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However, the neuronal mechanisms underlying TN pathogenesis remain largely unknown. Here, we identify a periphery\u2010to\u2010brain neural circuit that governs TN development in mice. Tachykinin 1 (\n                    <jats:italic>Tac1<\/jats:italic>\n                    )\u2010expressing parabrachial nucleus (PBN\n                    <jats:sup>Tac1<\/jats:sup>\n                    ) neurons show heightened stimulus\u2010evoked responses, and chemogenetic inhibition of these neurons effectively prevents TN development. Furthermore, PBN\n                    <jats:sup>Tac1<\/jats:sup>\n                    neurons receive projections from the caudal part of the spinal trigeminal nucleus (Sp5C), and PBN\u2010projecting Sp5C neurons are essential for TN\u2010induced pain hypersensitivity. Remarkably, PBN\u2010projecting Sp5C neurons predominantly express\n                    <jats:italic>Tac1<\/jats:italic>\n                    , and knockdown\n                    <jats:italic>Tac1<\/jats:italic>\n                    gene in these neurons significantly attenuates TN\u2010induced pain hypersensitivity. Through retrograde viral tracing and electrophysiological recordings, we demonstrate that\n                    <jats:italic>Tac1<\/jats:italic>\n                    \u2010expressing Sp5C neurons directly relay signals from the trigeminal ganglion (TG) to the PBN. Collectively, our findings unveil a critical TG\u2010Sp5C\n                    <jats:sup>Tac1<\/jats:sup>\n                    \u2010PBN\n                    <jats:sup>Tac1<\/jats:sup>\n                    pathway that drives the TN pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516310","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:54:29Z","timestamp":1773428069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A\n                    <i>Tac1<\/i>\n                    \u2010Expressing Brainstem Pathway Underlies the Pathogenesis of Trigeminal Neuralgia"],"prefix":"10.1002","volume":"13","author":[{"given":"Liting","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Huadong Hospital State Key Laboratory of Medical Neurobiology Institute for Translational Brain Research MOE Frontiers Center for Brain Science Fudan 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