Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Abstract

While opioids remain a valid and effective analgesic strategy for patients suffering from a wide variety of painful conditions, they are not a panacea. Increasingly, physicians must balance patient expectations of adequate pain control with known limitations of opioid pharmaceuticals including adverse effects, tolerance, addiction, withdrawal, and drug diversion. Further complicating the issue over the last decade is a growing body of evidence suggesting chronic opioid use may unexpectedly worsen the perception of pain in some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH), fundamentally changes our understanding of opioid pharmacodynamics and may influence our approach to management of chronic pain. This manuscript describes the concept OIH and provides an overview of basic science and clinical research to date attempting to characterize this syndrome, as well as ascertain its clinical relevance. The potential existence of OIH in humans is framed within the context of our current understanding of opioids and our prescribing patterns so that physicians may begin to incorporate these ideas into their philosophy of pain management as further information develops. Animal studies reliably validate OIH in controlled models. Rigorous research protocols in humans are lacking, and we cannot yet confidently conclude that OIH manifests in clinically significant ways. However, clinicians should consider the possibility of OIH when evaluating outcomes of patients on chronic opioid therapy.Keywords Opioids . Hyperalgesia . Opioid-induced hyperalgesia . Chronic pain Current Opioid ParadigmPhysicians regularly prescribe opioids for control of moderate to severe pain in the acute care setting. This includes administration in emergency, outpatient, and inpatient environments for patients suffering from a variety of acute and chronic painful conditions. Our current paradigm for opioid utilization suggests they provide effective analgesia for short-term use in most patients. Unfortunately, the risk of adverse effects or addiction is not rare and may be difficult to accurately quantify [1]. Regular prescription of opioids also occurs in the long-term care setting for patients with cancer-related pain offering effective pain relief and limited concern for addiction. However, long-term use of opioids for treatment of certain chronic conditions such as back pain, fibromyalgia, or neuropathic pain syndromes sparks more debate regarding therapeutic efficacy, adverse effects, and potential for misuse, abuse, and diversion of prescription opioids. Concerns regarding opioid use for patients with chronic non-cancer pain may relate to a subset of these patients who require significant dose escalation over time, visit multiple providers seeking opioid prescriptions, and report insufficient pain relief despite high dose therapy. These scenarios generate several concerns including the possibility that chronic opioid administration may be an ineffective strategy for long-term analgesia. Emerging evidence suggests t...

Rising Opioid Prescribing in Adult U.S. Emergency Department Visits: 2001–2010

“…Although the true clinical effect of opioidinduced hyperalgesia has yet to be defined, increased pain perception on the part of patients may drive opioid prescribing patterns in patients already on chronic opioid therapy. 19,20 Opioid prescriptions in ED visits by black patients increased by 84%, but despite this larger relative increase, black patients are still less likely to be prescribed opioids than white patients. Interestingly, the magnitude of the disparity in opioid prescribing between whites and blacks decreased significantly over the 10-year period.…”

Correlates of prescription opioid therapy in Veterans with chronic pain and history of substance use disorder

“…In one scenario, elevated pain ratings in this group of participants prescribed LOT may represent reductions in pain severity from even higher pain ratings observed prior to opioid therapy initiation, albeit to levels still greater than pain ratings endorsed by those not prescribed opioids. Alternatively, participants prescribed LOT may have experienced near alleviation of pain when first initiating opioid therapy but over time developed opioid tolerance or opioid-induced hyperalgesia related to the chronicity of opioid therapy, resulting in a rebound of pain [48][49]. Longitudinal studies are needed to describe pain trajectories for patients with SUD prescribed opioid therapy for chronic pain to inform clinicians about when to initiate, maintain, and discontinue opioid therapy for those with SUD histories.…”

The Chronic Pain Patient in the Emergency Department

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