口腔医学研究

口腔医学研究 ›› 2025, Vol. 41 ›› Issue (11): 946-951.DOI: 10.13701/j.cnki.kqyxyj.2025.11.004

• 口腔颌面外科学研究 • 上一篇    下一篇

P2X7受体在三叉神经痛中的作用与机制研究

齐芳1,2,3, 季拓1,4, 金振帅1,4, 王丽1,4*   

  1. 1.口颌系统重建与再生全国重点实验室,口腔生物医学教育部重点实验室,口腔医学湖北省重点实验室 湖北 武汉 430079;
    2.武汉大学口腔医院光谷分院口腔舒适化治疗中心 湖北 武汉 430200;
    3.武汉大学口腔医院光谷分院麻醉科 湖北 武汉 430200;
    4.武汉大学口腔医院麻醉科 湖北 武汉 430079
  • 收稿日期:2025-08-25 出版日期:2025-11-28 发布日期:2025-11-25
  • 通讯作者: *王丽,E-mail:kq000682@whu.edu.cn
  • 作者简介:齐芳(1991~ ),女,湖北荆州人,硕士,主治医师,研究方向:疼痛的神经生物学机制研究。
  • 基金资助:
    湖北省自然科学基金面上项目(编号:2025AFB536)

Role and Mechanism of P2X7 Receptor in Trigeminal Neuralgia

QI Fang1,2,3, JI Tuo1,4, JIN Zhenshuai1,4, WANG Li1,4*   

  1. 1. State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
    2. Oral Comfort Treatment Center at Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan 430200, China;
    3. Department of Anesthesiology at Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan 430200, China;
    4. Department of Anesthesiology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China
  • Received:2025-08-25 Online:2025-11-28 Published:2025-11-25

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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。

关键词: P2X7受体, 神经病理性疼痛, 小胶质细胞, 细胞因子

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.

Key words: P2X7 receptor, neuropathic pain, microglia, cytokines