Neurophysiology of opioid poorly responsive pain.
This review has covered the five potential causes for opioid poorly responsive pain, namely (a) a loss of opioid receptors on the spinal terminals of C-fibres as a result of peripheral nerve damage, (b) an accumulation of morphine-3-glucuronide, (c) changes in the non-opioid peptides, F8Fa or CCK, either spinally or supraspinally, (d) actions of the opioid peptide dynorphin and (e) spinally generated hypersensitive states via activation of the NMDA receptor. The loss of opioid receptors is likely to be important where peripheral nerve pathology or compression occurs, but the evidence suggests that increasing the dose will overcome the reduced opioid response. Morphine-3-glucuronide is unlikely to be a factor, nor is dynorphin, but the endogenous peptides CCK and F8Fa may be important. Finally, there is an association between the NMDA receptor and hyperalgesia/allodynia and reduced opioid sensitivity. Dextrorphan and ketamine reduce NMDA mediated events and so are available to test this hypothesis.
Dickenson
A H
AH
Department of Pharmacology, University College London.
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism; D006801:Humans; D009020:Morphine / Q000008:administration & dosage / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000628:therapy*; D009482:Neurophysiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D013565:Sympatholytics / Q000494:pharmacology
D000701:Analgesics, Opioid; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D013565:Sympatholytics; D003917:Dextrorphan; D016202:N-Methylaspartate; D003915:Dextromethorphan; D004399:Dynorphins; D009020:Morphine; D003000:Clonidine