CB_1受体对坐骨神经损伤导致的神经痛及背根节HCN2通道表达的调节作用  

The role of cannabinoid receptor 1 in neuropathic pain and HCN2 channels expression in dorsal root ganglion induced by sciatic nerve injury

作　　者：陈美云 雷晓露 孙涛 马彦巧 曾俊伟 余德芊 刘晓红 

机构地区：[1]遵义医学院基础医学院生理学教研室,遵义563000

出　　处：《神经解剖学杂志》2018年第1期67-71,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31360253)

摘　　要：目的:观察大麻素CB_1受体在坐骨神经缩窄性损伤(CCI)所致的神经痛中的作用及其对背根节HCN2通道表达的调节。方法:7~8周龄SD大鼠分为4组:(1)Sham组(假手术组);(2)CCI组;(3)CP55940+CCI组;(4)AM251+CP55940+CCI组。采用von Frey测痛仪测定各组大鼠神经损伤侧机械缩足阈值(MWT);免疫印迹技术检测损伤侧L_4~L_6背根节HCN2通道表达。结果:CCI术后1 d即形成稳定的机械痛敏,MWT降低;鞘内给予大麻素受体激动剂CP55940(0.05 mg/kg)可显著升高CCI大鼠MWT(P<0.05);预先鞘内注射CB_1R拮抗剂AM251(0.05 mg/kg)可明显阻断CP55940的镇痛效果(P<0.05)。免疫印迹实验结果显示,CCI大鼠损伤侧L_4~L_6背根节CB_1受体、HCN2通道表达明显增加(P<0.05);鞘内给予CP55940可显著降低HCN2表达(P<0.05),AM251可明显抑制CP55940降低HCN2表达的效应(P<0.05)。结论:背根节CB_1受体激活对CCI所致的神经痛具有良好的镇痛作用,其镇痛效应可能与抑制CCI大鼠背根节HCN2通道表达有关。Objective： To investigate the role of cannabinoid receptor 1 （ CB- R） in neuropathic pain induced by sciatic chronic constriction injury （CCI） and its effect on the expression of hyperpolarization-activated cyclic nucleotide-gated （HCN） channels 2 in dorsal root ganglion. Methods： SD rats （7 - 8 weeks old） were divided into 4 groups. （1） sham group ; （2） CCI group ; （3） CP55940 ＋ CCI group; （4） AM251 ＋ CP55940 ＋ CCI group. Mechanical withdrawal threshold （MWT） was measured. The expression of HCN2 channels was detected by Western Blot. Results： MWT of CCI rats was significantly lower than that in the sham group （P 〈 0.05）. Intrathecal administration of CP55940 （0.05 mg/kg）, cannabinoid receptors agonist, markedly inhibited the decrease of MWT after nerve injury （ P 〈 0.05 ）. Intrathecal administration of AM251 （0.05 mg/kg）, CBIR antagonist, markedly blocked the analgesic effect of CP55940. The expression of CBI R and HCN2 channels in the injured IA, L5 and L6 dorsal root ganglion markedly enhanced on 7 d （P 〈 0.05 ） and 14 d （P 〈 0.05 ） after CCI. Intrathecal administration of CP55940 dramaticlly inhibited the increase of HCN2 channels expression after CCI. The inhibitory effect of CP55940 was blocked by AM251 （P 〈 0.05）. Conclusion： Activation of CB1R has analgesic effect on neuropathic pain induced by CCI. The analgesic effect of CB2 R may be related to its inhibition of HCN2 channels expression in dorsal root ganglion.

关 键 词：神经病理性疼痛 大麻素受体 背根神经节 HCN通道 

分 类 号：R745.4[医药卫生—神经病学与精神病学]