Many physicians do not fully understand the proper role of opioids in the treatment of injured workers and they do not understand the importance of a biopsychosocial, whole-person approach as promoted in the evidence-based and presumptively correct California DWC Medical Treatment Utilization Schedule (MTUS) Chronic Pain Medical Treatment Guideline 1. The Introduction to this Guideline attempts to establish a conceptual framework for understanding and treating chronic pain including the prescription of opioids and other treatments.

The issue of appropriate current and future use of opioids in the treatment of Chronic Pain is complex, controversial, and timely.

On one side we have the ever increasing problem of increasing deaths and dysfunction from the inappropriate use of prescription opioids, and on the other we have the needs of patients for adequate pain control to facilitate comfort, activity and function. For the practitioner and patient, achieving a balance across the spectrum of outcomes from pain alleviation, untoward side effects, aberrant drug related behavior, drug addiction, drug abuse, drug diversion and potential death, remains problematic.

Scientific studies have shown a dramatic increase in accidental deaths associated with the use of prescription opioids and also an increasing average daily morphine equivalent dose (MED) for the most potent opioids over the past decade. In response to the increasing morbidity and mortality associated with the increasing use of opioids, the Centers for Disease Control and Prevention has released several recommendations for health care providers 2. The recommendations include the notion that use of opioid medications for acute and/or chronic pain should only take place after a determination has been made that alternative therapies have not provided adequate pain relief. Additionally, the lowest effective dose of opioids should be used. Behavioral screening, patient agreements, random, periodic, and targeted urine testing for opioids and other drugs should be strongly considered in patients with noncancer pain, who has been treated with opioids for more than six weeks. If or when a patient’s MED has increased to 120 mg per day or more, without substantial improvement in function and pain, the treating physician should seek advice from a pain specialist.

Use of opioids for chronic noncancer pain (CNCP) remains controversial 3. A 2007 systematic review indicated no clear efficacy of long-term opiate therapy for chronic back pain because no studies have evaluated opiate use beyond 16 weeks 4 and data on the long-term effectiveness of opioids for CNCP are sparse, with inconclusive or mixed results. 5

Although extensive clinical experience suggests that opioids can improve pain and function in some patients6,7, a significant proportion experience no improvement or worsening of symptoms8. Because opioid use is often associated with a variety of potentially serious adverse outcomes, including harms related to drug abuse and diversion. 9, 10

Additionally, there have been increasing reports of problems associated with chronic opioid therapy. Although opiates remain an important tool in reducing pain, it is important that the prescribing physician appreciate the potential adverse effects that may occur with chronic opioid administration, such as immune dysfunction,11 endocrine deficiencies, 12, 13 sleep disorders, 14, 15 and hyperalgesia. 16, 17

Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. This clinical phenomenon causes the patient to experience pain that is significantly more intense than the pain anticipated from actual injury and is caused by 1) decreased tolerance of pain, 2) hypersensitivity of the nerves, and 3) the patient's expectation of the occurrence of pain. Studies have shown opiates produce a long-lasting hyperalgesia that increases in magnitude and duration with continued use. 18, 19, 20, 21

Although it is true that physician acceptance of opioid analgesic usage has relaxed over the years, it remains important to evaluate each patient individually, to ensure effective treatment. In general, there is a belief today that opioids (despite their potential for problems) have a place in the physician’s treatment armamentarium when other methods have failed and when the use of opioids use results in less pain, more function and manageable side-effects.

Assuming non-opioid treatment approaches have failed and that there is adequate pathology to support the use of opioids, the clinician must determine that the use of opioids is beneficial and that the benefits outweigh the risks.

The physician can make this determination using the Four “A’s” of Pain Treatment Outcomes 22 which include: 1) adequate Analgesia (pain relief); 2) improved Activities of Daily Living (physical and psychosocial functioning); 3) manageable or no Adverse effects (untoward side effects); and 4) no evidence of Aberrant drug taking (addiction-related outcomes).

I want to emphasize that symptoms of pain even with reported “benefit” with opioids is not an adequate basis for opioid prescription absent a pathological process consistent with the pain complaints. Opioids are used illicitly for non-pain purposes in our society for both pleasure and habituation (physical dependence and addiction). Considering the controversy and potential danger of opioids, their use must be weighed against the risks associated with use. In other words, the use of opioids for benign musculoskeletal conditions is not medically indicated or reasonable.

Special attention must also be paid to individuals who have a predilection to opioid overuse and abuse. This includes those with a prior history of substance abuse but also people with a history of adverse childhood experiences.

Adverse Childhood Experiences (ACE) including abuse (physical, emotional, sexual, etc.), neglect (physical, emotional, etc.), household dysfunction (violence, mental illness, drug abuse, etc., in the home), and exposure to traumatic stressors increase the likelihood of chronic disability and prescription drug abuse in adulthood. 23, 24

The 2008 ACOEM updated Chronic Pain Chapter Guidelines 25 (I was on the Panel and served as Associate Editor), suggests that opioids should not be used when there is no evidence that they provide increased function in life. Further, it is also recommended that patients on chronic opioid therapy go through a weaning process to see whether the opioids truly make any difference in function and pain management.

In cases where opioids are to be used, they should provide cost effective benefit; less pain and more function with manageable side effects. We should not use a particular opioid when something less costly (i.e., Methadone or a generic drug – assuming efficacy) is available or when there is an alternative available with lesser potential problems such as acetaminophen, NSAIDs, anti-neuropathics, etc., or with functional restoration approaches including education, cognitive behavior therapy, meditation, exercise, and physical rehabilitation. In fact, there is good evidence of cost-effectiveness when a functional restoration approach is provided as an adjunct and concomitantly with medication and interventional approaches.

Once patients have demonstrated improvement in function, concomitant reduction in pain supports attempts to minimize the opioid dose. This should be done slowly and methodically, in conjunction with careful monitoring of the patient’s clinical and functional status. Under such circumstances it is sometimes possible to completely wean the patient from opioids after several months.

If attempts at weaning are accompanied by worsened functional performance, the medication dose can be reinstituted and, perhaps, weaning attempted again after the patient has stabilized. If weaning remains problematic, it is only then that consideration be given to maintenance, long-term opioid use.

Patients considered for long-term opioid use must be made aware of risks and benefits including the aforementioned long term potential adverse effects of opioids: tolerance, addiction, hypogonadism (with secondary osteoporosis) and opioid induced hyperalgesia.

If long-term treatment with an opioid is undertaken for chronic pain, periodic monitoring is essential to optimize benefit and minimize risk during the course of treatment. 26 All patients maintained on chronic opioid therapy should review and sign a formal opioid agreement/contract, to include random urine drug screens. 27

The Official Disability Guidelines 28 (I serve on the ODG Medical Editorial Advisory Board) has established criteria for using of opioids. Briefly, the use of opioids should be part of a treatment plan that is tailored to the patient. Reasonable alternatives to treatment should have been tried. Is the patient likely to improve and has the patient at risk for abuse or addiction? If opioids are not effective, dose escalation may not prove beneficial. Is there pathology to justify use of opioids? Is there psychiatric comorbidity in one of the diagnostic categories that have not been shown to have good success with opioid therapy: conversion disorder; somatization disorder; pain disorder associated with psychological factors (such as anxiety or depression, or a previous history of substance abuse)? Only one practitioner should be prescribing opioids. The lowest possible dose should be prescribed to improve pain and function. The physician should document ongoing review and documentation of pain relief, functional status, appropriate medication use, and side effects. Satisfactory response to treatment may be indicated by the patient's decreased pain, increased level of function or improved quality of life.

There are other Guidelines that provide similar recommendations which include:

• Institute For Clinical System Improvement (ICSC) Health Care Guideline: Assessment and Management of Chronic Pain, 29 Fourth Edition, November 2009)
• Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain 30
• Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain 31
• Washington State Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain 32
• The American Pain Society: Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain 33

The reader is also encouraged to view and download a copy of the American Chronic Pain Association Consumer Guide to Pain Medications & Treatment (I am the Senior Author). 34

In summary, while opioids can prove extremely effective in managing chronic pain in certain individuals, their use is fraught with serious problems. Opioids should be prescribed with extreme caution and their sustained use must be justified by increased function, decreased pain and manageable side-effects.

While not the focus of this article, but highly relevant, is that a Functional Restoration approach 35 to chronic pain treatment is recommended and strongly supported in the Introduction to the current Chronic Pain Treatment Guideline in the California DWC’s Medical Treatment Utilization Schedule (MTUS). 36

References

1 DWC Medical Treatment Utilization Schedule (MTUS) Chronic Pain Medical Treatment Guidelines.
Available at: http://www.dir.ca.gov/dwc/DWCPropRegs/MTUS_Regulations/MTUS_ChronicPainMedicalTreatment
Guidelines.pdf or http://tinyurl.com/MTUSCPMTG.

2 Centers for Disease Control and Prevention, National Center for Injury Prevention and Control.
CDC’s Issue Brief: Unintentional Drug Poisoning in the United States. Available at:
http://www.cdc.gov/HomeandRecreationalSafety/Poisoning/brief.htm.2010.

3 Chou, R., Fanciullo, g, Fine, p, Miaskowski, C, Passik, S., and Portenoy, R. “Opioids for Chronic Noncancer Pain: Prediction and Identification of Aberrant Drug-Related Behaviors: A Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline” in The Journal of Pain, Vol 10, No 2 (February), 2009: pp 131-146.

4 BA Martell, PG O'Connor, RD Kerns, WC Becker, KH Morales, TR Kosten and DA Fiellin. "Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction." Annals of Internal Medicine 146(2) (2007) 116-127.

5 Noble M, Tregear SJ, Treadwell JR, Schoelles K: Longterm opioid therapy for chronic oncancer pain: A systematic review and meta-analysis of efficacy and safety. J Pain Sympt Manage 35:214-228, 2008.

6 Furlan AD,Sandoval JA, Mailis-Gagnon A, Tunks E: Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. CMAJ 174:1589-1594, 2006.

7 Kalso E, Edwards JE, Moore RA, McQuay HJ: Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain 112:372-380, 2004.

8 Allan L, Richarz U, Simpson K, Slappendel R: Transdermal fentanyl versus sustained release oral morphine in strong- opioid naive patients with chronic low back pain. Spine 30: 2484-2490, 2005.

9 Hojsted J, Sjogren P: Addiction to opioids in chronic pain patients: A literature review. Eur J Pain 11:490-518, 2007.

10 Moore RA, McQuay HJ: Prevalence of opioid adverse events in chronic non- malignant pain: Systematic review of randomised trials of oral opioids. Arthritis Res Ther 7:R1046-R1051, 2005.

11 Sacerdote P. Effects of opioids on the immune system: experimental evidence for immunomodulatory effects of opioids. In: Machelska H, Stein C, eds. Immune Mechanisms of Pain and Analgesia. Advances in Experimental Medicine and Biology. Vol 521. Georgetown, Tex: Landes Bioscience; 2002.

12 Williams KL, Ko MC; Rice KC; and Woods JH. "Effect of opioid receptor antagonists on hypothalamic-pituitary-adrenal activity in rhesus monkeys." Psychoneuroendocrinology. 28(4) (2003) 513-528.

13 Guido M, Romualdi D; and Lanzone A. "Role of opioid antagonists in the treatment of women with glucoregulation abnormalities." Curr Pharm Des. 12(8) (2006) 1001-1012.

14 J. Staedt, F. Wassmuth, G. Stoppe, G. Hajak, A. Rodenbeck, W. Poser and E. Ruther. "Effects of chronic treatment with methadone and naltrexone on sleep in addicts." European Archives of Psychiatry and Clinical Neuroscience 246(6) October 1996 305-309.

15 Dimsdale J, Norman D, Dejardin D, Wallace M. The effects of opioids on sleep architecture. J Clin Sleep Med. 2007 Feb 15; 3 (1):33-36.

16 Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G (2001) Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci 21:4074-4080.

17 Sokolowska M, Siegel S, Kim JA Intraadministration associations: conditional hyperalgesia elicited by morphine onset cues. J Exp Psychol Anim Behav Process (United States), Jul 2002, 28(3) p309-320.

18 King T, Gardell LR, Wang R, et al. Role of NK-1 neurotransmission in opioid- induced hyperalgesia. Pain (Netherlands), Aug 2005, 116(3) p276-288.

19 Celerier E, Laulin JP, Corcuff JB, Le Moal M, Simonnet G (2001) Progressive enhancement of delayed hyperalgesia induced by repeated heroin administration: a sensitization process. J Neurosci 21:4074-4080.

20 Gu G, Kondo I, Hua XY, et al. Resting and evoked spinal substance P release during chronic intrathecal morphine infusion: parallels with tolerance and dependence. J Pharmacol Exp Ther (United States), Sep 2005, 314(3) p1362- 1369.

21 Koppert, W. "Opioid-induced analgesia and hyperalgesia." Schmerz. 19(5) (2005) 392-394.

22 Passik, S. “Issues in Long-term Opioid Therapy: Unmet Needs, Risks, and Solutions.” Mayo Clin Proc. 2009;84(7):593-601.

23 Centers for Disease Control and Prevention (CDC) Adverse Childhood Experiences (ACE) Study http://www.cdc.gov/ace/findings.htm

24 Impact of Early Life Trauma on Health and Disease: The Hidden Epidemic; R Lanius, E Vermetten, C Pain, eds.; Cambridge University, Press, 2010; Chapter 8.

25 American College of Occupational and Environmental Medicine. Occupational medicine practice guidelines, chronic pain chapter update. Beverly Farms, MA: OEM Press. 2008.

26 Portenoy RK: Opioid therapy for chronic nonmalignant pain: A review of the critical issues. J Pain Symptom manage 11:203-217, 1996.

27 American College of Occupational and Environmental Medicine. Occupational medicine practice guidelines, chronic pain chapter update. Beverly Farms, MA: OEM Press. 2008.

28 Official Disability Guidelines at http://www.odg-twc.com

29 Institute For Clinical System Improvement (ICSC) Health Care Guideline: Assessment and Management of Chronic Pain, Fourth Edition, November 2009) - http://tinyurl.com/ICSI-Chronic-Pain.

30 Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain. Available at: http://www.useonlyasdirected.org/uploads/UDOH Opioid Guidelines Summary(2).pdf. 2009.

31 Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non- Cancer Pain.
Available at: http://nationalpaincentre.mcmaster.ca/opioid. 2010.

32 Washington State Interagency Guideline on Opioid Dosing for Chronic Non- cancer Pain.
Available at: http://www.agencymeddirectors.wa.gov/opioiddosing.asp. 2010 Update.

33 Opioid Treatment Guidelines: Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain. The Journal of Pain, Vol 10, No 2 (February), 2009: pp 113-130.
Available at: http://www.useonlyasdirected.org/uploads/APS- AAPM Chronic Opioid Therapy Guidelines.pdf or http://tinyurl.com/APS-CP-Guideline

34 American Chronic Pain Association Consumer Guide to Pain Medications & Treatment.
Available at: http://www.theacpa.org/uploads/ACPA_Consumer_Guide_2011 final.pdf or
http://tinyurl.com/ACPA-Consumer-Guide-2011

35 Functional Restoration and Chronic Pain Management. Steven D. Feinberg, MD, Rachel M. Feinberg, PT, DPT, & Robert J. Gatchel, PhD, ABPP in Critical Reviews in Physical and Rehabilitation Medicine 20(3): 221-235 (2008).

36 DWC Medical Treatment Utilization Schedule (MTUS) Chronic Pain Medical Treatment Guidelines.
Available at: http://www.dir.ca.gov/dwc/DWCPropRegs/MTUS_Regulations/MTUS_ChronicPainMedicalTreatment
Guidelines.pdf or http://tinyurl.com/MTUSCPMTG.