脊髓小胶质细胞抑制对神经病理性痛大鼠脊髓背角GABAB受体表达的影响

目的 通过观察鞘内注射特异性小胶质细胞抑制剂米诺环素对神经病理性痛大鼠脊髓背角GABAB受体表达的影响,探讨脊髓小胶质细胞活化介导神经病理性痛发生的作用机制.方法 雄性SD大鼠48只,体重220～260 g,结扎L5神经根制备神经病理性痛模型,随机分为4组(n=12):Ⅰ组仅暴露L5神经根但不结扎,鞘内注射生理盐水10 μl;Ⅱ组暴露并结扎L5神经根,鞘内注射生理盐水10 μl;Ⅲ组仅暴露L5神经根但不结扎,鞘内注射米诺环素50 μg(10μl);Ⅳ组暴露并结扎L5神经根,鞘内注射米诺环素50 μg(10 μl).于术前1 d～术后18 d,每日鞘内注射生理盐水或米诺环素,2次/d.于术前1 d(基础状态)、术后1、2、4、6、8、10、12、14、16、18 d各组取6只大鼠测定机械痛阈,并确定机械痛周最低点,然后在机械痛阈最低点时各组另取6只大鼠测定脊髓背角GABABR2的表达.结果 与Ⅰ组相比,Ⅱ组机械痛阈降低,术侧脊髓背角GABABR2表达下调(P＜0.05或0.01);与Ⅱ组和Ⅲ组比较,Ⅳ组机械痛阈升高,术侧脊髓背角GABABR2表达上调(P＜0.05或0.01).结论 脊髓小胶质细胞活化介导神经病理性痛发生的作用机制可能与抑制GABAB受体的激活有关.

Effect of microglia inhibition on GABAB receptor expression in the spinal cord in a rat model of neuropathic pain

Objective To investigate the effects of minocycline,a selective microglia inhibitor on dorsal GABAB receptor expression in the spinal cord in a rat model of neuropathic pain and the possible mechanism.Methods Forty-eight male SD rats weighing 220-260 g were used in this study.Neuropathic pain was induced by ligation of L5 spinal nerve(SNL).The animals were randomly divided into 4 groups(n=12 each):Ⅰ sham operation;Ⅱ SNL;Ⅲ sham operation+intrathecal(IT)minocycline 50 μg;IV SNL+IT minecycline 50 μg.Paw withdrawal threshold to von Frey hair stimulation was measured before operation(baseline)and at post-surgery days 1,2,4,6,8,10,12,14,16,18 in 6 animals in each group.The GABABR2 expression in dorsal horn of spinal cord was detected by Western blot at the time point when paw withdrawal threshold to mechanical stimulation was the lowest in another six animals which did not undergo yon Frey hair stimulation test.Results The paw withdrawal threshold to mechanical stimuli and the GABABR2 expression in the dorsal horn of spinal cord were significantly lower in SNL group than in sham operation group.The decreased paw withdrawal threshold to von Frey hair stimulation and the down-regulated GABABR2 expression in the spinal cord induced by SNL were ameliorated by intrathecal administration of micmglia inhibitor- minocycline in group Ⅳ.Conclusion The mechanism of neuropathic pain mediated by microglia activation may be related to the inhibition of GABAB receptor activation.