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The GluN1 subunit undergoes alternative splicing at exon 5, generating isoforms GluN1a (lacking the exon 5\u2010encoded N1 cassette) and GluN1b (retaining the N1 cassette), which have distinct functional roles. However, the contribution of GluN1 exon 5 splicing and the mechanisms governing this process in orofacial neuropathic pain are not fully understood. This study investigates the role of GluN1 exon 5 splicing in the development of orofacial allodynia utilizing a mouse model of chronic constriction injury of the infraorbital nerve (CCI\u2010ION). We found that CCI\u2010ION induces enhanced exon 5 splicing in the trigeminal ganglion (TG), promoting the expression of GluN1a and contributing to orofacial allodynia. A key regulator of this splicing event is the polypyrimidine tract\u2010binding protein (PTB), which binds to GluN1 pre\u2010mRNA in a manner dependent on PTB dimerization. We also identified protein disulfide isomerase 3 (PDIA3) as a modulator of PTB dimerization. PDIA3 regulates the formation of PTB dimers in the nucleus, which drives GluN1 exon 5 splicing and the development of orofacial allodynia. These findings reveal a PDIA3\u2010PTB\u2010GluN1 axis that regulates alternative splicing of GluN1 exon 5 in response to trigeminal nerve injury, providing new insights into the molecular mechanisms underlying orofacial neuropathic pain and potential therapeutic targets for its treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70220-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70220","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:47:11Z","timestamp":1757065631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternative Splicing of the\n                    <scp>NMDA<\/scp>\n                    Receptor Subunit\n                    <scp>GluN1<\/scp>\n                    Mediated by Polypyrimidine Tract\u2010Binding Protein Dimerization in the Trigeminal Ganglion Contributes to Orofacial Allodynia"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0812-1253","authenticated-orcid":false,"given":"Yi\u2010Ke","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu 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West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin\u2010Xuan","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu China"},{"name":"Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Center of Anesthesiology, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key 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