氯胺酮与可乐定对神经病理性痛大鼠脊髓P2X4R mRNA表达的影响

目的 评价氯胺酮与可乐定对神经病理性痛大鼠脊髓P2X4受体mRNA(P2X4R mRNA)表达的影响.方法 雄性SD大鼠80只,体重180～220 g,随机分为假手术组(S组)、神经病理性痛组(NP组)、氯胺酮组(K组)、可乐定组(CL组)和氯胺酮+可乐定组(KC组),每组16只.采用坐骨神经慢性压迫(CCI)法制备大鼠神经病理性痛模型.K组、CL组、KC组于CCI后3～21 d每天分别腹腔注射氯胺酮10 mg/kg、可乐定1 mg/kg和氯胺酮5 mg/kg+可乐定0.5 mg/kg.S组和NP组腹腔注射等容量生理盐水.分别于CCI前1 d、CCI后3、7、14和21 d且腹腔注射前,随机取4只大鼠,测定机械痛阈和热痛阈,并于CCI前1 d、CCI后7、14和21 d痛阈测定结束后断头处死,测定脊髓P2X4R mRNA表达水平.结果 与CCI前1 d比较,CCI后S组热痛阈、机械痛阈和脊髓P2X4R mRNA表达差异无统计学意义(P>0.05),其余4组热痛阈和机械痛阈降低,脊髓P2X4R mRNA表达上调(P<0.05);与NP组比较,K组、CL组、KC组CCI后热痛阈及机械痛阈升高,脊髓P2X4R mRNA表达下调(P<0.05);与K组比较,KC组CCI后热痛阈和机械痛阈升高,脊髓P2X4R mRNA表达下调(P<0.05),CL组上述指标差异无统计学意义(P>0.05).结论 氯胺酮与可乐定减轻大鼠神经病理性痛的机制可能与下调脊髓P2X4R mRNA的表达有关.

Effect of ketamine and cionidine on P2X4 R mRNA expression in spinal cord in a rat model of neuropathic pain

Objective To evaluate the effect of ketamine and elonidine on P2X4R mRNA expression in the spinal cord in a rat model of neuropathic pain.Methods Eighty male SD rats weighing 180-220 g were randomly divided inte 5 groups (n = 16 each): sham operation group (group S),neuropathic pain group (group NP),ketamine group (group K),clonidine group (group CL) and ketamine + clonidine group (group KC).The animals were anesthetized with intraperitoneal chloral hydrate 400 mg/kg.The right sciatic nerve was exposed and four ligatures were placed on the sciatic nerve at 1 mm interval.In group S,the right sciatic nerve was exposed but not ligated,and in the other groups four ligatures were placed around the right sciatic nerve (chronic constrictive injury,CCI) as described by Bennett.The animals were injected intraperitoneally with ketamine 10 mg/kg,clonidine 1 mg/kg,and ketamine 5 mg/kg + clonidine 0.5 mg/kg in normal saline 2 ml in group K,CL and KC respectively,while normal saline 2 ml in group S and NP at 3-21 d after CCI.Mechanical and thermal pain threshold were measured by paw withdrawal latencies to run Frey hair and radiant heat stimulation at 1 d before and 3,7,14,21 d after CCI.Four animals were killed at 1 d before (baseline) and 7,14 and 21 d after CCI following the measurement of pain threshold in each group and the L4.5 segments of the spinal cord were removed for determination of P2X4 R mRNA expression by RT-PCR.Results There was no significant change in thermal and mechanical paln threshold and P2X4 R mRNA expression in the spinal cord after CCI in group S ( P > 0.05),while thermal and mechanical pain threshold was reduced,and P2X4 R mRNA expression was up-regulated in the other four groups as compared with the baseline values (P < 0.05 ).Thermal and mechanical pain threshold was significantly higher and P2X4 R mRNA expression in the spinal cord lower after CCI in group K,CL and KC than in group NP ( P < 0.05 ).Thermal and mechanical pain threshold was significantly higher and P2X4 R mRNA expression lower after CCI in group KC than in group K ( P < 0.05),but no significant difference was found in the above parameters between group CL and K ( P > 0.05).Conclusion Both ketamine and clonidine can alleviate neuropathic pain via down-regulating the expression of P2X4 R mRNA in the spinal cord in a rat model of neuropathic pain.