目的:研究曲马多对神经病理性痛(neuropathic pain,NP)大鼠的镇痛作用及对脊髓背角N-甲基-D-天门冬氨酸(N-Methyl-D-Aspartate,NMDA)受体NR2B亚基表达的影响。方法:雄性wistar大鼠,随机分为3组(每组10只):假手术组(Sham operation,SO组)、NP模型组(NP组)、曲马多处理组(Tramadol组,T组)。NP模型采用慢性坐骨神经压迫损伤的方法制作。各组大鼠分别于术前和术后3、7、10、14 d测术侧后爪机械缩足阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal latency,TWL)。T组于术后3 d开始腹腔注射曲马多注射液(20 mg/kg),术后14 d取大鼠脊髓背角用免疫荧光法与RT-PCR方法检测NR2B蛋白和mRNA表达水平。结果:与SO组比较,NP组术后痛阈明显降低,NR2B表达水平明显升高(P〈0.05)。与NP组比较,T组术后痛阈升高,NR2B表达水平明显降低(P〈0.05)。T组和SO组比较,痛阈和NR2B表达水平差异无统计学意义。结论:曲马多可反转NP模型脊髓背角的NR2B表达上调并具有镇痛作用。
Objective: To investigate effects of tramadol on neuropathic pain (NP) and NR2B expression level in spinal dorsal horn (SDH) in NP rats. Methods: Male Wistar rats were randomly divided into 3 groups (n = 10 in each group): sham operation group (SO group), neuropathic pain group (NP group), tramadol group (T group). The rat model of NP was established by operation of chronic constriction injury of the sciatic nerve. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of each group were measured on the preoperative and postoperative 3rd, 7th, 10th and 14th day. T group was injected intraperitoneally with tramadol (20 mg/kg) on the 3rd - 14th day after the operation, once daily. On the 14th day after the operation, NR2B protein and mRNA expression levels in SDH were evaluated by immunofluorescence assay and RT-PCR respectively. Results: Compared with SO group, the postoperative pain threshold was decreased significantly and the NR2B protein expression level was obviously increased in NP group (P 〈 0.05). Compared with the NP group, the postoperative pain threshold was significantly increased and the NR2B protein expression level significantly reduced in T group (P 〈 0.05). There was no significant difference in pain thresholds and the NR2B protein expression level between T group and SO group. Conclusion: Tramadol has analgesic action and reverses the up-regulated expression of NR2B in SDH induced by NP.