Known unknowns: A review of opioid-induced hyperalgesia

Abstract

AbstractOpioid-induced hyperalgesia (OIH) is a relatively new paradigm that has added to the already growing uncertainty surrounding long-term opioid treatment. OIH is the oversensitization to stimuli in the nervous system resulting from opioid exposure and subsequent neuroplastic changes. Because of its novelty and difficulty in identification, the true prevalence of OIH is unknown. Several mechanisms have been proposed for its development. These include changes in the N-methyl-D-aspartate system, descending pathway modulation, dynorphin activity, inflammatory changes mediated by cyclooxygenase, and increased sensitivity to excitatory neurochemicals. The clinical controversy regarding the management of OIH is due largely to the lack of guidance in diagnosis and lack of quality evidence to direct treatment. As a diagnosis of exclusion, several alternative causes of antianalgesia must be ruled out before OIH can be declared. Pharmacodynamic phenomena such as opioid tolerance share overlapping mechanisms with OIH and may present similarly. Pharmacokinetic changes such as drug-induced or disease-induced alterations to the cytochrome P450 or P-glycoprotein systems should also be excluded as causes of increased opioid demand that may be seen as OIH. Certain pharmacologic agents, such as N-methyl-D-aspartate receptor antagonists, alpha2 receptor agonists, and cyclooxygenase inhibitors, have been identified as possible treatments to reverse the effects of OIH. Opioid rotation and dose reductions have also been used with some degree of success. Pharmacist involvement in the identification and management of OIH will be central to success because of the unique expertise they offer. The quality of these studies is limited by study design, small sample sizes, and lack of generalizability to chronic pain patients with long-standing opioid use.