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目的观察咪达唑仑和齐考诺肽对大鼠腰五脊神经结扎加切断(L5 SNL)引起的神经病理性疼痛的镇痛效应。方法取雄性SD大鼠64只,随机分为八组:L5 SNL模型组(L5 SNL组,生理盐水20μL)、齐考诺肽组(Z组,齐考诺肽30 ng)、咪达唑仑组(分M1、M2、M3三个亚组,分别给予咪达唑仑1、5、25μg)、联合治疗组(分Z+M1、Z+M2、Z+M3三个亚组,分别给予齐考诺肽30 ng+咪达唑仑1、5、25μg)。行为学测试检测大鼠给药前、后50%机械刺激撤足阈值(PWT)的变化,计算对应时间点的最大治疗效应百分比(MPE)。结果鞘内单次给予咪达唑仑1、5、25μg或齐考诺肽30 ng均可提高L5SNL大鼠的50%PWT和MPE(P<0.05或P<0.01),而联合使用咪达唑仑和齐考诺肽的镇痛效应显著大于两者单独用药(P<0.05);联合治疗组达到药效峰值的时间较咪达唑仑组缩短,维持时间较齐考诺肽组延长(P<0.05)。结论鞘内注射咪达唑仑和齐考诺肽均具有一定的抗神经病理性疼痛作用,而两药合用后镇痛效果更为显著。
Objective To observe the analgesic effects of midazolam and ziconotide on neuropathic pain induced by L5 SNL in rats. Methods Sixty-four male Sprague-Dawley rats were randomly divided into eight groups: L5 SNL model group (L5 SNL group, normal saline 20 μL), ziconotide group (Z group, ziconotide 30 ng), midazolam (Sub-groups M1, M2, and M3, midazolam 1,5 and 25 μg, respectively) and the combination therapy group (divided into three subgroups Z + M1, Z + M2 and Z + M3) 30 ng of kanamycin + midazolam 1,5, 25 μg). Behavioral test The changes of PWT in 50% of mechanical stimulation before and after administration were measured to calculate the maximum therapeutic effect percentage (MPE) corresponding to the time point. Results A single intrathecal administration of either midazolam at 1, 5, 25 μg, or ziconotide 30 ng increased 50% PWT and MPE in L5SNL rats (P <0.05 or P <0.01) The analgesic effect of Lun and ziconotide was significantly greater than that of both alone (P <0.05). The time to peak of pharmacodynamics in combination therapy group was shorter than that of midazolam group and prolonged <0.05). Conclusion Intrathecal injection of midazolam and ziconotide has some anti-neuropathic pain effect, and the two drugs combined analgesic effect is more significant.