【摘要】 目的探讨大鼠鞘内哇巴因及混合替扎尼定对神经病理性疼痛的治疗效能。方法雄性SD大鼠250～300g,鞘内留置PE-10导管,1周后制作大鼠脊神经结扎神经病理性疼痛模型。将大鼠随机分组:对照组、哇巴因组、替扎尼定组、哇巴因和替扎尼定混合药物组、育亨宾或阿托品拮抗组,每组6只。测定各组鞘内给药前、给药后各时点的大鼠机械撤足阈值,计算对应时点的最大效应百分比(%MPE),评价抗神经病理性疼痛效果。使用Isobologram分析评价药物的相互作用。结果大鼠鞘内单独注射哇巴因0.25～5μg和替扎尼定0.5～5μg产生剂量依赖性抗神经病理性疼痛的作用(P<0.05)。Isobologram分析显示大鼠鞘内哇巴因和替扎尼定混合物,两者产生明显的协同效应(P<0.05)。鞘内阿托品或育亨宾预处理,能够拮抗单独注射哇巴因2.5μg、替扎尼定5μg、哇巴因复合替扎尼定(1/2ED50)的作用(P<0.05)。结论大鼠鞘内单独注射哇巴因、替扎尼定产生剂量依赖性的抗神经病理性疼痛的作用;鞘内哇巴因混合替扎尼定产生协同作用,其机制可能与中枢α2-肾上腺素受体和胆碱能受体有关。更多还原

【Abstract】 Objective To investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats.Methods Male SD rats weighing 250-300 g were randomly divided into 5 groups(n=6), namely the control group, ouabain group, tizanidine group, combined ouabain and tizanidine injection group, and the antagonist group.Intrathecal catheter was implanted 7 days before spinal nerve ligation to establish the neuropathic pain model.Mechanical withdrawal threshold(MWT) before and after intrathecal administration of the agents was recorded in the rats.Isobolographic analysis was performed to evaluate the interactions between the agents.Result Intrathecal injection of ouabain(0.25-5 μg) or tizanidine(0.5-5 μg) alone produced dose-dependent analgesic effect against the neuropathic pain(P<0.05).Isobolographic analysis revealed a synergistic interaction between ouabain and tizanidine.Intrathecal pretreatment with atropine(5 μg) or yohimbine(20 μg) antagonized the effects of ouabain and tizanidine administered alone or in combination(P<0.05).Conclusion Intathecal injection of ouabain or tizanidine produces dose-dependent analgesic effects against neuropathic pain, and their synergistic effect after combined injection probably involves the cholinergic transmission and α2 receptor.更多还原