脊髓刺激术对神经病理性痛模型大鼠脊髓背角内NR2B受体和星形胶质细胞激活的影响

目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对L5脊神经结扎(spinal nerve ligation,SNL)诱导的神经病理性痛(neuropathic pain,NP)大鼠脊髓背角内NMDA受体亚单位NR2B的表达和星形胶质细胞激活的影响。方法:成年雄性SD大鼠48只,随机分为4组:正常组(不做任何处理);SCS组(植入SCS装置并给予SCS刺激);SNL+sham SCS组(给予SNL手术并植入SCS装置,但不进行刺激);SNL+SCS组(SNL手术并给予SCS刺激)。SCS刺激是在SNL术后第6～10 d进行(8 h/d),第10 d刺激结束后处死动物。运用行为学方法检测慢性痛状态下大鼠后肢对机械性刺激的反应阈值;采用免疫组织化学染色和Western blot方法分别检测脊髓背角内NR2B和星形胶质细胞的标志物GFAP的表达变化。结果:(1)SNL术后大鼠手术侧后足机械性痛敏显著增加,第6～10 d给予SCS刺激后,可观察到大鼠的痛行为学表现有明显缓解;(2)免疫组化结果显示:与SNL+sham SCS组相比,SNL+SCS组大鼠脊髓背角内NR2B和GFAP免疫阳性细胞的数量显著减少;(3)Western blot结果显示:给予SCS刺激后,SNL大鼠腰膨大段脊髓背角内NR2B的表达量显著下调,同时GFAP的表达量也明显有所降低。结论:给予SCS刺激可以有效地缓解SNL模型大鼠的神经病理性痛的行为学表现;该作用可能与SCS刺激抑制脊髓背角内NR2B的表达和星形胶质细胞的激活密切相关。

The effect of SCS on NR2B receptor and the activation of astrocytes in the spinal dorsal horn of rats with neuropathic pain

Objective: To investigate the effect of spinal cord stimulation(SCS) on NR2B subunit of the NMDA receptor and the activation of astrocytes in the spinal dorsal horn of rats with L5 spinal nerve ligation induced neuropathic pain(NP).Methods:48 adult male rats were divided into 4 groups randomly: normal group(normal rats without any operation);SCS group(normal rats planted with SCS devices,and received SCS stimulation),SNL+sham SCS group(rats were operated with SNL and were planted with SCS devices,but did not receive SCS stimulation),SNL+SCS group(SNL rats with SCS).During the 6th to 10th day after SNL operation,rats in SCS and SNL+SCS groups received SCS,8 h on every day.All the rats were sacrificed after SCS on the 10th day.Behavioral method was used to detect the hind paw withdraw threshold to mechanical stimulation for rats in neuropathic pain.Then,the expression change of NR2B and GFAP(the mark protein of astrocyte) in the spinal dorsal horn was observed via immunohisochemistry and Western blot methods respectively.Results:(1) The mechanical hyperalgesia of ipsilateral hind paw was increased significantly after SNL.After the SCS on 6~10 days,great relief of the rats ' pain behavior could be seen obviously;(2) The immunohistochemical staining results showed that NR2B and GFAP immunoreactive cells in the spinal dorsal horn reduced obviously in SNL+SCS group compared with SNL+sham SCS group;(3) Western blot results showed that the expression quantity of both NR2B and GFAP in the spinal dorsal horn of lumbar enlargement decreased significantly after SCS on SNL model rats.Conclusion: SCS could effectively alleviate the neuropathic pain behavior of SNL model rat.This effect may be closely related with the inhibition function of SCS to the expression of NR2B and the activation of astrocytes in the spinal dorsal horn.