腹腔联合注射氯胺酮及可乐定对CCI模型大鼠的镇痛效应

摘要

Objective: To evaluate the analgesic effects of combined peritoneal injection of ketamine with clonidine on the chronic constriction injury (CCI) in rats. Methods: Sixty male SD rats were randomly divided into 5 groups as follows (n = 12): sham group (NS), NS group (S),ketamine group (K),clonidine group (CL) and combined group (KC). In group NS, the right sciatic nerves were exposed but not ligated, and in other groups four ligatures were placed around the right sciatic nerve according to the methods of Bennett. Rats in K group, CL group and KC group were intraperitoneally injected respectively with ketamine 10 mg/kg, clonidine 1 mg/kg and ketamine 5 mg/kg + clonidine 0.5 mg/kg daily at 3 ～14d after CCI. Rats in NS group and C group received the equal volume of saline. Mechanical and thermal pain thresholds were measured before operation and 3, 7, and 14 days after CCI. After pain thresholds, DRG of lumbar spinal was obtained from 4 randomized rats in each group to determine the GAP-43mRNA expression by RT-PCR. Results: Mechanical and thermal pain thresholds were significantly clecreased and GAP-43 mRNA of DRG expression were higher after CCI in group K, group CL, group KC and group NS than in group S ( P ＜ 0.05 ); Mechanical and thermal pain thresholds were significantly higher and GAP43mRNA of DRG expression in group KC, K and CL were lower after CCI than those in group C (P ＜0.05). Thermal and mechanical pain threshold increased and GAP-43mRNA of DRG expression decreased in group KC compared with those in group K and CL (P ＜ 0.05 ). Conclusion: Peritoneal injection of ketamine and clonidine can inhibit the development of mechanical allodynia and thermal hyperalgesia in the rat model of neuropathic pain, they can reduce the expression of GAP-43mRNA in rat and can also produce synergistic abirritation.%目的:研究氯胺酮及可乐定对慢性神经病理性疼痛模型大鼠的镇痛作用,并探讨其可能机制.方法:雄性SD大鼠60只,体重180～220g,随机分为假手术组(S组)、生理盐水组(NS组)、可乐定组(CL组)、氯胺酮组(K组)及氯胺酮+可乐定(KC组)组,每组12只.采用坐骨神经慢性压迫法(CCI)制备大鼠神经病理性痛模型,S组仅暴露坐骨神经,不结扎.K组、CL组和KC组于术后3～14d每天分别腹腔注射氯胺酮(10mg/kg)、可乐定(1m/kg)、氯胺酮(5mg/kg)+可乐定(0.5m/kg),S组和NS组腹腔注射等容量生理盐水.各组分别于术前、术后3、7、14d测定机械痛阈和热痛阈值,术后3、7、14d测定痛阈值后每组随机取4只大鼠断头处死,取腰段脊髓(L4～L6)背根神经节(DRG),采用逆转录PCR法(RT-PCR)检测GAP-43mRNA的表达水平.结果:与S组比较,NS组、K组、CL组和KC组术后机械痛阈和热痛阈降低,NS组、K组和CL组DRG中GAP-43mRNA表达上调,KC组仅在术后3d DRG中GAP-43mRNA表达上调(P＜0.05);与C组比较,K组、CL组和KC组术后机械痛阈和热痛阈升高,DRG中GAP-43mRNA表达下调(P＜0.05);与K组和CL组比较,KC组术后7、14d时机械痛阈和热痛阈升高,DRG中GAP-43mRNA表达下调(P＜0.05).结论:氯胺酮与一定剂量的可乐定联合应用能抑制神经病理性疼痛大鼠机械性触诱发痛和热痛觉过敏的形成,减少大鼠脊髓DRG中GAP-43mRNA的表达,具有显著的协同镇痛作用.