目的探讨钙通道拮抗剂维拉帕米对静脉全麻药氯胺酮拮抗神经病理性疼痛的影响。方法 48只健康♂大鼠随机分为正常对照组(N)、假手术组(S)、疼痛模型组(M)、氯胺酮给药组(K)、维拉帕米给药组(V)以及维拉帕米和氯胺酮联合给药组(V+K)共6组,通过大鼠坐骨神经松扎制备坐骨神经慢性缩窄性损伤(CCI)神经病理性疼痛模型。各组大鼠从手术后d1~14每天腹腔注射相应不同的药物,N、S和M组大鼠给予生理盐水,K组大鼠给予10μg.g-1的氯胺酮溶液,V组大鼠给予5μg.g-1的维拉帕米溶液,V+K组先给予维拉帕米(5μg.g-1)溶液,20 min后再给予氯胺酮溶液。在手术前1 d和手术后1、3、7、11 d和14 d给药后10 min分别用Hargreaves法测量热缩足潜伏期,VonFrey细丝测量机械刺激缩足反射阈值。结果在手术前各组之间的痛觉无差异,在手术和给药后各时间点模型组大鼠的热缩足潜伏期和机械刺激缩足反射阈值均降低,而氯胺酮改善了CCI大鼠的热痛觉过敏和机械痛觉超敏,维拉帕米单独给药对CCI大鼠的痛觉无影响,但联合用药时维拉帕米增强了氯胺酮的镇痛效应。结论维拉帕米能够增强氯胺酮拮抗CCI大鼠神经病理性疼痛的作用。
Aim To observe the effect of verapamil on antagonistic action of ketamine on neuropathic pain in rats.Methods 48 male rats were randomly divided into 6 groups: normal control group(N),sham operation group(S),model group(M),ketamine group(K),verapamil group(V) and verapamil combined with ketamine group(V+K).The neuropathic pain model of rats was established by sciatic nerve chronic constriction injury(CCI).The rats were administered every day with different drugs by intraperitoneal injection from the first day to the fourteenth day after operation.The rats in N,S and M groups were administered with normal saline.The rats in K group were administered with ketamine(10 μg·g-1).The rats in V group were administered with verapamil(5 μg·g-1).The rats in V+K group were firstly administered with verapamil(5 μg·g-1),and ketamine 20 minutes later.On first day before operation and the first,third,seventh,eleventh,fourteenth day after operation ten minutes after administration,Hargreaves method and VonFrey method were used to measure thermal withdrawal latency(TWL) and mechanical withdrawal threshold(MWT).Results The algesthesia of rats in every group before operation had no significant difference.At different time points after operation and administration the TWL and MWT of rats in model group were markedly decreased.Ketamine significantly prolonged TWL and elevated MWT of CCI rats.Although verapamil alone didn't significantly affect the TWL and MWT of CCI rats,the analgesic effects of ketamine were markedly enhanced by verapamil.Conclusion Verapamil can significantly enhance the antagonistic action of ketamine on neuropathic pain in CCI rats.