Substance P potentiates thermal hyperalgesia induced by intrathecal administration of D-serine in rats

AIM: To investigate the functional interaction between substance P ( SP) an d D-serine, agonist for glycine regulatory site of N-methyl-D-aspartate ( N MDA) receptor, in processing spinal nociception. METHODS: Behavior studies, by testing tail-flick latency (TFL) combined with intrathecal application of drugs, were conducted in lightly anesthetized rats. RESULTS: Decrease in TFL was observed 1.5 min after intrathecal injection of D-serine 1000 mnol . Following pretreatment with SP 0.05 nmol 6 min prior to injection of D-se rine 10 nmol, D-serine-induced decrease in TFL was greatly enhanced. The po tentiation was blocked by co-administration of 7-chlorokynurenic acid I pmo l, the selective antagonist for glycine regulatory site of NMDA receptor, o r H-7 10 mu mol, the PKC non-selective inhibitor, with SP 0.05 mnol. CONCLU SION: SP potentiates the D-serine-induced thermal hyperalgesia. Glycine reg ulatory site of NMDA receptor and intracellular protein kinase system may p articipate in the interaction of SP and NMDA receptor in the spinal cord.