OBJECTIVE: To investigate the antinociceptive effect of intrathecal injection of snake venom analgesic fraction (AF) isolated from Naja tripudians on the neuropathic pain model rats, and to explore the effects of ATP-sensitive K* channel inhibitors on antinociceptive effect of AF. METHODS: L5 of left spinal nerve ligation and ectomy were conducted to establish neuropathic pain model rats. 50% paw withdrawal threshold (PWT) of bilateral hindfoot in model rats were determined within 24 h after different intrathecal dose of AF (0, 0.02, 0.04, 0.08 mg·kg-1'). Model rats were divided into control group, glybenclamide group (5 mg·kg-1), AF group (0.04 mg·kg-1) and drug combination group, and 50% PWT of bilateral hindfoot in those rats within 24 h after medication was investigated. RESULTS: Compared with before medication, 50% PWT of rats during 0.5 to 24 h after given 0.08 mg·kg-1 AF increased significantly (P<0.05), 50% PWT of rats during 1 to 6 h after given 0.04 mg-kg-1 AF increased significantly (P<0.05), 50% PWT of rats during 2 to 6 h after given AF increased significantly (P<0.05); compared with control group, 50% PWT of rats in glybenclamide group had no significant change, 50% PWT of rats in AF groups during 1 to 6 h after medication increased significantly (P<0.05); compared with AF group, 50% PWT of rats in drug combination group during 1 to 6 h after medication decreased significantly (P<0.05), and ipsilateral hindfoot wasn't significantly different from offside hindfoot CONCLUSION: Intrathecal injection of AF could relieve the neuropathic pain induced by peripheral nerve injury, and ATP-sensitive K.+ channel inhibitors can block antinociceptive effect of AF completely.%目的:研究鞘内注射眼镜蛇毒活性成分(AF)对病理性疼痛模型大鼠的镇痛作用,及三磷酸腺苷(ATP)敏感钾(KATP)通道阻滞药对其的影响.方法:采用左侧腰5脊神经结扎并切断,建立神经病理性疼痛模型大鼠；采用鞘内注射方法,考察给予不同剂量(0、0.02、0.04、0.08mg·kg-1)AF后24h内模型大鼠双侧后足的50％机械性撤足反应阈值(PWT).另将模型大鼠分为对照组、格列苯脲(5mg·kg-1)组、AF(0.04mg·kg-1)组及其联用组,考察各组大鼠给药后24h内双侧后足的50％PWT.结果:与给药前比较,给药后0.5～24h时段0.08mg·kg-1AF组大鼠的50％PWT明显增加(P＜0.05),给药后1～6h时段0.04mg·kg-1AF组大鼠的50％PWT明显增加(P＜0.05),给药后2～6h时段3个AF剂量组大鼠的50％PWT明显增加(P＜0.05)；与对照组比较,格列苯脲组50％PWT无明显变化,AF组1～6h时段50％PWT明显增加(P＜0.05)；与AF组比较,联用组给药后1～6h时段50％PWT明显减少(P＜0.05),且手术同侧后足与对侧后足比较无明显差异.结论:鞘内注射AF可缓解外周神经损伤引起的神经病理性疼痛,KATP通道阻滞药可完全阻断其镇痛作用.
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