NK1受体介导a,β-meATP外周注射导致急性疼痛的机制研究

The mechanism study of NK1 receptor mediating acute pain induced by peripheral injection of a,β-meATP

目的在探讨P物质受体NK1在a,β-meATP外周注射引起外周伤害刺激引起疼痛的作用及作用机制。方法笔者采用P2X3受体特异性激动剂a,β-meATP给与大鼠足底注射建立伤害性急性疼痛模型。笔者给与大鼠射NK1受体选择性抑制剂S3144观察其对a,β-meATP足底注射引起伤害反应的影响。同时笔者采用免疫组化的方法观察大鼠背根神经节(DRG)上的NK1受体的表达的率以及S3144椎管内注射对其表达的影响。结果大鼠足底注射a,β-meATP 5分钟时出现显著的缩脚反应,而缩脚反应出现高峰的时间为注射后20分钟。而对照组足底注射生理盐水则缩脚次数不明显。两组缩脚次数有显著差异性P<0.05。椎管注射抑制剂TNP-ATP和S3144之后缩脚次数明显减少P<0.05。NKI受体在a,β-meATP足底注射在DRG神经元中小细胞上与足底注射生理盐水相比显著增加P<0.05,而椎管内注射S3144显著抑制NK1受体的表达。结论 NK1受体在DRG通过P2X3受体导致外周伤害性刺激引起的疼痛伤害性反应。

Objective To investigate the mechanism of substance P （SP） receptor NK1 mediating acute pain induced by peripheral injection of a,β-meATP. Method The pain model was established by subcutaneous injection a,β-meATP into hindpaws. To observe the harmful response, the intrathecal injection of S3144, a selective inhibitor of SP, was performed. TNP-ATP, a selective inhibitor of P2X3 receptor, was performed re-spectively. Meanwhile, we observed the expression of NK1 receptor in dorsal root ganglion （DRG） by immunohistochemistry. Result The response of withdrawal hindpaws occured 5 minutes following a,β-meATP injection and the significant response occured 20 minutes following injection of a,β-meATP. There was no significant response occurred in control group rats challenged saline. The significant response of withdrawal hindpaws was markedly inhibited by individual intrathecal injection of TNP-ATP and S3144. The results of immunohistochemistry indicated that NK1 mainly ex-pressed in the small and medium-sized neuron cells of DRG. The expression of NK1 was significantly high in a,β-meATP injection group than in control group. The high expression induced by a,β-meATP injection was significantly inhibited by intrathecal injection of S3144. Conclusion The acute pain induced by peripheral injection of a,β-meATP was mediated by NK1.