A型肉毒毒素对神经病理性疼痛大鼠钠离子通道Nav1.3和钠电流的影响  

The effect of botulinum neurotoxin type A on Nav1.3 sodium channels and sodium currents in animals modeling neuropathic pain

作　　者：陈曦[1] 杨雨菡 蔡庆[1] 梁森 胡昔权[1] Chen Xi;Yang Yuhan;Cai Qing;Liang Sen;Hu Xiquan(Department of Rehabilitation Medicine,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院康复医学科,广州510630

出　　处：《中华物理医学与康复杂志》2020年第9期769-774,共6页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：国家自然科学基金面上项目(81871849);国家自然科学基金青年基金项目(81301674)。

摘　　要：目的探讨A型肉毒毒素(BoNT/A)对神经病理性疼痛大鼠背根神经节(DRG)神经元中钠通道Nav1.3和功能性钠电流的影响。方法建立保留性神经损伤(SNI)病理性疼痛模型,将造模成功大鼠根据注射溶液的不同按随机数字表法分为生理盐水注射组(注射生理盐水)和BoNT/A注射组(注射BoNT/A),每组9只;另取9只大鼠设为假手术组,只分离暴露坐骨神经分支,但不做神经结扎手术。术后第5天在一侧足底皮下注射BoNT/A(7 U/kg和15 U/kg)或等量的生理盐水,检测注射后不同时间点(给药后第3天、第7天和第14天)大鼠机械撤足阈值的变化。采用Western Blot检测观察给药后第7天和第14天BoNT/A对各组大鼠DRG神经元中Nav1.3蛋白表达的影响,用电生理膜片钳检测BoNT/A对各组大鼠功能性河豚毒素敏感型(TTX-S)钠电流的影响。结果足底皮下注射BoNT/A可显著升高外周神经损伤后下降的机械触痛阈(P<0.001),缓解神经病理性疼痛。SNI术后DRG神经元中Nav1.3蛋白表达明显上调(P<0.001),BoNT/A干预后第7天和第14天的Nav1.3蛋白表达显著下调(P<0.01);BoNT/A可降低SNI术后增大的TTX-S钠电流(P<0.05)。结论BoNT/A可调控Nav1.3钠通道蛋白表达,影响功能性TTX-S钠电流,发挥改善神经病理性疼痛的作用。Objective To investigate the effect of botulinum neurotoxin type A(BoNT/A)on Nav1.3 sodium channels and the function of sodium current in neuropathic pain.Methods Eighteen adult rats had a spared nerve injury(SNI)induced and then were randomly divided into a saline group and a BoNT/A group,each of 9.Another 9 rats formed a fake operation group,Five days after the SNI,BoNT/A(7U/kg or 15U/kg)or saline was subcutaneously administered into the plantar surface of a hindpaw.On the 3rd,7th and 14th day after the injection,the SNI rats′paw withdrawal threshold was measured.On the 7th and 14th day the expression of Nav1.3 protein in dorsal root ganglion(DRG)neurons was examined using western blotting,while any change in the functional tetrodotoxin-sensitive(TTX-S)current was recorded using the patch clamp technique.Results Administration of BoNT/A at either 7U/kg or 15U/kg significantly increased the SNI-induced mechanical allodynia.The expression of Nav1.3 protein in DRG neurons increased significantly after the SNI,but had decreased significantly by the 7th and 14th day after the administration of BoNT/A.BoNT/A significantly decreased the current density in TTX-S sodium channels in DRG neurons following SNI.Conclusion Administration of BoTN/A affects the expression of Nav1.3 protein and functional TTX-S current,relieving neuropathic pain.

关 键 词：外周神经损伤 神经病理性疼痛 A型肉毒毒素 钠通道 背根神经节 

分 类 号：R741[医药卫生—神经病学与精神病学]