TRPV1受体参与脊髓电刺激对外周伤害性信息传递的抑制作用  

The role of TRPV1 receptors in the suppression of nociceptive transmission induced by spinal cord stimulation in rats with neuropathic pain

作　　者：王培培[1] 杨菲 WANG Pei-Pei;YANG Fei(Department of Neurobiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院神经生物学系,北京100069 [2]首都医科大学人脑保护高精尖中心,北京100069

出　　处：《中国疼痛医学杂志》2020年第1期20-26,共7页Chinese Journal of Pain Medicine

基　　金：北京市教育委员会-北京市自然基金联合资助项目（3500-11920625）;科技创新服务能力建设-高精尖中心-人脑保护高精尖创新中心（市级）（3500-11920117）

摘　　要：目的:脊髓电刺激(spinal cord stimulation,SCS)可以有效缓解临床上的神经病理性疼痛症状,但其镇痛机制尚不清楚。本研究利用大鼠脊神经损伤神经病理性疼痛模型和在体电生理技术,探讨脊髓TRPV1受体在SCS所引发的脊髓背角伤害性信息传递抑制中的作用。方法:36只成年雄性SD大鼠,行左侧L5脊神经结扎剪断术(spinal nerve ligation,SNL),造模后3~4周时随机分成两批各18只进行在体电生理实验。第一批18只分成三组用于记录脊髓背角浅层的局部诱发场电位(local field potential,LFP):SCS+vehicle组(n=6),SCS+AMG9810组(TRPV1拮抗剂,脊髓表面给药,50 mg/100μl,n=6),SCS+RTX组(TRPV1激动剂,背根神经节注射,200 ng/10μl,n=6);第二批18只分成三组用于记录脊髓背角深层的广动力范围(wide dynamic range,WDR)神经元:SCS+vehicle组(n=6),SCS+AMG9810组(n=6),SCS+RTX组(n=6)。观察SNL模型中SCS对脊髓节段伤害性传递是否起到抑制作用,以及使用AMG9810阻断TRPV1或RTX清除外周TRPV1对这种抑制作用的影响。结果:给予5 min 50 Hz的SCS可以显著抑制LFP中的C纤维诱发场电位(C-fiber evoked field potential,C-LFP),而局部给予AMG9810能够部分阻断SCS的抑制作用,在RTX处理后的大鼠中SCS无法抑制C-LFP。同样参数的SCS也可以显著抑制WDR神经元的C纤维成分,但是给予AMG9810或RTX处理没有减弱SCS对WDR神经元的抑制作用。结论:在脊髓背角,特别是外周神经末梢上的TRPV1受体参与了SCS对脊髓背角浅层伤害性信息传递的抑制,但没有参与SCS对脊髓背角深层伤害性信息传递的抑制。Objective:By using the rat model of spinal nerve ligation(SNL)and in vivo electrophysiology,we investigated the role of spinal TRPV1 receptors in the suppression of nociceptive transmission in the spinal dorsal horn induced by spinal cord stimulation(SCS).Methods:Thirty-six adult male Sprague-Dawley rats were used for the left L5 SNL model.After 3-4 weeks of ligation,they were randomly divided into two batches for electrophysiological experiments.The first batch of rats were divided into three groups for the recording of C-fiber-induced field potential(C-LFP)in the superficial dorsal horn of spinal cord:SCS+vehicle(n=6),SCS+AMG9810(TRPV1 antagonist,spinal cord surface application,50 mg/100μl,n=6),SCS+RTX(TRPV1 agonist,DRG injection,200 ng/10μl,n=6);The second batch of rats were divided into three groups for recording the wide dynamic range(WDR)neurons in the deep spinal dorsal horn:SCS+vehicle(n=6),SCS+AMG9810(n=6),SCS+RTX(n=6).Results:SCS(50 Hz,5 min)significantly inhibited C-LFP.The administration of AMG9810 or RTX blocked the inhibitory effect of SCS.SCS with the same parameters also significantly inhibited the C-fiber component of WDR neurons,but AMG9810 and RTX did not attenuate the inhibitory effect of SCS on WDR neurons.Conclusion:The TRPV1 receptor in spinal dorsal horn,especially on the terminal of primary afferent fibers participates in the inhibition of SCS on the superficial nociceptive transmission in the dorsal horn,but does not get involved in the inhibition of SCS on the nociceptive transmission in the deep dorsal horn.

关 键 词：脊髓电刺激 神经病理性疼痛 TRPV1受体 C纤维诱发场电位 广动力范围神经元 

分 类 号：R741[医药卫生—神经病学与精神病学]