大麻素受体1对坐骨神经结扎大鼠神经病理性疼痛的影响及机制  

Mechanism and Effects of Cannabinoid Receptor 1 on Sciatic Nerve Ligation-induced Neuropathic Pain in Rat Model

作　　者：李晓倩[1] 包娜仁[1] 张再莉[1] 马虹[1] 

机构地区：[1]中国医科大学附属第一医院麻醉科,沈阳110001

出　　处：《中国医科大学学报》2017年第3期205-209,共5页Journal of China Medical University

基　　金：国家自然科学基金(81601053);辽宁省教育厅科学研究项目(LK201636)

摘　　要：目的观察鞘内注射大麻素受体1(CB1)激动剂和拮抗剂对坐骨神经结扎大鼠行为学、痛阈以及脊髓组织中CB1表达的影响,探讨CB1在神经病理性疼痛中的作用及机制。方法 SD大鼠随机分为4组:假手术组(sham组)、坐骨神经结扎组(SNL组,鞘内注射30μL DMSO)、CB1激动剂组[AM841组,坐骨神经结扎前3 d鞘内注射5μg AM841(溶于30μL DMSO)]、CB1拮抗剂组[AM281组,坐骨神经结扎前3 d鞘内注射5μg AM281(溶于30μL DMSO)]。Sham组仅暴露坐骨神经而不结扎。其余各组均行右侧坐骨神经结扎术,术后1、3、5、7、10、14 d观察大鼠行为学变化,测定各组大鼠的热痛阈、机械性痛阈;Western blotting法检测脊髓组织中CB1表达。结果与sham组相比,SNL组术后各观察点大鼠逐渐出现术侧后肢足趾并拢、热痛觉过敏和机械异常性疼痛等症状,同时脊髓组织中CB1表达降低(P<0.05);AM841组脊髓CB1表达增加,抑制坐骨神经结扎所引起的热痛阈和机械性痛阈降低(P<0.05);AM281组脊髓CB1表达进一步降低、大鼠痛觉异常增大(P<0.05)。结论脊髓CB1参与神经病理性疼痛的调节,给予外源性大麻素CB1激动剂可以减轻坐骨神经结扎引起的神经病理性疼痛。Objective To observe the effects of intrathecal injection（IT）of agonist and antagonist of cannabinoid receptor 1 on pain threshold in rat model of sciatic nerve ligation（SNL）induced neuropathic pain,and investigate the role and mechanism of CB1 in neuropathic pain. Methods Male Sprague-Dawley rats were randomly divided into 4 groups：sham group（intrathecal normal saline,IT DMSO）,SNL group（SNL ＋ IT 30 μL DMSO）,AM841 group（SNL ＋ IT 5 μg AM841,dissolved in 30 μL of DMSO）and AM281 group（SNL ＋ IT 5 μg AM281,dissolved in 30 μL of DMSO）. IT was given 3 days before surgery. Sham group only had sciatic nerve exposure but without ligation. SNL model in the other three groups were established by right sciatic nerve ligation. The thermal and mechanical thresholds were assessed by paw withdrawal latency（PWL）to radiant heat and von Frey filaments at 1,3,5,7,10 and 14 days as well as behavior after SNL. Spinal expressions of CB1 were assessed by Western blotting. Results Compared with the sham group,symptoms of rats in SNL group,such as heat hyperalgesia,mechanical allodynia and posterior paws prone to close together,were gradually appeared in the observation time points,with lower spinal proteins expression of CB1（P 0.05）.AM841 group exhibited increased proteins expression of CB1 and inhibited SNL-induced heat hyperalgesia and mechanical allodynia（P 0.05）.AM281 group further decreased expression of CB1 and amplified the pain abnormality（P 0.05）. Conclusion Spinal CB1 participates in the regulation of neuropathic pain,and exogenous cannabinoid CB1 agonists can alleviate the SNL-induced neuropathic pain.

关 键 词：大麻素受体 神经病理性疼痛 脊髓 大鼠 

分 类 号：R741.02[医药卫生—神经病学与精神病学]