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.
Brain Function Research Unit, Department of Physiology, University of the Witwatersrand Medical School, Johannesburg 2193 South Africa.
Graham D
GD
Sher
Steven M
SM
Cartmell
Linda
L
Gelgor
Duncan
D
Mitchell
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