title: Mechanisms of opioid-induced tolerance and hyperalgesia.
abstract: Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.
authors.affiliation: Pain and Palliative Care Research Department, Swedish Medical Center, Seattle, Washington 98122-5711, USA. anna.dupen@swedish.org
authors.forename: Anna
authors.initials: A
authors.lastname: DuPen
authors.forename: Danny
authors.initials: D
authors.lastname: Shen
authors.forename: Mary
authors.initials: M
authors.lastname: Ersek
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D019390:Arrestins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015195:Drug Design; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000502:physiology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy; D024802:Nurse's Role; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010597:Pharmacogenetics; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D000071557:beta-Arrestins
chemical_list: D000701:Analgesics, Opioid; D019390:Arrestins; D011949:Receptors, Cholecystokinin; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D000071557:beta-Arrestins; D019204:GTP-Binding Proteins