鞘内注射维生素B_6对大鼠慢性神经痛的镇痛作用及对DRG神经元p-ERK表达的影响

目的:观察维生素B_6(VitB_6)对神经病理性疼痛大鼠机械痛敏、热痛敏及L4～L5背根神经节(DRG)磷酸化细胞外信号调节激酶(P-ERK)表达的影响.方法:选择6只正常SD大鼠作为对照组(control),另选择鞘内置管3天后无神经损伤症状的SD雄性大鼠54只,随机分为3组(n=18):假手术组(sham):只分离坐骨神经;CCI组:结扎坐骨神经;CCI+Vit B6组:坐骨神经结扎后鞘内注射VitB_610mg/kg/d,连续两周.各组术前2天和术后1、3、5、7、10、14天测定各组大鼠热缩足反射潜伏期(TWL)、机械缩足反射阈值(MWT).除control组外其余各组分别在术后3d、7d和14d处死大鼠,采用免疫组织化学法观察L4～5 DRG和p-ERK的表达.结果:与sham组比较,CCI组术后各天TWL、MWT明显降低(P＜0.01);与CCI组比较,CCI+VitB_6组术后3、5、7、10、14天TWL明显增高(3天P＜0.05,5、7、10、14天P＜0.01),而术后各天MWT无明显差别.术后3、7、14天,CCI组结扎侧L4,5背根节p-ERK阳性细胞率明显高于sham组(P＜0.01),CCI+Vit B_6组结扎侧L4,5背根节p-ERK阳性细胞率明显低于CCI组(P＜0.01).结论:背根神经节ERK活化参与神经病理性疼痛信号传递,鞘内注射Vit B_6抑制CCI大鼠热痛敏,其机制可能包括通过上游机制抑制ERK激活.

EFFECTS OF INTRATHECAL ADMINISTRATION OF VlTAMINE B6 ON THE NEUROPATHIC PAIN IN RATS WITH LIGATION OF SCIATIC NERVE AND THE EXPRESSION OF p-ERK IN DRG NEURONS

Objective:To investigate the effect of vitamine B_6 (Vit B_6) on neuropathic pain and the expression of p-ERK in L4,5 DRG in CCI rats.Methods:6 SD rats were used as control group without any operation,another 54 male SD rats,which showed no signs of never injury 3 days after IT catheterization with the tip of catheter reaching the lumbar region,were randomly divided into 3 groups ( n = 18 ): Sham,CCI and CCI + Vit B_6 group.CCI + Vit B_6 group was treated with intrathecal injection Vit B_6 for two weeks.Thermal withdrawal latency(TWL) and mechanical withdrawal threshold(MWT) of the rats were measured on 1,2 pre-operative and 1,3,5,7,10,14 post-operative days.The expression of p-ERK of ipsilateral L4,5 DRG were assessed by immunohistochemistry on 3,7,14 post-operative days.Results:TWL and MWT in CCI group were significantly lower than sham group on every post-operative day (P ＜0.01 );TWL in CCI + Vit B_6 group was higher than CCI group on 3,5,7,10,14 post-operative days(P ＜0.05 on 3 postoperative day,P ＜ 0.01 on 5,7,10,14 postoperative days),there was no significant difference in MWT between the two groups.The increase of the percentage of immunoreactive p-ERK neurons in the ipsilateral L4,5 DRG in CCI group was evident at 3,7,14d after surgery compared with those of the sham group ( P ＜0.01 ).The intrathecal injection of Vit B_6 markedly suppressed the increase of CCI induced p-ERK expression.Conclusion:ERK activation in dorsal root ganglion may contribute to the transmission of neuropathic pain,Vit B_6 can alleviate thermal hyperalgesia induced by CCI,the mechanism may include inhibiting ERK activation from its upper stream.