Role and Mechanism of P2X7 Receptor in Trigeminal Neuralgia

doi:10.13701/j.cnki.kqyxyj.2025.11.004

Journal of Oral Science Research ›› 2025, Vol. 41 ›› Issue (11): 946-951.DOI: 10.13701/j.cnki.kqyxyj.2025.11.004

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Role and Mechanism of P2X7 Receptor in Trigeminal Neuralgia

QI Fang^1,2,3, JI Tuo^1,4, JIN Zhenshuai^1,4, WANG Li^1,4*

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

Abstract

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

QI Fang, JI Tuo, JIN Zhenshuai, WANG Li. Role and Mechanism of P2X7 Receptor in Trigeminal Neuralgia[J]. Journal of Oral Science Research, 2025, 41(11): 946-951.

References

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Role and Mechanism of P2X7 Receptor in Trigeminal Neuralgia

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