{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:00:14Z","timestamp":1791856814543,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006732","name":"New York University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006636","name":"University of Maryland, Baltimore County","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Temporomandibular disorders (TMD) and migraine can be co\u2010morbid. This can be a significant factor in exacerbating and increasing the prevalence of migraine\u2010like symptoms. However, the underlying mechanisms involved are unknown. Our objective was to investigate these neural mechanisms and the role of CGRP as a key modulator in this co\u2010morbidity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We combined experimental approaches using CGRP, which triggers a migraine\u2010like response in patients, with that of masseteric muscle injection of complete Freund's adjuvant (CFA), to model myofascial TMD\u2010like inflammation. Using validated electrophysiological methods to assess each of the above approaches independently or in combination, we examined their effects on the response properties of migraine\u2010like dural\u2010trigeminocervical neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Independently, in ~2\/3 of animals (rats) each approach caused delayed migraine\u2010like activation and sensitisation of dural\u2010trigeminocervical neurons. The response to masseteric\u2010CFA was attenuated by a selective CGRP receptor antagonist. The combination approach caused a migraine\u2010like neuronal response in all animals tested, with somatosensory\u2010evoked cranial hypersensitivity significantly exacerbated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The data demonstrate a neuronal phenotype that translates to the exacerbated clinical co\u2010morbid phenotype, supporting this combination approach as a relevant model to study the mechanisms involved. It provides a pathophysiological rationale for this exacerbated phenotype, strongly implicating the involvement of CGRP. The results provide support for targeting the CGRP pathway as a novel monotherapy approach for treating this co\u2010morbid condition. This has key implications into our understanding of this co\u2010morbid condition, as well as potentially addressing the major unmet need for novel and effective therapeutic approaches.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15263","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T08:00:54Z","timestamp":1600761654000},"page":"5555-5568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Preclinical studies investigating the neural mechanisms involved in the co\u2010morbidity of migraine and temporomandibular disorders: the role of CGRP"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6577-6825","authenticated-orcid":false,"given":"Simon","family":"Akerman","sequence":"first","affiliation":[{"name":"Department of Neural and Pain Sciences University of Maryland Baltimore  Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-0527","authenticated-orcid":false,"given":"Marcela","family":"Romero\u2010Reyes","sequence":"additional","affiliation":[{"name":"Department of Neural and Pain Sciences University of Maryland Baltimore  Baltimore MD 21201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa7557"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.06.028"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws249"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy313"},{"key":"e_1_2_11_6_1","first-page":"271678X17729280","article-title":"Targeting the central projection of the dural trigeminovascular system for migraine prophylaxis","author":"Akerman S.","year":"2017","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"1","key":"e_1_2_11_7_1","first-page":"S21","article-title":"The concise guide to pharmacology 2019\/20: G protein\u2010coupled receptors","volume":"176","author":"Alexander S. 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