{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:02:02Z","timestamp":1781848922262,"version":"3.54.5"},"reference-count":66,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Nihon University Research Grant"},{"name":"Sato Funds and the Dental Research Center of Nihon University School of Dentistry","award":["DRC(B)-2023-11"],"award-info":[{"award-number":["DRC(B)-2023-11"]}]},{"name":"JSPS KAKENHI","award":["20K10192 to A.O. and 21K10123 to I.S."],"award-info":[{"award-number":["20K10192 to A.O. and 21K10123 to I.S."]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>Background: Trigeminal nerve injury causes orofacial pain that can interfere with activities of daily life. However, the underlying mechanism remains unknown, and the appropriate treatment has not been established yet. This study aimed to examine the involvement of interferon gamma (IFN-\u03b3) signaling in the spinal trigeminal caudal subnucleus (Vc) in orofacial neuropathic pain. Methods: Infraorbital nerve (ION) injury (IONI) was performed in rats by partial ION ligation. The head-withdrawal reflex threshold (HWT) to mechanical stimulation of the whisker pad skin was measured in IONI or sham rats, as well as following a continuous intracisterna magna administration of IFN-\u03b3 and a mixture of IFN-\u03b3 and fluorocitrate (inhibitor of astrocytes activation) in na\u00efve rats, or an IFN-\u03b3 antagonist in IONI rats. The IFN-\u03b3 receptor immunohistochemistry and IFN-\u03b3 Western blotting were analyzed in the Vc after IONI or sham treatment. The glial fibrillary acid protein (GFAP) immunohistochemistry and Western blotting were also analyzed after administration of IFN-\u03b3 and the mixture of IFN-\u03b3 and fluorocitrate. Moreover, the change in single neuronal activity in the Vc was examined in the IONI, sham, and IONI group administered IFN-\u03b3 antagonist. Results: The HWT decreased after IONI. The IFN-\u03b3 and IFN-\u03b3 receptor were upregulated after IONI, and the IFN-\u03b3 receptor was expressed in Vc astrocytes. IFN-\u03b3 administration decreased the HWT, whereas the mixture of IFN-\u03b3 and fluorocitrate recovered the decrement of HWT. IFN-\u03b3 administration upregulated GFAP expression, while the mixture of IFN-\u03b3 and fluorocitrate recovered the upregulation of GFAP expression. IONI significantly enhanced the neuronal activity of the mechanical-evoked responses, and administration of an IFN-\u03b3 antagonist significantly inhibited these enhancements. Conclusions: IFN-\u03b3 signaling through the receptor in astrocytes is a key mechanism underlying orofacial neuropathic pain associated with trigeminal nerve injury. These findings will aid in the development of therapeutics for orofacial neuropathic pain.<\/jats:p>","DOI":"10.1177\/17448069231222403","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T01:52:55Z","timestamp":1702259575000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Involvement of interferon gamma signaling in spinal trigeminal caudal subnucleus astrocyte in orofacial neuropathic pain in rats with infraorbital nerve injury"],"prefix":"10.1177","volume":"19","author":[{"given":"Sayaka","family":"Asano","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan"},{"name":"Department of Physiology, Nihon University School of Dentistry, Tokyo, 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