可乐定对慢性神经病理性痛大鼠背根神经节GAP-43mRNA表达的影响

Effect of intraperitoneal clonidine on expression of GAP-43 mRNA in spinal cord in a rat model of chronic neuropathic pain

目的 探讨可乐定对慢性神经病理性痛大鼠生长相关蛋白（GAP-43）mRNA表达的影响。方法雄性成年SD大鼠36只，体重180～220g，随机分为假手术组（S组）、慢性压迫性损伤组（CCI组）和可乐定组（CL组），每组12只。采用结扎坐骨神经法制备慢性压迫性损伤模型，S组仅暴露坐骨神经，不结扎。CL组于坐骨神经结扎术后3～14d每天腹腔注射可乐定1mg／kg。S组和CCI组腹腔注射生理盐水1ml。于术前、术后3、7、14d时测定机械痛阈和热痛阈，术后3、7、14d测定痛阈后随机取4只大鼠断头处死，取腰段脊髓（L4-6）及背根神经节，采用RT—PCR法检测GAP-43mRNA的表达水平。结果与S组比较，CCI组和CL组术后机械痛阚和热痛阈降低，背根神经节GAP-43mRNA表达上调（P〈0．05）；与CCI组比较，CL组术后7、14d时机械痛阈和热痛阈升高，背根神经节GAP-43mRNA表达下调（P〈0．05）。结论坐骨神经结扎术后3～14d每天腹腔注射可乐定1mg／kg可有效减轻大鼠慢性神经病理性痛，其机制可能与其抑制背根神经节GAP-43mRNA表达上调有关。

Objective To evaluate the effect of intraperitoneal （IP） clonidine on the expression of GAP-43 mRNA in the spinal cord in a rat model of chronic neuropathic pain. Methods Thirty-six male SD rats weighing 180-220 g were randomly assigned to one of 3 groups （ n = 12 each） ： group Ⅰsham operation （S） ; group Ⅱ chronic constriction injury （CCI） and group Ⅲ IP clonidine ＋ CCI （CL）. The animals were anesthetized with IP 10% chloral hydrate 300 mg/kg. The fight sciatic nerve was exposed and 4 ligatures were placed in group CCI and CL. Clonidine 1 mg/kg was given IP immediately after surgery in group CL. Paw-withdrawal threshold （PWT） to thermal and yon Frey filament stimulation was measured before （To , baseline） and at 3, 7 and 14 days after surgery （T1.3）. The animals were then killed. The lumbar segment of the spinal cord was removed for determination of the expression of GAP-43 mRNA. Results The PWT to thermal and mechanical stimulation was significantly reduced at 3 days after surgery （T1） in group CCI and CL as compared with group S, and was significantly higher at T2 and T3 in group CL than in group CCI. The GAP-43 mRNA expression in the spinal cord was significantly increased in group CCI and CL as compared with group S and significantly lower in group CL than in group CCI. Conclusion Intraperitoneal clonidine can inhibit hyperalgesia by reducing the expression of GAP-43 mRNA in the spinal cord in a rat model of chronic neuropathic pain.