曲马多复合右美托咪定对神经病理性疼痛大鼠的镇痛效果研究

The analgesic effect of tramadol and dexmedetomidine in rats with neuropathic pain

目的研究曲马多复合右美托咪定对神经病理性疼痛所致大鼠认知功能障碍和内侧前额叶脑区NR2B表达的影响。方法 50只健康的雄性Wistar大鼠随机分为5组(每组10只),分别为假手术组(SO组),神经病理性疼痛模型组(NP组),模型注射曲马多组(T组),模型注射右美托咪定组(D组),模型注射曲马多+右美托咪定组(T+D组)。神经病理性疼痛模型采用左侧坐骨神经主干慢性压迫法制备。T组、D组和T+D组于术后3天开始分别每天尾静脉注射曲马多注射液(20 mg/kg)、右美托咪定(25μg/kg)、曲马多注射液(5 mg/kg)+右美托咪定(5μg/kg),SO组和NP组以等量生理盐水代替。各组大鼠分别于术后第3天、7天、10天和14天测右侧后足机械缩足阈(MWT)和热缩足潜伏期(TWL)。术后第14天,通过八臂迷宫实验检测大鼠的认知功能变化。八臂迷宫实验完成后立即处死大鼠,通过Western Blot方法检测内侧前额叶脑区NR2B表达水平。结果与SO组比较,NP组的术后痛阈明显降低(P<0.05),认知记忆能力明显降低(P<0.05),NR2B表达明显升高(P<0.05)。与T组和D组比较,T+D组的术后痛阈升高(P<0.05),认知记忆能力明显升高(P<0.05),NR2B表达明显下降(P<0.05)。结论曲马多复合右美托咪定的镇痛效果比单独应用曲马多或右美托咪定效果好,可改善大鼠NP导致的认知功能障碍并使内侧前额叶脑区NR2B表达降低。

Objective To evaluate the effect of tramadol and dexmedetomidine on cognitive impairment induced by neuropathic pain and NR2B expression level of medial prefrontal cortex in rats. Methods The 50 healthy male Wister rats were randomly divided into 5groups（ n = 10 in each group） ： sham operated group（ group SO）,neuropathic pain group（ group NP）,NP model injected with tramadol（ group T）,NP model injected with dexmedetomidine（ group D）,NP model injected with tramadol ＋ dexmedetomidine（ group T ＋ D）. The NP model of the chronic constriction injury of the sciatic nerve stem was used. Group T,group D and group T ＋ D were injected by tail vein with tramadol（ 20 mg / kg）,dexmedetomidine（ 25 μg / kg） and tramadol（ 5 mg / kg） ＋ dexmedetomidine（ 5 μg / kg） respectively once daily since the third day after operation. Mechanical withdrawal threshold（ MWT） and thermal withdrawal latency（ TWL） of right hind legs were measured on 3id,7th,10 th and14th day after operation respectively. On the 14 th day after operation,eight- arm radial maze task was carried out to investigate the effect of neuropathic pain on cognitive function in rats. Once the test was finished,rats were killed to measure the expression of NR2B protein in medial prefrontal cortex by Western Blotting methods. Results Compared with group SO,the pain threshold and the cognitive function was significantly decreased in group NP（ P〈0. 05）,while the NR2B expression level was significantly increased（ P〈0. 05）. Compared with group T and group D,the pain threshold and the cognitive function was significantly increased in group T ＋ D（ P〈0. 05）,while the NR2B expression level was significantly decreased（ P〈0. 05）. Conclusion The analgesic effect of tramadol and dexmedetomidine was better than that was used alone,they can relieve cognitive impairment induced by neuropathic pain and down- regulated the expression level of NR2B in medial prefrontal cortex.