P物质增强大鼠鞘内注射D—丝氨酸诱发的热痛过敏

目的：研究脊髓伤害性信息传递中P物质（SP）与N－甲基－D－天冬氨酸（NMDA）受体甘氨酸位点激动剂D－丝氨酸（D-serine)之间的功能联系。方法：在浅麻大鼠，采用行为学方法，测定甩尾反射潜伏期（TFL）并结合鞘内给药途径观察药物作用。结果：鞘内注射D-serine 1000nmol后1．5分钟，TEL明显缩短；在注射D-serine 10nmol前6分钟鞘内施加SP 0.05nmol,明显增强D-serine 10nmol引起的TEL缩短效应；选择性NMDA受体甘氨酸位点拮抗剂7－氯犬尿酸1pmol及非选择性PKC抑制剂H－7 10μmol均可阻断这种增强作用。结论：SP可使D－丝氨酸诱发的热痛过敏明显加强，NMDA受体甘氨酸位点及胞内蛋白激酶系统参与了脊髓SP与NMDA受体的相互作用。

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

AIM: 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. CONCLUSION: 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.