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In this study, we established a new animal model of trigeminal neuralgia and investigated the role of P2X<jats:sub>3<\/jats:sub> receptor (P2X<jats:sub>3<\/jats:sub>R) alteration in the trigeminal ganglion (TG) via tumor necrosis factor alpha (TNF\u03b1) signaling in persistent orofacial pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Trigeminal nerve root compression (TNC) was performed in male Sprague-Dawley rats. Changes in the mechanical sensitivity of whisker pad skin, amount of TNF\u03b1 in the TG, and number of P2X<jats:sub>3<\/jats:sub>R and TNF receptor-2 (TNFR2)-positive TG neurons were assessed following TNC. The effects of TNFR2 antagonism in TG and subcutaneous P2X<jats:sub>3<\/jats:sub>R antagonism on mechanical hypersensitivity following TNC were examined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TNC induced unilateral continuous orofacial mechanical allodynia, which was depressed by carbamazepine. The accumulation of macrophages showing amoeboid-like morphological changes and expression of TNF\u03b1 in the TG was remarkably increased following TNC treatment. The number of P2X<jats:sub>3<\/jats:sub>R-\u00a0and TNFR2-positive TG neurons innervating the orofacial skin was significantly increased following TNC. TNF\u03b1 was released from activated macrophages that occurred in the TG following TNC, and TNFR2 antagonism in the TG significantly diminished the TNC-induced increase in P2X<jats:sub>3<\/jats:sub>R-immunoreactive TG neurons. Moreover, subcutaneous P2X<jats:sub>3<\/jats:sub>R antagonism in the whisker pad skin significantly depressed TNC-induced mechanical allodynia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Therefore, it can be concluded that the signaling of TNF\u03b1 released from activated macrophages in the TG induces the upregulation of P2X<jats:sub>3<\/jats:sub>R expression in TG neurons innervating the orofacial region, resulting in orofacial mechanical allodynia following TNC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-021-01244-4","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T13:04:18Z","timestamp":1619442258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["P2X3 receptor upregulation in trigeminal ganglion neurons through TNF\u03b1 production in macrophages contributes to trigeminal neuropathic pain in rats"],"prefix":"10.1186","volume":"22","author":[{"given":"Momoko","family":"Koizumi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzuro","family":"Hitomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Shibuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiko","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusao","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Shinoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"1244_CR1","doi-asserted-by":"crossref","unstructured":"Kaji K, Shinoda M, Honda K, Unno S, Shimizu N, Iwata K (2016) Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury. 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