The impact of opioid-induced hyperalgesia for postoperative pain.
Clinical evidence suggests that--besides their well known analgesic activity - opioids can increase rather than decrease sensitivity to noxious stimuli. Based on the observation that opioids can activate pain inhibitory and pain facilitatory systems, this pain hypersensitivity has been attributed to a relative predominance of pronociceptive mechanisms. Acute receptor desensitization via uncoupling of the receptor from G-proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA)-receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days in rodents, and also in humans large-doses of intraoperative micro-receptor agonists were found to increase postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients is often associated with a requirement for increasing doses and the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha2-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor/selectivity.
Koppert
Wolfgang
W
Klinik für Anästhesiologie, Universitätsklinikum Erlangen, Krankenhousstrasse 12, D-91054 Erlongen, Germany. koppert@kfa.imed.uni-erlangen.de
Schmelz
Martin
M
D015760:Alfentanil / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D005283:Fentanyl / Q000627:therapeutic use; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D009020:Morphine / Q000627:therapeutic use; D010149:Postoperative Pain / Q000188:drug therapy*; D011957:Receptors, Opioid / Q000502:physiology
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D015760:Alfentanil; D009020:Morphine; D005283:Fentanyl