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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 被引量:4

EFFECTS OF DEXMEDETOMIDINE ON EXPRESSION OF PERK, PCREB, C-FOS IN SPINAL CORD IN RATS WITH NEUROPATHIC PAIN
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摘要 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.
出处 《中国疼痛医学杂志》 CAS CSCD 2015年第8期575-580,共6页 Chinese Journal of Pain Medicine
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