The role of glutamate in opiate descending inhibition of nociceptive spinal reflexes.
The present experiment examined descending inhibition of the nociceptive tail-flick reflex produced by microinjection of morphine and glutamate into the periaqueductal gray (PAG) matter and the neurotransmitters mediating the inhibition at the level of the nucleus raphe magnus (NRM). The longlasting opiate analgesia was significantly reduced by microinjection of excitatory amino acid antagonists 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylate (PCB, 3.25 mumol) or DL-2-amino-5-phosphono-valerate (APV, 25.38 mumol) into the NRM, whereas the short-lived glutamate analgesia was not. This indicates that although both opiate and non-opiate analgesia may originate in the PAG, the former is relayed through the NRM, whereas the latter is relayed by additional or different nuclei in the medulla. Two observations shed light on the question which receptors mediate the above effect in the NRM. First, PCB blocked morphine analgesia at doses that were 8 times lower than doses of APV that were effective. Second, analgesia produced by injection of glutamate into the NRM was antagonized by PCB (3.25 mumol), whereas APV (25.38 mumol) failed to do so. Together these results indicate that kainate/quisqualate, but not N-methyl-D-aspartate (NMDA), receptors are implicated in the NRM as a relay station in opiate descending inhibition.
van Praag
H
H
Department of Psychology, Tel Aviv University, Ramat Aviv, Israel.
Frenk
H
H
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D010879:Piperazines; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; C045882:1-(4-chlorobenzoyl)piperazine-2,3-dicarboxylic acid