Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Neurosci Res. 2010 May;67(1):18-24. doi: 10.1016/j.neures.2010.01.006. Epub 2010 Jan 22.
It is well known that intrathecal administration of substance P (SP) induces thermal hyperalgesia, but the mechanisms underlying the maintenance of SP-induced thermal hyperalgesia remain to be clarified. Thus, to clarify the receptors involved in the maintenance of SP-induced thermal hyperalgesia, the effect of administering SP or glutamate receptor agonists, NMDA or AMPA, under SP-induced thermal hyperalgesia was investigated. Also, the effect of pretreatment with protein kinase inhibitors on scratching behavior by NMDA or AMPA under SP-induced thermal hyperalgesia was examined. Under SP-induced thermal hyperalgesia, the number of scratchings following SP administration was time-dependently suppressed, whereas the number of scratchings after NMDA or AMPA administration was markedly enhanced and SP-induced thermal hyperalgesia was attenuated by pretreatment with NMDA or AMPA receptor antagonist. Furthermore, pretreatment with kinase inhibitors significantly attenuated the enhancement of scratching behavior by NMDA or AMPA under SP-induced thermal hyperalgesia. These findings indicate that SP-induced thermal hyperalgesia may be maintained through the enhanced responsiveness of NMDA or AMPA receptors, but not the receptor of SP, mediated by kinases.
众所周知，鞘内给予 P 物质（SP）会引起热痛觉过敏，但维持 SP 诱导的热痛觉过敏的机制仍有待阐明。因此，为了阐明参与维持 SP 诱导的热痛觉过敏的受体，研究了在 SP 诱导的热痛觉过敏下给予 SP 或谷氨酸受体激动剂 NMDA 或 AMPA 的效果。此外，还研究了蛋白激酶抑制剂预处理对 NMDA 或 AMPA 引起的 SP 诱导的热痛觉过敏下搔抓行为的影响。在 SP 诱导的热痛觉过敏下，SP 给药后搔抓的次数随时间呈依赖性抑制，而 NMDA 或 AMPA 给药后搔抓的次数明显增加，NMDA 或 AMPA 受体拮抗剂预处理可减轻 SP 诱导的热痛觉过敏。此外，激酶抑制剂预处理可显著减弱 SP 诱导的热痛觉过敏下 NMDA 或 AMPA 引起的搔抓行为增强。这些发现表明，SP 诱导的热痛觉过敏可能通过激酶介导的 NMDA 或 AMPA 受体的反应性增强而维持，而不是 SP 受体。
