米诺环素、氟代柠檬酸和B型酪氨酸激酶受体/Fc对维持期神经病理性疼痛大鼠脊髓背角脑源性神经营养因子表达的影响

目的:研究鞘内注射小胶质细胞抑制剂米诺环素、星形胶质细胞抑制剂氟代柠檬酸及脑源性神经营养因子(BDNF)清除剂B型酪氨酸激酶受体(TrkB)/Fc对神经病理性疼痛维持期大鼠的脊髓背角BDNF表达的影响,探讨BDNF在神经病理性疼痛维持期中的作用.方法:取36只成功鞘内置管大鼠,随机分为6组,每组6只:Ⅰ组为对照组,未行神经根结扎(SNL)术,未给药;Ⅱ组为SNL组;Ⅲ组为SNL+磷酸盐缓冲液组;Ⅳ组为SNL+米诺环素组,Ⅴ组为SNL+氟代柠檬酸组;Ⅵ组为SNL+TrkB/ Fc组.各组均于SNL术后7d鞘内给药,每日1次,连续5d.分别于SNL术前1h、首次给药前1h及末次给药前1h测定大鼠的50%机械缩爪阈值(50%PWT),并于末次给药后3h采用Western印迹法测定手术同侧脊髓背角的BDNF表达水平.结果:除Ⅰ组外,其他各组大鼠在SNL术后第7天的50%PWT均较术前1h显著降低(P值均<0.01).连续用药5d后,Ⅴ、Ⅵ组的50%PWT均较术后第7天显著升高(P值均<0.01),Ⅱ、Ⅲ、Ⅳ组维持期给药后脊髓背角BDNF表达水平显著高于Ⅰ组(P值均<0.01),Ⅴ、Ⅵ组显著低于Ⅱ组(P值均<0.01),结论:星形胶质细胞抑制剂氟代柠檬酸能显著抑制神经病理性疼痛维持期大鼠脊髓背角BDNF的过表达,进而缓解神经病理性疼痛,而小胶质细胞抑制剂米诺环素对维持期神经病理性疼痛大鼠的作用甚小.BDNF对神经病理性疼痛大鼠机械痛觉过敏的维持起重要作用,其机制可能与星形胶质细胞的活化有关.

Inhibitory effect of minocycline,fluorocitrate and tyrosine kinase receptor B/Fc against expression of spinal brain-derived neurotrophic factor during maintenance phase of neuropathic pain

Objective To investigate the effects of intrathecal injection of minocycline,fluorocitrate and tyrosine kinase receptor(Trk)B/Fc on expression of spinal brain-derived neurotrophic factor(BDNF) in rat dorsal horn during maintenance phase of neuropathic pain,so as to evaluate the role of BDNF in the maintenance of neuropathic pain.Methods Thirty six male Sprague-Dawley(SD) rats,weighing 200-260 g,were used in this study.After interthecal catheterization and left L5 spinal nerve ligation(SNL),animals were rand...