{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:12:21Z","timestamp":1778580741295,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A5A2015391"],"award-info":[{"award-number":["2017R1A5A2015391"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1D1A1B07049025"],"award-info":[{"award-number":["2018R1D1A1B07049025"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Receptor-interacting serine\/threonine-protein kinase 1 (RIPK1) participates in the regulation of cellular stress and inflammatory responses, but its function in neuropathic pain remains poorly understood. This study evaluated the role of RIPK1 in neuropathic pain following inferior alveolar nerve injury. We developed a model using malpositioned dental implants in male Sprague Dawley rats. This model resulted in significant mechanical allodynia and upregulated RIPK1 expression in the trigeminal subnucleus caudalis (TSC). The intracisternal administration of Necrosatin-1 (Nec-1), an RIPK1 inhibitor, blocked the mechanical allodynia produced by inferior alveolar nerve injury The intracisternal administration of recombinant rat tumor necrosis factor-\u03b1 (rrTNF-\u03b1) protein in naive rats produced mechanical allodynia and upregulated RIPK1 expression in the TSC. Moreover, an intracisternal pretreatment with Nec-1 inhibited the mechanical allodynia produced by rrTNF-\u03b1 protein. Nerve injury caused elevated TNF-\u03b1 concentration in the TSC and a TNF-\u03b1 block had anti-allodynic effects, thereby attenuating RIPK1 expression in the TSC. Finally, double immunofluorescence analyses revealed the colocalization of TNF receptor and RIPK1 with astrocytes. Hence, we have identified that astroglial RIPK1, activated by the TNF-\u03b1 pathway, is a central driver of neuropathic pain and that the TNF-\u03b1-mediated RIPK1 pathway is a potential therapeutic target for reducing neuropathic pain following nerve injury.<\/jats:p>","DOI":"10.3390\/ijms23010506","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["TNF-\u03b1-Mediated RIPK1 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Jo Young","family":"Son","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Sook","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-2371","authenticated-orcid":false,"given":"Dong Kuk","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.cdd.4402085","article-title":"RIP1, a kinase on the crossroads of a cell\u2019s decision to live or die","volume":"14","author":"Festjens","year":"2007","journal-title":"Cell. 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