Substance P potentiates thermal hyperalgesia induced by intrathecal administration of D-serine in rats.
OBJECTIVE
To investigate the functional interaction between substance P (SP) and D-serine, agonist for glycine regulatory site of N-methyl-D-aspartate (NMDA) 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 nmol. Following pretreatment with SP 0.05 nmol 6 min prior to injection of D-serine 10 nmol, D-serine-induced decrease in TFL was greatly enhanced. The potentiation was blocked by co-administration of 7-chlorokynurenic acid 1 pmol, the selective antagonist for glycine regulatory site of NMDA receptor, or H-7 10 micromol, the PKC non-selective inhibitor, with SP 0.05 nmol.


CONCLUSIONS
SP potentiates the D-serine-induced thermal hyperalgesia. Glycine regulatory site of NMDA receptor and intracellular protein kinase system may participate in the interaction of SP and NMDA receptor in the spinal cord.
Zhang
Y H
YH
Shanghai Institute of Physiology, Chinese Academy of Sciences, Shanghai 200031, China.
Shu
Y S
YS
Zhao
Z Q
ZQ
D000818:Animals; D004357:Drug Synergism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000819:agonists; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D012694:Serine; D016202:N-Methylaspartate