Electrophysiological studies on the spinal roles of endogenous opioids in carrageenan inflammation.
This electrophysiological study uses the mixed peptidase inhibitor kelatorphan and the selective kappa-antagonist nor-binaltorphimine (nor-BNI) to investigate whether there is altered modulation of spinal nociceptive transmission by endogenous opioids 3 h after injection of carrageenan into the ipsilateral paw. Intrathecal kelatorphan (5-250 micrograms) inhibited the C-fibre evoked response of dorsal horn neurones in both normal and carrageenan animals, with no difference in this inhibitory effect found between the 2 groups of animals. In both groups of animals, this inhibition reached a plateau at 50%. Thus there was no change in the effects exerted by the spinal enkephalins at this point in the inflammatory state. Nor-BNI (10 and 100 micrograms) produced a bidirectional change in the C-fibre evoked response of dorsal horn neurones in both normal and carrageenan animals, facilitating the evoked response of some neurones whilst inhibiting others. The magnitude of the change in the neuronal response induced by nor-BNI in carrageenan animals was significantly greater than that seen in normal animals, suggesting a greater release of spinal dynorphin in the inflammatory state. Dorsal horn neurones showed a bidirectional change in response as carrageenan-induced inflammation developed, although the direction of this change did not correlate with the subsequent direction of effect of nor-BNI. There was, however, a significant correlation between the magnitude of the change in the C-fibre evoked response after the injection of carrageenan and the magnitude of change produced in the same cells by nor-BNI.(ABSTRACT TRUNCATED AT 250 WORDS)
Stanfa
Louise C
LC
Department of Pharmacology, University College London, London WC1E 6BT UK.
Dickenson
Anthony H
AH
D000700:Analgesics; D000818:Animals; D002351:Carrageenan; D004151:Dipeptides; D004399:Dynorphins / Q000378:metabolism; D004594:Electrophysiology; D004723:Endorphins / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D008839:Microelectrodes; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D000700:Analgesics; D004151:Dipeptides; D004723:Endorphins; C051844:norbinaltorphimine; C042591:kelatorphan; D009271:Naltrexone; D004399:Dynorphins; D002351:Carrageenan