基于神经元-星形胶质细胞间bFGF双重作用探讨电针治疗神经病理性痛的作用机制研究

Neuropathic pain (NP) is one of the most difficult clinical pain caused by the damage or disease of physical sensory system. Basic fibroblast growth factor (bFGF) , not only participates in the transmission of pain, but also plays an important role in the regulation of nervous system injury. Electro-acupuncture superimposed a variety of frequency pulse current to strengthen the stimulation and often used to treat pain. Based on our research before, we present the hypothesis that "the analgesia effect of electro-acupuncture is associated with astroglia P2RX7/MAPK/bFGF pathway and the repair effect of electro-acupuncture is associated with neuron A2A/cAMP/PKA/bFGF pathway ". Electro-acupuncture may inhibits the phosphorylation of p38MAPK by inhibiting astroglia P2RX7 expression, as a result, reduce the expression of bFGF to achieve the analgesic effect. Simultaneously, electro-acupuncture could promote the expression of A2A, A2A activates cAMP/PKA, and thus activates bFGF, reducing nerve damage and protecting neurons from damage or cell death. This study has important scientific significance for explaining the analgesic and repair effect of electro-acupuncture and promoting its clinical application.

神经病理性痛（NP）是由躯体感觉系统的损伤或疾病导致的疼痛。碱性成纤维细胞生长因子（bFGF）作为一个作用广泛的细胞因子，不仅能够参与疼痛的传导；同时也具有促神经再生和营养作用，在神经损伤修复过程中起重要作用。电针可叠加多种频率、模式的脉冲电流，常用于疼痛治疗。基于前期研究和文献调研，本课题提出“电针通过抑制星形胶质细胞P2X7/MAPK/bFGF通路抑制疼痛并通过激活神经元A2A/cAMP/PKA/bFGF通路促进修复”的假说。电针可能通过抑制星形胶质细胞P2X7受体表达，抑制p38MAPK磷酸化，减少bFGF的表达，达到镇痛作用。同时，电针能促进神经元内A2A表达，激活环磷酸腺苷-蛋白激酶A（cAMP/PKA），活化bFGF，参与神经修复。本课题对于阐释电针的镇痛效应及促神经修复的双重作用机制有重要科学意义。

神经病理性痛（NP）是由躯体感觉系统的损伤或疾病导致的疼痛。电针是叠加多种频率、模式的脉冲电流，常用于疼痛治疗。腺苷A2A受体与痛信息的传递和调控密切相关。A2A受体激活能够促进轴突延长以及树突树枝状延展，调节突触活动以及其他分子的突触动作。碱性成纤维细胞生长因子（bFGF）作为一个作用广泛的细胞因子，不仅能够参与疼痛的传导，同时也具有促神经再生和营养作用，在神经损伤修复过程中起重要作用。脊髓小胶质细胞激活是病理神经性疼痛发生和持续的关键因素，嘌呤能亚型P2X7受体参与了小胶质细胞介导的痛觉信息传导。本项目通过高尔基染色及电镜实验分别观察实验大鼠脊髓背角的神经元树突及突触情况，鞘内注射A2AR siRNA及腹腔注射A2AR拮抗剂、bFGF抑制剂探究电针促神经修复的分子机制，鞘内注射P2X7受体激活剂探究电针抗炎机制，为临床应用广泛且无创的电针的治疗效应及其机制提供实验依据。