咪达唑仑联用齐考诺肽抗大鼠神经病理性疼痛的疗效评价  

Analgetic roles of intrathecally administerded midazolam combined with ziconotide in rat's neuropathic pain

作　　者：邓丽珍[1] 屠伟峰[1] 尹晴[1] 

机构地区：[1]广州军区广州总医院麻醉科,广东广州510010

出　　处：《中国新药与临床杂志》2013年第11期904-907,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：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。AIM To investigate the efficacy of intrathecally administrated midazolam and ziconotide in treating the neuropathic pain induced by 1-5 spinal nerve ligation （L5 SNL） in rats. METHODS Sixty- four male SD rats were randomly divided into eight groups： including L5 SNL model control group （L5 SNL group, 0.9%NS 20 μL）; ziconotide group （Z group, ziconotide 30 ng）; midazolam group （divided into M1, M2, M3 group, midazolam 1, 5, 25 μg） ; combination groups （divided into Z ＋ M1, Z ＋ M2, Z ＋ M3 group, ziconotide 30 ng ＋ midazolam 1 μg, 5 μg, 25 μg）. The 50% paw withdrawal threshold （PWT） was measured before and after the intrathecal administration. The changes of pain threshold and the maximum possible effect （MPE） were calculated to evaluate the analgetic efficacy of midazolam and ziconotide in relieving the neuropathic pain. RESULTS Compared with LSSNL group, the 50%PWT and MPE of M1, M2, M3, Z, Z ＋ M1, Z ＋ M2, Z ＋ M3 group were increased significantly （P 〈 0.05 or P 〈 0.01）. The combination groups were elevated more significantly than midazolam or ziconotide treated alone groups （P 〈 0.01 ）. Combination groups achieved the peak time of analgesic effect earlier than M1, M2 and M3 groups （P 〈 0.05）. Compared with the Z group, the maintenance of peak time were longer in combination groups （P 〈 0.05）. CONCLUSION Intrathecal bolus injections of midazolam or ziconotide could produce significant analgesic effects in neuropathic pain induced by L5 SNL in rats. Midazolzm combine with ziconotide are superior to midazolam or ziconotide alone for analgesic effects in neuropathic pain rats.

关 键 词：咪达唑仑 齐考诺肽 神经痛 镇痛 药物疗法 联合 

分 类 号：R338[医药卫生—人体生理学] R971[医药卫生—基础医学]