[Opioid-induced hyperalgesia. Pathophysiology and clinical relevance].
Opioids are the drugs of choice for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G-proteins, up-regulation 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, which might by reflected by clinical observations that large doses of intraoperative micro-receptor agonists increased postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha(2)-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor selectivity.
Koppert
W
W
Klinik für Anästhesiologie, Universitätsklinikum Erlangen. koppert@kfa.imed.uni-erlangen.de
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists
D018690:Excitatory Amino Acid Agonists; D009292:Narcotic Antagonists; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D000262:Adenylyl Cyclases