BoNT-A对慢性坐骨神经结扎大鼠疼痛行为学及脊髓中Fos蛋白的影响

Effects of botulinum toxin type A on behavior and Fos protein expression in CCI rat models

目的探讨肉毒毒素A(BoNT-A)对神经病理性疼痛大鼠疼痛行为学及脊髓背角Fos蛋白表达的影响。方法建立雄性SD大鼠慢性坐骨神经结扎(CCI)疼痛模型,CCI术后第3天开始,同侧肢体足底皮下注射BoNT-A30U/kg和等容积生理盐水,给药前、给药后1、3、5、7、14d,采用von-Frey纤维细丝机械刺激法和热辐射刺激法评定大鼠机械刺激缩足反射阈值(MWT)和热刺激缩足反射潜伏期(TWL),观察大鼠疼痛行为学变化,根据变化结果,给药后第5天取相应脊髓节段标本,运用免疫组织化学法观察脊髓背角Fos蛋白表达。结果 CCI神经病理性疼痛模型大鼠建立后,CCI组同侧MWT和TWL均明显降低,且脊髓水平Fos蛋白表达明显增多;同侧足底注射BoNT-A30U/kg后,其MWT和TWL均显著增加,脊髓水平Fos蛋白表达明显减少。结论足底注射BoNT-A抑制脊髓水平Fos蛋白的表达,能减轻神经病理性疼痛模型大鼠的机械性触诱发痛和热痛觉过敏。

Objective To evaluate the analgesic effect of botulinum toxin type A（BoNT-A） against the chronic constriction injury（CCI） of the sciatic nerve and on the expression of Fos protein in rats.Methods BoNT-A or vehicle was administered to the ispilateral side plantar surface of the hindpaw in male SD rats,which were prepared by CCI of the sciatic nerve to induce neuropathic pain.Mechanical and therml allodynia were observed before and on the 1st,3rd,5th,7th and 14th day after drug administration.The expression of Fos protein in the spinal dorsal horn was assessed by immunohistochemical method on the 5th day after drug administration.Results The rats of CCI group formed steady mechanical and heat hyperaglsia from the 7th day after operation to the end of this study.Administration of BoNT-A evidently increased paw mechanical withdrawal threshold（MWT）and thermal withdrawal latency（TWL） in the CCI rats.The expression of Fos protein was increased in CCI rats and BoNT-A 30 U/kg remarkably reduced the expression of Fos protein in the spinal cord.Conclusion Peripherally administration of BoNT-A reduces the expression of Fos protein in the spinal cord and remarkably suppresses mechanical allodynia and heat hyperalgesia of rats with neuropathic pain.