field over whether this can or can’t be done. And there are legal and ethical concerns that will need to be addressed. If we have an objective way of determining if somebody is in pain or not in pain, can it be misused to deny them treatment, to invalidate their pain? That would be tragic. Is it going to be used by insurance companies to deny treatment for a particular person? We must be very careful about how this is used. It’s both an exciting and a somewhat scary scientific development. There is so much incredible potential, and there is also a significant potential for abusing this technology. I think that the best way forward is bringing a lot of people to the table, all who are stakeholders in different ways, to have discussions about this and find a common path forward where we are developing this exciting technology but making sure that we’re using it in a responsible manner.

www.painweek.org | PWJ

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with

jeremy a.

adler

dmsc, pa-c

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“I can’t remember ever thinking about a profession other than medicine. My parents tell me that I was one who would place bandages on my friend’s cuts and scrapes.” Q

What inspired you to do what you do?

I can’t remember ever thinking about a profession other than medicine. My parents tell me that I was one who would place bandages on my friend’s cuts and scrapes. My father is a physician, my mother a teacher, and jointly they inspired me into a career of service. I was always intrigued by the stories of patients that would be discussed at the dinner table. Being active in the Boy Scouts, and achieving the rank of Eagle, taught me about first aid and leadership. It was my father who introduced me to the PA profession. Medical school was my plan, but following advice from a number of people, I chose the PA path. Just to be certain, and to keep options open, I took MCATs. I needed to know that my scores would have qualified me for medical school. Satisfied with my scores, I embraced the PA profession and charged ahead. I have continued with education and earned both a Masters and Doctorate degree. I believe there is no limit on the knowledge one can attain. I am very appreciative of the support I receive from my amazing wife Danielle, and two boys, Jacob and Jesse. I am also thankful for practicing with outstanding colleagues and staff at Pacific Pain Medicine Consultants.

Why did you focus on pain management?

When I entered practice I had never heard of the specialty of pain management. My vision was practicing in emergency medicine or endocrinology. I quickly discovered that training on the east coast and then entering the market in California meant networking relationships were limited. After lost leads, I heard of a pain physician looking to expand the practice with a PA. I was not enthusiastic to begin with, but I chose to interview, and it was that interview which changed the course of my career. I was told that I likely knew nothing about pain

Q 4 | 2019

management and that what I did know was probably wrong. The physician asked me to shadow him. He highlighted from a career perspective that pain was an amazing balance between medicine, surgery, and psychiatry. Not only did the field involve science, but it also crossed with policy, law, and education, as well as having a profound effect on the patient. That interview was 20 years ago and I haven’t looked back.

Who were your mentors?

William L. Wilson, MD, introduced me to pain management and mentored me into clinical practice. We practiced together for nearly a decade. I was pushed, challenged, and taught to focus on the details, as they all matter. At times we would stay late discussing the most random topics in great detail, trying to better understand our observations, medications, and how to improve patient outcomes. My career transitioned from solely clinical practice to one as a medical educator and leader after I met Marsha Stanton, RN, phd. I have also received mentorship from Gaye Breyman, CAE, the executive director of the California Academy of PAs. Through associations, patient care can be impacted far beyond one individual clinician’s ability to see patients. I feel fortunate to have had opportunities to work on advancing the PA profession, influence policy, and change laws to improve patient care.

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

It is hard to think of not being a healthcare provider, but I think I could have been a park ranger. I think preserving our open spaces and natural resources is really important. Spending time in nature with my family is one of the most relaxing things I do.

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“…expanding the opportunities of what can be accomplished with a PA license has been very exciting.” Q

What is your most marked characteristic?

Being trustworthy is a characteristic I deeply value, and I hope that others would describe me that way. Whether it is communicating to a patient the concerns I might have or expressing my appreciation to my staff for the incredible work they do, I believe being genuine and trustworthy are really important.

What do you consider your greatest achievement?

Watching my two boys grow up and show interest in service, education, and leadership is probably at the top of my list. Professionally, I think that expanding the opportunities of what can be accomplished with a pa license has been very exciting. Different members of the healthcare team come with different education, degrees, licenses, roles, and experiences, but the system only works optimally when the members function well together. I was the first pa in California to have his name on a triplicate prescription printed by the state for controlled substance prescribing; the first pa to obtain surgical privileges within the department of anesthesia at a local hospital (a three-year process); and I’ve earned a doctorate degree. I am coauthor of several clinical practice guidelines; a co-owner in my medical practice; a founding president for a local professional association. I served as president for my state’s pa association, hold leadership roles within the American Academy of Pain Medicine, and gave many educational lectures, including a controlled substance regulatory course that has so far reached two-thirds of the pas in California. Certainly, being awarded Pride of the Profession in 2018 from the California Academy of pas is high on my list of achievements I am proud of.

What is your favorite language?

a Although I took years of Spanish in school, and live 25 miles north of the US/Mexico border, I still struggle to hold a conversation in Spanish. Currently, I am trying to learn Morse code. Although it might not be a “language,” I enjoy the 64 PWJ | www.painweek.org

musicality of the code, and it will expand my enjoyment in my hobby as an amateur radio operator.

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

a I have been wanting to read “Surely You’re Joking, Mr. Feynman!”: Adventures of a Curious Character so I might bring that along. Film: The Blues Brothers. Music: Neil Young’s Decade compilation. Q

What would you like your legacy to be?

I would hope that my legacy would be that the work I have done has made a positive difference. I further hope that I have in some way inspired others to carry on this work.

Plans for the future?

I plan to continue clinical medicine and further expand my efforts in pain policy, education, and research. At the end of the day, there is a finite number of individual patients I can see. To have a greater reach, the system needs to be changed. Advocating for improved pain policies is an effective means to accomplish this goal. Discoveries in pain reduction strategies that are safe, effective, and affordable are desperately needed. I also plan to continue to work in professional education.

What is your motto?

Although it may lack originality, the Scout motto “Be prepared” has served me well. Even when the work is hard, it is important to seek out a “fun” element to keep burnout at bay. Jeremy A. Adler, DMSc, PA-C, is a Senior Pain Management PA, Doctor of Medical Science, Co-Owner, and Chief Operating Officer at Pacific Pain Medicine Consultants in Encinitas, California.

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By Wendy Caster

Across

1. Merchandise 6. Imitating 11. Smidgen 14. Tequila source 15. Type of salami or Christopher Columbus’ birthplace 16. ___-Wan Kenobi 17. PAINFUL, bald, TV deal-maker 19. Garden tool 2 0. Ultimatum words 21. More serious 23. Sculler’s need 24. One Swiss mountain 26. Snooty one 27. Dives 3 0. Hearing-related 33. Maven 36. Meted (with “out”) 38. ___ of the above 39. What a gymbot pumps 4 0. Seeing red 41. Alternative to a king 42. Peel 43. Tubelike structure that bridges the small intestine and the large intestine 44. Part of MIT, in brief 45. Brownish yellow 47. Get ready to be photographed again 49. Wood sorrel mushrooms 51. Fr. holy woman 52. Bro or sis 55. Most klutzy 59. Under cover 61. Can. neighbor 62. PAINFUL judge of talent on TV 6 4. Michael Caine, Paul McCartney, or Lancelot 65. Habituate 6 6. Bolero composer 67. Possessed 6 8. Spat 69. Firewood measure

Down

1. “Yippee!” 2. Greek marketplace 3. Less cooked 4. Really, really not good 5. It has its ups and downs 6. Palindromic Turkish title 7. They’re mightier than swords 8. Prefix for European 9. Christmas songs 10. Form of lead or city in Illinois 11. PAINFUL abolitionist

12. Reedy instrument 13. Seating section 18. Hummable 22. Canadian cop 25. Worse 27. Tanning porch 2 8. Finish second 29. Arrangements 31. Spanish liqueur or South American birds 32. Fast time? 33. Copter’s forerunner or Italian multi-stage bike race 34. Acid eliminated by kidneys 35. PAINFUL director and child star 37. Vernacular 4 6. Hikes in pay 4 8. Milanese misters 5 0. River near Notre Dame 52. Strainer 53. Slacker 54. ____ of the ball

55. Spew 56. Indian continent 57. Erotica, but dirtier 58. Wrongful act 6 0. Get rid of a mosquito 63. New prefix

Puzzle solution: painweek.org/crossword. Q 4 | 2019

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What differentiates radiculopathy from neurogenic intermittent claudication? Education is the best analgesic. September 8â&#x20AC;&#x201D;12â&#x20AC;&#x201A; 2020 The Cosmopolitan of Las Vegas

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