氯胺酮和可乐定联合应用对大鼠慢性神经病理性痛的影响

Effect of combined injection of ketamine and clonidine on the chronic neuropathic pain in rats

目的:观察腹腔联合应用氯胺酮和可乐定对大鼠慢性神经病理性疼痛的影响。方法:雄性SD大鼠80只,体重180—220g,随机分为假手术组(S组)、对照组(C组)、氯胺酮组(K组)、可乐定组(CL组)和联合组(KC组),每组16只。S组大鼠仅分离坐骨神经但不结扎,其余组建立坐骨神经慢性压迫性损伤(CCI)模型,K、CL、KC组分别于术后3d开始至取材点每天腹腔注射氯胺酮10mg/kg、可乐定1mg/kg和氯胺酮5mg/kg+可乐定0.5mg/kg。S组和C组注射相同体积的生理盐水。各组大鼠取4只分别于术前1天,术后第3天、第7天、第14天、第21天测定大鼠机械性缩足痛阈(MWT)和热缩爪潜伏期(TWL)。结果:与术前及S组比较,C组、K组、CL组、KC组术后3d开始TWL及MWT显著降低(P<0.05);与C组比较,K组、CL组、KC组第7天,第14天,第21天TWL及MWT显著升高(P<0.05);与K组和CL组比较,KC组的TWL及MWT显著升高(P<0.05)。结论:氯胺酮及可乐定均具有明显的镇痛效应,联合用药可对抗神经病理性痛大鼠的痛觉过敏反应,对防治中枢神经敏感化的形成和发展有一定作用,具有临床应用潜能。

Objective：To observe the effect of combined intraperitoneal injection of ketamine and clonidine for chronic neuropathic pain in chronic constriction injury（CCI） rats.Method：Eighty male SD rats weighing 180—220g were randomly divided into 5 groups as follows（n=16 each）：sham operation group（S）,CCI group（C）,ketamine group（K）,clonidine group（CL） and combined group（KC）.In group S,the right sciatic nerves were exposed but not ligated,and in other groups four ligatures were placed around the right sciatic nerve according to Bennett＇s method.From the 3rd d after operation,10 mg/kg ketamine,1 mg/kg clonidine and 5 mg/kg ketamine ＋ 0.5mg/kg clonidine were injected intraperitoneally into group K,CL and KC daily and respectively and the same volume normal saline was injected into group S and C.Mechanical and thermal pain threshold were measured by paw withdrawal latencies to von Frey hair and radiant heat stimulation at 1d before operation and at the end of the 3rd,7th,14th,21th d after operation.Result：Thermal withdrawal latency（TWL） and mechanical withdrawal threshold（MWT） of group C,K,CL and KC markedly reduced at the end of the 3rd d after operation compared with those before operation and with group S（P0.05）.TWL shortened most significantly at the end of the 3rd d;However,MWT dropped most significantly at the end of the 7th d after operation（P0.05）.TWL and MWT of group K,CL,KC at the end of the 7th,14th,21th d after operation increased compared with that of group C（P0.05）,and the most remarkable effect appeared at the 21st d after operation.TWL and MWT of group KC was significantly higher than that of group K and CL（P0.05）.Conclusion：Ketamine and clonidine all showed evident analgesic effects.The combined injection of ketamine and clonidine can reduce hyperalgesia and the administration in combination may provide better effect.