转运蛋白在背根神经节参与调控神经病理性疼痛的机制研究

THE INVOLVEMENT OF TRANSLOCATOR PROTEIN IN THE DORSAL ROOT GANGLION IN NEUROPATHIC PAIN

目的:探讨背根神经节(dorsal root ganglion,DRG)转运蛋白(translocator protein,TSPO)对神经病理性疼痛(neuropathic pain,NP)的影响及可能的作用机制。方法:雄性SD大鼠随机分为3组:假手术组(Sham组)、对照组(SNI组)和给药组(Ro组)。采用von-Frey丝测量大鼠50%机械刺激缩足阈值(paw withdrawal threshold,PWT),在术后第7天、14天取DRG,采用免疫荧光及蛋白印迹技术检测TSPO、脑源性神经营养因子BDNF和蛋白激酶p-ERK。结果:(1)相较Sham组,SNI组DRG表达TSPO阳性细胞升高(D7:P<0.05,D14:P<0.01),TSPO在DRG与肽能和非肽能中小神经元、有髓大神经元和卫星胶质细胞均有共定位。(2)SNI组大鼠PWT术后相较Sham组明显降低(P<0.01);Ro组大鼠鞘内注射Ro5-4864后PWT升高(D7:P<0.01,D14:P<0.05)、BDNF下调(P<0.05)、p-ERK1(P<0.01)和p-ERK2(D7:P<0.01,D14:P<0.05)下降。结论:鞘内注射TSPO配体Ro5-4864可缓解NP大鼠的痛觉超敏,其在DRG的机制可能与抑制p-ERK、BDNF的活化有关。

Objective： To investigate the role of translocator protein（TSPO） in the dorsal root ganglion（DRG） in neuropathic pain and to explore the possible mechanism. Methods： All male Sprague-Dawley rats were randomly assigned into 3 groups： the Sham group, the control group（SNI group） and the treatment group（Ro group）. Vonfrey filaments were used to measure the 50% paw withdrawal thresholds（PWT）. The expression of TSPO, BDNF and p-ERK in the DRG was detected by western blot and immunofluorescence. Results：（1） Compared with the Sham group, the expression of TSPO was increased in the SNI group（D7： P 〈 0.05, D14： P 〈 0.01）. The TSPO signals were colocalized with IB4, CGRP, NF-200 positive neurons and S-100 positive glial cells.（2） The PWT of SNI rats was significantly decreased compared with the sham group（P 〈 0.01）, which was reversed by intrathecal injection of ligand of TSPO（Ro5-4864）（D7： P 〈 0.01, D14： P 〈 0.05）. Furthermore, the expression of BDNF（P 〈 0.05）, p-ERK1（P 〈 0.01） and p-ERK2（D7： P 〈 0.01, D14： P 〈 0.05） was declined in the Ro group. Conclusion： A single intrathecal injection of TSPO agonist Ro5-4864 attenuated mechanical allodynia in neuropathic pain. The mechanisms may be partly attributed to the inhibition of p-ERK and BDNF expression in the DRG.