A型肉毒毒素调控钠离子通道Nav1.8缓解神经病理性疼痛的作用  

Analgesic Effect of Botulinum Neurotoxin Type A on Neuropathic Pain by Regulating Nav1.8 Sodium Channel

作　　者：陈曦[1] 郑淑慧[2] 胡昔权[1] 刘先国[3] 

机构地区：[1]中山大学附属第三医院康复医学科,广东广州510630 [2]中山大学附属第一医院转化医学研究中心,广东广州510080 [3]中山大学疼痛研究中心,广东广州510080

出　　处：《中山大学学报（医学科学版）》2014年第6期801-806,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：中央高校基本科研业务费专项资金(12ykpy45);广东省医学科研基金(B2013123;B2013113)

摘　　要：【目的】研究A型肉毒毒素(Bo NT/A)对腰5脊神经前根切断(L5 VRT)介导的神经病理性疼痛的影响,并进一步探讨其可能的内在作用机制。【方法】利用行为学测试方法观察Bo NT/A足底注射后对L5 VRT大鼠机械刺激撤足阈值的影响,采用Western blot方法分析Bo NT/A对L5 VRT术后背根神经节(DRG)神经元中钠离子通道(Nav1.8)蛋白表达的影响,并进一步应用全细胞膜片钳技术观察Bo NT/A对DRG神经元中功能性Nav1.8电流密度的影响。【结果】一侧足底注射7、15 U/kg的Bo NT/A 1 d后可显著缓解L5 VRT介导的机械触诱发痛症状,且作用时间至少持续至给药后14 d;Bo NT/A可显著下调L5 VRT术后DRG神经元中Nav1.8蛋白表达水平,并可明显降低功能性Nav1.8电流密度。【结论】Bo NT/A可能通过下调DRG神经元中Nav1.8蛋白表达,降低功能性Nav1.8电流,发挥缓解神经病理性疼痛的作用。[Objective] To investigate the analgesic effect of Botulinum Neurotoxin Type A （BoNT/A） on neuropathic pain induced by Lumbar 5 ventral root transaction （L5 VRT） and further to explain the underlying mechanism. [Methods] With use of the method of behavioral test, the effect of BoNT/A on the paw withdrawal threshold of L5 VRT rats was investigated, the effect of BoNT/ A on Nav l.8 protein expression in Dorsal Root Ganglion （DRG） neurons of L5 VRT rats was observed by Western blot, the functional Nav l.8 current density in DRG neurons was recorded with whole-cell patch clamp technique as well. [ Results ] Subplantar injection of BoNT/A at 7 U/kg and 15 U/kg in the ipsilateral hindpaw reversed LSVRT induced mechanical allodynia, started 1 day after injection and persisted for at least 14 days. Further experiments found that administration of BoNT/A down-regulated the Navl.8 expression and decreased the Navl.8 current density in DRG neurons significantly. [Conclusion] The reduetion of activity on the expression and function of Navl.8 sodium channel may contribute to the long-lasting analgestic effect of BoNT/A.

关 键 词：A型肉毒毒素 钠离子通道1.8 神经病理性疼痛 腰5脊神经前根切断 

分 类 号：R338.3[医药卫生—人体生理学]