Jujuboside A Alleviates Facial Allodynia of CCI ‐ ION Rats by Inhibiting the Expression of P2X7 Receptor in the Spinal Trigeminal Subnucleus Caudalis

Background Trigeminal neuralgia is a common neuropathic pain of the oral and maxillofacial region. P2X7 receptor, a neural mediator, P2X7 receptor is closely related to this condition. Despite several studies on the role of Jujuboside A in sleep, few reports are available on its effects on chronic neuropathic pain. Methods In this study, a rat trigeminal neuralgia model was established by chronic constriction injury of the infraorbital nerve. Rats were intervened with Jujuboside A and P2X7 shRNA. For the behavioral aspect, the changes in the facial mechanical pain withdrawal threshold of the rats were measured. Molecular biology techniques such as Western Blotting, Real‐Time Quantitative PCR, Immunohistochemistry and Enzyme‐Linked Immunosorbent Assay were used to determine the changes in the P2X7 receptor, pyroptosis pathway, and inflammatory factors. Results The facial mechanical withdrawal threshold showed a significantly greater reduction in the trigeminal neuralgia group than in the sham group at 14 days post‐operation. Jujuboside A therapy could alleviate the facial allodynia and inhibit the up‐regulation of P2X7 expression in the spinal trigeminal subnucleus caudalis. Additionally, the expression of P2X7, nucleotide‐binding domain, leucine‐rich family, and pyrin domain‐containing 3 caspase‐1 and interleukin‐1β was significantly greater in the trigeminal neuralgia group than in the sham group, suggesting activation of the pyroptosis cascade; this could be reversed by Jujuboside A application. Moreover, Jujuboside A administration downregulated the phosphorylation of ERK1/2 in the spinal trigeminal subnucleus caudalis of the trigeminal neuralgia group. Molecular docking demonstrated a high binding force between Jujuboside A and P2X7. Furthermore, the P2X7 knockdown treatments effectively increased the facial mechanical withdrawal threshold of trigeminal neuralgia rats. Conclusion These findings suggest the potential benefits of Jujuboside A in trigeminal neuralgia treatment through suppression of pyroptosis by inhibition of the nucleotide‐binding domain, leucine‐rich family, and pyrin domain‐containing 3/caspase‐1 pathway mediated by the P2X7 receptor in the spinal trigeminal subnucleus caudalis.