Opioid Induced Hyperalgesia: Clinical Implications for the Pain Practitioner

Abstract

Opioids have been and continue to be used for the treatment of chronic pain. Evidence supports the notion that opioids can be safely administered in patients with chronic pain without the development of addiction or chemical dependency. However, over the past several years, concerns have arisen with respect to administration of opioids for the treatment of chronic pain, particularly non-cancer pain. Many of these involve legal issues with respect to diversion and prescription opioid abuse. Amongst these, opioid induced hyperalgesia (OIH) is becoming more prevalent as the population receiving opioids for chronic pain increases. OIH is a recognized complication of opioid therapy. It is a pro-nocioceptive process which is related to, but different from, tolerance. This focused review will elaborate on the neurobiological mechanisms of OIH as well as summarize the pre-clinical and clinical studies supporting the existence of OIH. In particular, the role of the excitatory neurotransmitter, Nmethyl-D-aspartate appears to play a central, but not the only, role in OIH. Other mechanisms of OIH include the role of spinal dynorphins and descending facilitation from the rostral ventromedial medulla. The links between pain, tolerance, and OIH will be discussed with respect to their common neurobiology. Practical considerations for diagnosis and treatment for OIH will be discussed. It is crucial for the pain specialist to differentiate amongst clinically worsening pain, tolerance, and OIH since the treatment of these conditions differ. Tolerance is a necessary condition for OIH but the converse is not necessarily true. Office-based detoxification, reduction of opioid dose, opioid rotation, and the use of specific NMDA receptor antagonists are all viable treatment options for OIH. The role of sublingual buprenorphine appears to be an attractive, simple option for the treatment of OIH and is particularly advantageous for a busy interventional pain practice. Key words: Opioid hyperalgesia, hyperalgesia, tolerance, NMDA receptor antagonists, NMDA receptor induced hyperalgesia, spinal dynorphin induced hyperalgesia, descending facilitation and hyperalgesia, buprenorphine and hyperalgesia, opioid detoxification, officebased detoxification, complications of opioid therapy