{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:47Z","timestamp":1790702027325,"version":"4.1.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["PhD and interuniversity exchange fellowships"],"award-info":[{"award-number":["PhD and interuniversity exchange fellowships"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH1R01NS106902"],"award-info":[{"award-number":["NIH1R01NS106902"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Determine the role of calcitonin-gene related peptide in promoting post-traumatic headache and dysregulation of central pain modulation induced by mild traumatic brain injury in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mild traumatic brain injury was induced in lightly anesthetized male C57BL\/6J mice by a weight drop onto a closed and unfixed skull, which allowed free head rotation after the impact. We first determined possible alterations in the diffuse noxious inhibitory controls, a measure of net descending pain inhibition called conditioned pain modulation in humans at day 2 following mild traumatic brain injury. Diffuse noxious inhibitory control was assessed as the latency to a thermally induced tail-flick that served as the test stimulus in the presence of right forepaw capsaicin injection that provided the conditioning stimulus. Post-traumatic headache-like behaviors were assessed by the development of cutaneous allodynia in the periorbital and hindpaw regions after mild traumatic brain injury. We then determined if intraperitoneal fremanezumab, an anti-calcitonin-gene related peptide monoclonal antibody or vehicle administered 2\u2009h after sham or mild traumatic brain injury induction could alter cutaneous allodynia or diffuse noxious inhibitory control responses on day 2 post mild traumatic brain injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In na\u00efve and sham mice, capsaicin injection into the forepaw elevated the latency to tail-flick, reflecting the antinociceptive diffuse noxious inhibitory control response. Periorbital and hindpaw cutaneous allodynia, as well as a loss of diffuse noxious inhibitory control, was observed in mice 2 days after mild traumatic brain injury. Systemic treatment with fremanezumab blocked mild traumatic brain injury-induced cutaneous allodynia and prevented the loss of diffuse noxious inhibitory controls in mice subjected to a mild traumatic brain injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Sequestration of calcitonin-gene related peptide in the initial stages following mild traumatic brain injury blocked the acute allodynia that may reflect mild traumatic brain injury-related post-traumatic headache and, additionally, prevented the loss of net descending inhibition within central pain modulation pathways. As loss of conditioned pain modulation has been linked to multiple persistent pain conditions, dysregulation of descending modulatory pathways may contribute to the persistence of post-traumatic headache. Additionally, evaluation of the conditioned pain modulation\/diffuse noxious inhibitory controls response may serve as a biomarker of vulnerability for chronic\/persistent pain. These findings suggest that early anti-calcitonin-gene related peptide intervention has the potential to be effective both for the treatment of mild traumatic brain injury-induced post-traumatic headache, as well as inhibiting mechanisms that may promote post-traumatic headache persistence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0333102420981688","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:34:34Z","timestamp":1613954074000},"page":"749-759","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["CGRP monoclonal antibody prevents the loss of diffuse noxious inhibitory controls (DNIC) in a mouse model of post-traumatic headache"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-5117","authenticated-orcid":false,"given":"Caroline M","family":"Kopruszinski","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle M","family":"Turnes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Federal University of Parana, Curitiba, Parana, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Swiokla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy J","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J","family":"Schwedt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Dodick","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trent","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, University of Arizona, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-125X","authenticated-orcid":false,"given":"Edita","family":"Navratilova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Porreca","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA"},{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"bibr1-0333102420981688","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0243-8"},{"key":"bibr2-0333102420981688","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-018-0720-6"},{"key":"bibr3-0333102420981688","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00615"},{"key":"bibr4-0333102420981688","first-page":"1","volume-title":"Cephalalgia","volume":"38","author":"Headache Classification Committee of the International Headache 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