{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:25:07Z","timestamp":1791761107458,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DE031255"],"award-info":[{"award-number":["R01DE031255"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DE032061"],"award-info":[{"award-number":["R01DE032061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R03DE031822"],"award-info":[{"award-number":["R03DE031822"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Previous studies have demonstrated an association between migraine headache and temporomandibular joint disorders (TMDs), with a higher prevalence of TMD symptoms in patients with migraine. Methods: In this study, we conducted RNA sequencing to identify differentially expressed genes (DEGs) in the spinal trigeminal nucleus caudalis of mice with migraine-like pain and\/or myogenic TMD. Results: We observed 204 upregulated and 274 downregulated genes in the comorbid migraine and TMD group compared to the control group. We identified 15 ferroptosis-related DEGs enriched in the pathways of neurodegeneration, cellular homeostasis, interleukin signaling, and pain response. Gene Ontology analysis highlighted the involvement of neuroinflammatory response and monoamine transmembrane transporter activity, while Gene Set Enrichment analysis showed enrichment in chemokine signaling, cell cycle, and calcium signaling pathways. Immune infiltration analysis identified M0 macrophages, immature dendritic cells, neutrophils, and eosinophils as key responders. Hub genes in the protein\u2013protein interaction network included Gm7536, Rpl17, Rpl22l1, Rpl14, Rps8, Rps29, Rpl35, Gm4889, Gm11808, Rps27rt, Rps12-ps3, Rpl10-ps3, Gm9843, Oas1c, Il1b, and Serpine1, indicating their synergistic roles in such orofacial pain comorbidity. Conclusions: Our results suggest that the comorbid migraine and TMD can regulate gene expressions involving ferroptosis and immune cell responses and the identified DEGs could be targeted to develop novel therapies for this painful comorbidity.<\/jats:p>","DOI":"10.3390\/genes16121435","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Gene Regulation in Comorbid Migraine and Myogenic Temporomandibular Disorder Pain"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-3992","authenticated-orcid":false,"given":"Ran","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Maltezos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-6298","authenticated-orcid":false,"given":"Feng","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1093\/brain\/awaa242","article-title":"Functional gene networks reveal distinct mechanisms segregating in migraine families","volume":"143","author":"Rasmussen","year":"2020","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41368-022-00185-1","article-title":"Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice","volume":"14","author":"Lai","year":"2022","journal-title":"Int. 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