【摘要】 目的:探讨三叉神经痛动物模型中P2X7受体对疼痛信号传递及调节的作用机制。方法:采用眶下神经慢性缩窄性损伤(chronic constriction injury of the infraorbital nerve, CCI-ION)建立大鼠三叉神经痛模型。于术后第1、7、14、28天，通过检测头部退缩阈值评估机械性伤害感受；利用Western blot检测三叉神经尾侧亚核中P2X7受体的表达水平。此外，观察选择性P2X7受体拮抗剂A-804598对头部退缩阈值的影响，并通过Western blot分析三叉神经尾侧亚核中小胶质细胞活化标志物Iba1、磷酸化P38(p-P38)、白细胞介素-1β(interleukin-1β, IL-1β)和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)的水平。结果:CCI-ION后第1天，大鼠出现异常的痛觉过敏，且该状态持续到术后第28天。在CCI-ION后长达28 d的时间内，三叉神经脊束核中小胶质细胞活化明显，同时P2X7受体、p-P38、TNF-α及IL-1β均呈激活并且呈现上调状态。P2X7受体选择性拮抗剂A-804598可阻断CCI-ION诱导的异常痛觉过敏，同时抑制小胶质细胞活化及炎症因子的上调。结论:P2X7受体激活可促进小胶质细胞释放炎症因子，对三叉神经痛痛觉超敏的启动与维持具有关键作用。以P2X7受体介导的神经炎症为靶点，可能成为治疗三叉神经痛的新策略。更多还原

【Abstract】 Objective: To investigate the mechanism by which P2X7 receptors regulate pain signal transmission in an animal model of trigeminal neuralgia. Methods: A rat model of trigeminal neuralgia was established using chronic constriction injury of the infraorbital nerve(CCI-ION). On day 1, 7, 14, and 28 after surgery, mechanical nociception was evaluated by measuring the head withdrawal threshold. Western blotting was used to detect the expression level of P2X7 receptors in the caudal subnucleus of the trigeminal nerve. Additionally, the effect of the selective P2X7 receptor antagonist A-804598 on the head withdrawal threshold was observed, and Western blotting was performed to analyze the levels of microglial activation marker Iba1, phosphorylated P38(p-P38), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in the caudal subnucleus of the trigeminal nerve. Results: On day 1 after CCI-ION, rats developed allodynia/hyperalgesia, which persisted until day 28. Within 4 weeks after CCI-ION, significant microglial activation was observed in the trigeminal spinal tract nucleus, accompanied by increased activation and upregulation of P2X7 receptors, p-P38, TNF-α, and IL-1β. The selective P2X7 receptor antagonist A-804598 blocked CCI-ION-induced allodynia/hyperalgesia, while inhibiting microglial activation and the upregulation of inflammatory factors. Conclusion: Activation of P2X7 receptors promotes the release of inflammatory factors by microglia, playing a key role in the initiation and maintenance of hyperalgesia in trigeminal neuralgia. Targeting P2X7 receptor-mediated neuroinflammation may represent a novel strategy for the treatment of trigeminal neuralgia.更多还原