Enhanced RAGE Expression in the Dorsal Root Ganglion May Contribute to Neuropathic Pain Induced by Spinal Nerve Ligation in Rats
Enhanced RAGE Expression in the Dorsal Root Ganglion May Contribute to Neuropathic Pain Induced by Spinal Nerve Ligation in Rats
复制标题
背根神经节 RAGE 表达增强可能导致大鼠脊髓神经结扎引起的神经病理性疼痛
DOI：
10.1093/pm/pnv035
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发表时间：
2016-05-01
期刊：
影响因子：
3.1
通讯作者：
Yuan, Hongbin
中科院分区：
文献类型：
--
作者：
Li, Xiangnan;Yang, Haiqin;Yuan, Hongbin
目标。有证据表明晚期糖基化终产物受体(RAGE)信号与神经病理性疼痛(NP)的发病机制有关。目的是研究外周神经损伤后，背根神经节(DRG)中的RAGE信号是否参与了NP的发生。脊神经结扎术前后的实验研究。关在受控环境中。受试者。方法：雄性SD大鼠。采用SNL大鼠NP模型。通过对机械刺激(1.4~15g)的缩足阈值(PWT)来衡量机械痛敏。免疫荧光和免疫印迹法检测背根神经节RAGE、胶质纤维酸性蛋白(GFAP；卫星胶质细胞[SGC]激活标记物)、IL-1β(酶联免疫吸附试验)、肿瘤坏死因子-α(酶联免疫吸附试验)和核因子-kappaB(免疫印迹)的蛋白表达。鞘内注射抗RAGE抗体可抑制RAGE信号转导。7天后，SNL手术减少PWT，上调RAGE、GFAP、NF-kappaB、TNF-α和IL-1β的蛋白表达。鞘内注射RAGE中和抗体可减轻SNL诱导的机械痛觉过敏，减轻背根神经节内SGCs的激活，减轻背根节内核因子-kappaB、肿瘤坏死因子-α和IL-1β的表达。RAGE信号可能参与了大鼠SNL模型的痛过敏反应。虽然确切的机制仍未确定，但核因子-kappa B、肿瘤坏死因子-α和IL-1β可能与SGCs的激活一起发挥作用。
Objective. There is some evidence implicating receptor for advanced glycation end products ( RAGE) signaling in the pathogenesis of neuropathic pain (NP). The objective was to investigate whether RAGE signaling in the dorsal root ganglion ( DRG) might contribute to NP following peripheral nerve injury.Design. Experimental study before and after spinal nerve ligation (SNL) surgery.Setting. Caged in a controlled environment.Subjects. Male Sprague-Dawley rats.Methods. A SNL rat model of NP was used. Mechanical hyperalgesia was measured by the paw withdrawal threshold (PWT) to mechanical stimuli (1.4-15 g). Protein expressions of RAGE (immunofluorescence and western blotting), glial fibrillary acidic protein (GFAP; satellite glial cell [SGC] activation marker), IL-1 beta (ELISA), TNF-alpha (ELISA), and NF-kappa B (western blotting) in the DRG were determined. RAGE signaling was inhibited by intrathecal injection of anti-RAGE antibody.Results. After 7 days, SNL surgery reduced the PWT and upregulated the protein expression of RAGE, GFAP, NF-kappa B, TNF-alpha, and IL-1 beta. Intrathecal injection of RAGE-neutralizing antibody attenuated the SNL-induced mechanical hyperalgesia, activation of SGCs, and upregulation of NF-kappa B, TNF-alpha, and IL-1 beta in the DRG.Conclusion. RAGE signaling may contribute to the pain hypersensitivity observed in the rat SNL model of NP. Although the precise mechanism remains to be established, NF-kappa B, TNF-alpha, and IL-1 beta likely play a role, together with the activation of SGCs.