褪黑素的镇痛作用及对哌替啶镇痛作用的影响

摘要

目的 研究褪黑素(MT)的镇痛作用及其与哌替啶(PD)联合使用的效果.方法 将60只昆明小鼠随机平均分为对照组、MT1组(40 mg/kg)、MT2组(80 mg/kg)、MT3组(160 mg/kg)、PD组(40 mg/kg)和联合注射组(MT80 mg/kg、PD 40 mg/kg).每只小鼠腹腔注射1.2mL药物.30 min后用Von Frey测痛法测定小鼠两后足的痛阈值.对上述对照组、MT2组、MT3组、PD组和联合注射组小鼠再连续5d给药并每天测痛,观察药物镇痛作用的耐受性.继续给药ld后,立即注射纳洛酮,观察小鼠的戒断反应.同时,每天统计小鼠排便数量,观察药物对胃肠道的影响.结果 MT1、MT2、MT3组与对照组相比,褪黑素有明显镇痛作用,并呈剂量依赖性.MT2组与PD组镇痛效果差异无统计学意义(P＞0.008 7),MT3组镇痛效果高于PD组(P＜0.0087).褪黑素和PD的联合使用使镇痛效果有所提高.褪黑素组和PD组小鼠均产生了耐受性,但褪黑素组小鼠耐受性小于PD组(P＜0.05).PD组小鼠出现显著戒断反应,而褪黑素组、联合注射组及对照组小鼠未出现明显戒断反应(P＞0.05). PD组小鼠排便数量显著高于对照组(P＜0.05).褪黑素组和联合注射组小鼠排便与对照组无显著差异.结论 褪黑素镇痛作用显著,与PD有协同作用,具有一定的耐受性但不产生依赖性,并可以逆转PD的依赖性和胃肠道副作用.这为褪黑素在镇痛方面的开发研究提供了动物学实验依据.%Objective To study the analgesic effects of melatonin (MT) and its joint administration with pethidine (PD). Methods Totally 60 Kunming mice were randomly divided into six groups: control group, MT1 (40mg/kg) group, MT2 (80 mg/kg) group, MT3 (160 mg/kg) group, PD (40 mg/kg) group and the combined injection (MT 80 mg/kg, PD 40 mg/kg) group, with 15 in each group. Half an hour after intraperitoneal injection of 1. 2 mL drug was given to each mouse, the pain threshold of the hind feet was determined by Von Frey dolorimeter. Then all the groups except MT1 group were given the medication for five consecutive days. Meanwhile pain was measured and the tolerance of the drugs' analgesic effect was observed each day. After another day's injection, naloxone was injected immediately and withdrawal reactions were observed. The times of defecation were recorded daily to observe the effect of the drugs on the gastrointestinal tract. Results MT had a significant analgesic effect in a dose-dependent manner. The analgesic effect of MT (80 mg/kg) and PD (40 mg/kg) was not significantly different (P>0. 0087), but the joint use of MT and PD obviously increased the analgesic effect. Tolerance presented in MT groups and PD group, but was lower in MT groups (P<0.05). A significant withdrawal reaction occurred in PD group (P<0.05), but not in MT groups, the combined injection group or control group (P>0.05). The times of defecation were significantly higher in PD group than in the control group (P<0.05) and were almost the same in the other groups. Conclusion MT has an obvious analgesic effect and a synergic effect with PD. It produces certain tolerance but no dependence, and can reverse the physical dependence and gastrointestinal side effects of PD. Our study has provided animal experiment evidence for research on development of MT as an analgesic.