氟吡汀对神经病理性疼痛大鼠的镇痛作用及其机制研究

ANALGESIC EFFECTS OF FLUPIRITINE ON SPINAL NERVE LIGATION-INDUCED NEUROPATHIC PAIN IN RATS

目的：探讨钾离子通道开放剂氟吡汀对神经病理性疼痛大鼠的镇痛作用及交感芽生的影响,为神经病理性疼痛药物治疗提供理论依据.方法：成年雄性SD大鼠18只,体重250～350 g,按随机数字表法随机分为3组,每组6只：假手术组（S组）,对照组（C组）,氟吡汀组（F组）.S组大鼠暴露腰5 （L5）脊神经,但不结扎.其余组大鼠暴露L5脊神经并结扎,建立疼痛模型.S组和C组大鼠腹腔注射生理盐水2 ml/kg,F组大鼠腹腔注射氟吡汀5mg/kg,并连续给药7d.各组大鼠术前3d及术后1、3、5、7d检测机械痛阈（paw withdrawal pressure threshold,PWPT）和缩足反射潜伏期（paw withdrawal latency,PWL）.术后第7d,各组大鼠取手术侧L5背根神经节采用免疫荧光染色标记法检测背根神经节内篮状结构变化.结果：与S组比较,C组大鼠PWPT和PWL术后第1d起显著降低（P＜0.05）,维持至术后第7d.与C组比较,F组大鼠术后第3d起PWPT和PWL明显提高,差异有统计学意义（P＜0.05）.与C组比较,经过氟吡汀治疗后,F组大鼠术后第7d手术侧L5背根神经节内篮状结构显著减少（P＜0.05）.结论：氟吡汀通过抑制背根神经节内交感芽生以减轻神经病理性疼痛.

Objective：To investigate the effects of flupirtine on neuropathic pain and sympathetic sprouting in the dorsal root ganglion of rats after spinal nerve ligation （SNL）.Methods：18 healthy adult male Sprague-Dawley rats weighing 250 ～ 350 g were randomly divided into three groups with six rats in each group,including sham group （group S）,control group （group C） and flupirtine group （group F）.The neuropathic pain model was established by the L5 spinal nerve ligation.In group S,the L5 spinal nerve was exposed but not ligated.In group C and F,the L5 spinal nerve was exposed and ligated.The rats in group S and C received saline 2 ml/kg and the rats in group F received flupirtine 5 mg/kg via intraperitoneal injection daily for seven days after the surgery.Pain threshold was estimated by measuring paw withdrawal pressure threshold （PWPT） and latency （PWL） 3 days before surgery （baseline） and 1,3,5,7 days after surgery.The rats were sacrificed on the 7th day after surgery and the L5 dorsal root ganglion of all rats were collected to observe the change of basket formation by immunofluorescent staining.Results：PWPT and PWL in group C were significantly lower than those in group S within 1 ～ 7 days after surgery （P ＜ 0.05）.Compared with group C,the PWPT and PWL in group F were significantly improved from the third day after surgery （P ＜ 0.05）.After flupirtine treatment,the number of basket formation in the L5 dorsal root ganglion of the operated side was prominently decreased compared with group C on the 7th day （P ＜ 0.05）.Conclusion：Flupirtine may relieve neuropathic pain by reducing sympathetic fiber sprouting within dorsal root ganglion.