脊髓与背根神经节细胞外信号调节蛋白激酶5(ERK5)信号通路在神经病理性疼痛中的作用的大鼠模型实验

目的 探讨脊髓与背根神经节(DGR)细胞外信号调节蛋白激酶5(ERK5)信号通路在神经病理性疼痛中的作用。方法 选取SD大鼠通过坐骨神经结扎(CCI)建立神经病理性疼痛模型,对建模1、3、6 d脊髓与背根神经节p-ERK5进行免疫组化染色,分析其表达水平变化情况; 利用反义寡核苷酸技术并结合免疫印迹和免疫组化检测DGR中ERK5和p-CREB表达水平的变化; 分析鞘内注射反义寡核苷酸对CCI 大鼠机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)的影响。结果 SD大鼠神经病理性疼痛模型建立后p-ERK5阳性神经节数量显著增加; 鞘内注射ERK5反义寡核苷酸可有效抑制脊髓与背根神经节ERK5的表达,同时可上调p-CREB的表达; 大鼠机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)均明显下降。结论 脊髓与背根神经节ERK5可能在神经病理性疼痛过程中具有重要调节作用,并且ERK5通过CREB相关基因的表达来发挥其部分功能

The role of extracellular signaling regulatory protein kinase 5(ERK5)signaling pathway in neuropathic pain of spinal cord and dorsal root ganglion in rat model experiment

ObjectiveTo analyze the role of extracellular signaling regulatory protein kinase 5(ERK5)signaling pathway in neuropathic pain of spinal cord and dorsal root ganglion(DGR)in rat model experiment.Methods SD rats were selected to establish the neuropathic model by means of sciatic nerve ligation(CCI). Immunohistochemical staining was performed on p-ERK5 of spinal cord and dorsal root ganglion on the 1, 3, and 6^th day after modeling, and the expression level changes were analyzed. The changes of ERK5 and p-CREB expression levels in DGR were detected by using antisense oligonucleotide technology combined with western blot and immunohistochemistry. The effects of intrathecal injection of antisense oligonucleotides on mechanical foot reflex threshold(MWT)and thermal foot reflex latency(TWL)in CCI rats were analyzed.Results After the establishment of SD rat neuropathic model, the number of p-ERK5 positive ganglion increased significantly. Intrathecal injection of ERK5 antisense oligonucleotides could effectively inhibit the expression of ERK5 in spinal cord and dorsal root ganglion, and up-regulate the expression of p-CREB. The mechanical foot reflex threshold(MWT)and thermal foot reflex latency(TWL)of rats were significantly decreased.Conclusion Spinal cord and dorsal root ganglion ERK5 played an important role in the regulation of neuropathic pain, and ERK5 played a part of its functions through the expression of CREB-related genes.