{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:29:53Z","timestamp":1776439793454,"version":"3.51.2"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"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":"publisher","award":["R01 DE022880 and K02 DE023551"],"award-info":[{"award-number":["R01 DE022880 and K02 DE023551"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Migraine is commonly reported among patients with temporomandibular disorders (TMDs), especially myogenic TMD. The pathophysiologic mechanisms related to the comorbidity of the two conditions remain elusive. In the present study, we combined masseter muscle tendon ligation (MMTL)-produced myogenic TMD with systemic injection of nitroglycerin (NTG)-induced migraine-like hypersensitivity in mice. Facial mechanical allodynia, functional allodynia, and light-aversive behavior were evaluated. Sumatriptan, an FDA-approved medication for migraine, was used to validate migraine-like hypersensitivity. Additionally, we examined the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis using immunohistochemistry. We observed that mice with MMTL pretreatment have a prolonged NTG-induced migraine-like hypersensitivity, and MMTL also enabled a non-sensitizing dose of NTG to trigger migraine-like hypersensitivity. Systemic injection of sumatriptan inhibited the MMTL-enhanced migraine-like hypersensitivity. MMTL pretreatment significantly upregulated the protein level of CGRP in the spinal trigeminal nucleus caudalis after NTG injection. Our results indicate that a pre-existing myogenic TMD can upregulate NTG-induced trigeminal CGRP and enhance migraine-like hypersensitivity.<\/jats:p>","DOI":"10.3390\/ijms21114049","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T05:16:14Z","timestamp":1591679774000},"page":"4049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A Pre-Existing Myogenic Temporomandibular Disorder Increases Trigeminal Calcitonin Gene-Related Peptide and Enhances Nitroglycerin-Induced Hypersensitivity in Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Hui","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sufang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"},{"name":"Department of Physiology and Neurobiology, Zhengzhou University School of Medicine, Zhengzhou 450001, Henan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"},{"name":"School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Bluestone Center for Clinical Research, New York University, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Dolan","sequence":"additional","affiliation":[{"name":"Bluestone Center for Clinical Research, New York University, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry L.","family":"Bellinger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip R.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven D.","family":"Bender","sequence":"additional","affiliation":[{"name":"Center for Facial Pain and Sleep Medicine, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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&amp;M University College of Dentistry, Dallas, TX 75246, USA"},{"name":"Center for Craniofacial Research and Diagnosis, Texas A&amp;M University College of Dentistry, Dallas, TX 75246, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/head.12482","article-title":"The prevalence and burden of migraine and severe headache in the United States: Updated statistics from government health surveillance studies","volume":"55","author":"Burch","year":"2015","journal-title":"Headache"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.11607\/jop.1151","article-title":"Diagnostic Criteria for Temporomandibular Disorders (DC\/TMD) for Clinical and Research Applications: Recommendations of the International RDC\/TMD Consortium Network* and Orofacial Pain Special Interest Groupdagger","volume":"28","author":"Schiffman","year":"2014","journal-title":"J. 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