Role of N-methyl-D-aspartate and opiate receptors in nociception during and after ischaemia in rats.
We have investigated the effects of systemic administration of two N-methyl-D-aspartate (NMDA) receptor antagonists and two opiate agonists on nociception during and after tail ischaemia in conscious rats. The two NMDA receptor antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride, did not alter tail flick latencies in rats not subjected to ischaemia but inhibited post-ischaemic hyperalgesia (PIH) in a dose-dependent manner. Neither of these agents impaired motor function of the rats, as assessed by rotarod performance, suggesting a purely sensory antinociceptive effect. The antinociceptive effect of APV during reperfusion following ischaemia was not antagonised by the mu-opiate receptor antagonist naloxone (1 mg/kg). The two opiate receptor agonists, morphine and pethidine, increased tail flick latencies in rats not subjected to ischaemia, inhibited PIH in a dose-dependent manner, and also caused significant motor malfunction, all in naloxone-reversible fashion. We conclude that the role of the NMDA receptor in mediating afferent nociceptive traffic is confined to its involvement in neuronal events mediating hyperalgesia.
Sher
Graham D
GD
Brain Function Research Unit, Department of Physiology, University of the Witwatersrand Medical School, Johannesburg 2193 South Africa.
Cartmell
Steven M
SM
Gelgor
Linda
L
Mitchell
Duncan
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D015424:Reperfusion; D013623:Tail / Q000098:blood supply
D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D009270:Naloxone; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; D008614:Meperidine