腹腔注射右美托咪啶对神经病理性疼痛大鼠镇痛的实验研究

EFFECTS OF DEXMEDETOMIDINE ON EXPRESSION OF PERK, PCREB, C-FOS IN SPINAL CORD IN RATS WITH NEUROPATHIC PAIN

目的：评价右美托咪啶对神经病理性疼痛大鼠行为学、痛敏及脊髓背角神经元磷酸化胞外反应激酶（phosphorylated extracellular regulated protein kinases,pERK）、磷酸化cAMP反应元件结合蛋白（phosphorylated cAMP response element bound protein,pCREB）、c-fos蛋白表达的影响.方法：健康成年雄性Wistar大鼠54只,6～8周龄,体重180～220 g,采用随机数字表法,将其分为3组（n=18）：假手术组（S组）、慢性神经病理性疼痛组（C组）和右美托咪啶组（D组）.S组仅分离坐骨神经但不结扎,C组和D组采用结扎坐骨神经的方法制备大鼠坐骨神经慢性压迫性损伤（chronic constriction injury,CCI）的神经病理性疼痛模型,D组于术后即刻开始至处死前1d腹腔注射右美托咪啶50 μg/kg,1次/d,S组和C组注射等容量生理盐水.于术前1d、术后3、7、14d时以缩足阈值（paw withdrawal threshold,PWT）测定大鼠机械痛阈和辐射热的缩足潜伏期（paw withdrawllatency,PWL）测定大鼠的热痛阈,并于术后测定痛阈后灌注处死大鼠,取L4～6脊髓组织,采用免疫组织化学法检测脊髓背角神经元pERK、pCREB、c-fos的表达水平.结果：与S组比较,C组和D组术后3、7、14 d时MWT降低,TWL缩短,脊髓背角pERK、pCREB、c-fos表达上调（P＜0.05）;与C组比较,D组术后3、7、14 d时MWT升高,TWL延长,脊髓背角pERK、pCREB、c-fos表达下调（P＜0.05）.与术前1d比较,C组和D组术后3、7、14d时MWT降低,TWL缩短;与术后3d时比较,C组和D组7、14d时MWT降低,TWL缩短,脊髓背角pERK、pCREB、c-fos表达上调（P＜0.05）.结论：右美托咪啶可减轻大鼠慢性神经病理性疼痛,抑制pERK、pCREB、c-fos的表达可能是其作用机制之一.

Objective： To investigate the effects of dexmedetomidine （Dex） on expression of pERK, pCREB, c-fos in spinal dorsal horn in rats with neuropathic pain （NP）. Methods： Fifty-four adult, male, Wistar rats weighing 180-220 g were randomly divided into 3 groups （n=18）： sham operation group （group S）, chronic constriction injury group （group C） and dexmedetomidine group （group D）. The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg. Four ligatures were made on right sciatic nerve at 1 mm intervals with 4-0 silk thread in group C and group D. In group D, Dex （50 μg/ kg） was injected intraperitoneally once a day starting from the end of operation until the animals were sacrificed. 50% paw withdrawal threshold （PWT） to mechanical stimulation with von Frey filament and paw withdrawal latency to thermal stimulation （TWL） were measured on the preoperative 1 d, 3, 7 and 14 days after operation. Animals of three groups were killed at each time points after the measurement of PWT and TWL. The lumbar segments （L4-6） were removed for measuring the expression of pERK, pCREB, c-fos by immunohistochemistry. Results： CCI significantly decreased PWT and PWL, increased the expressionof pERK, pCREB, c-fos on the 3rd, 7th and 14th day in spinal dorsal horn in group C and group D compared with group S. Intraperitoneal injection of DEX significantly attenuated CCI-induced mechanical and thermal hyperalgesia in group D as compared with group C. Intraperitoneal injection of DEX suppressed the expression of pERK, pCREB and c-fos in group D compared with group C. Conclusion： Intraperitoneal injection of DEX can reduce the chronic neuropathic pain in rats, possibly through inhibiting the expression of pERK pCREB and c-fos in spinal dorsal horn.