大麻素抑制坐骨神经损伤导致的神经痛及脊髓背角HCN4通道表达

Inhibition of neuropathic pain and HCN4 channels expression in spinal dorsal horn of sciatic nerve injured rats by cannabinoid

目的:观察CB1受体在坐骨神经缩窄性损伤(CCI)所致的神经痛中的作用及对CCI大鼠脊髓背角HCN4通道表达的影响。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电子测痛仪测定各组大鼠损伤侧机械缩足阈值(MWT);免疫印迹法检测损伤侧L_4~L_6脊髓背角HCN4的表达。结果:CCI术后1~14 d大鼠MWT明显降低,呈现稳定的机械痛敏;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);预先给予CB1受体拮抗剂AM251(0.05 mg/kg)可明显阻断CP55940的镇痛效果(P<0.05)。免疫印迹检测结果显示,CCI大鼠损伤侧L_4~L_6脊髓背角HCN4通道表达明显增加(P<0.05);鞘内给予CP55940可显著降低CCI大鼠的HCN4表达(P<0.05),CP55940抑制HCN4表达的效应可被AM251阻断(P<0.05)。结论:脊髓CB1受体激活对外周神经损伤导致的神经痛具有良好的镇痛作用,其镇痛效应可能与抑制神经痛大鼠脊髓背角HCN4通道表达有关。

Objective： To investigate the role of cannabinoid receptor1（ CB1R） in sciatic chronic constriction injury（ CCI） induced neuropathic pain and its effect on hyperpolarization-activated cyclic nucleotide-gated（ HCN） channels 4 expression in spinal dorsal horn. Methods： 7 ~ 8 weeks old SD rats were divided into 4 groups：（ 1） sham group;（ 2）CCI group;（ 3） CP55940 ＋ CCI group;（ 4） AM251 ＋ CP55940 ＋ CCI group. Mechanical withdrawal threshold（ MWT）were measured by electric von Frey pain detector. The expression of HCN4 channels was detected by Western Blot.Results： MWT of CCI rats was significantly lower than that in the sham group on 1 ~ 14 d after nerve injury（ P〈0. 05）.Intrathecal administration of CP55940（ 0. 05 mg/kg）,cannabinoid receptors agonist,markedly inhibited the decrease of MWT after CCI（ P〈0. 05）. Intrathecal administration of AM251（ 0. 05 mg/kg）,CB1R antagonist,markedly blocked the analgetic effect of CP55940. The expression of HCN4 channels in the injured L4,L5 and L6 dorsal spinal cord was markedly enhanced after CCI（ P〈0. 05）. Intrathecal administration of CP55940 dramaticlly inhibited the increase of HCN4 channels expression after CCI. The inhibitory effect of CP55940 was blocked by CB1R antagonist AM251（ P〈0. 05）. Conclusion： Activation of CB1R has analgesic effect to neuropathic pain induced by peripheral nerve injury.CB1R＇s analgesia may be related to its inhibition of HCN4 channels expression in dorsal spinal cord.