{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:58:35Z","timestamp":1783857515775,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Migraine is a disease that stands out for its high prevalence and socioeconomic costs. It involves the entire trigeminovascular system, the signaling substances, and their targets. However, the role of meningeal mast cells in migraine is still unclear. To better understand one of the components of neurogenic inflammation underlying migraine pathophysiology, we developed an in vivo rat model in which the dura mater was exposed bilaterally to investigate the influence of topiramate on capsaicin-induced mast cell degranulation and CGRP release from dura mater. Methods: On the day of the experiment, rats were anesthetized, and a craniectomy was performed on each parietal bone. Test substances were applied in situ over the dura mater using the right and left sides of the dura mater for the test and control, respectively. After exposure, the dura mater was processed for mast cell staining and counting. Using this setup, the effect of capsaicin (10\u22123 M) was evaluated in rats of both sexes, and subsequently the effect of in situ (10\u22123 M, 20 \u00b5L) and (20 mg\/kg\/day for 10 days) topiramate treatment on mast cell degranulation and CGRP release were evaluated. Results: In both female and male rats, there was a greater amount of degranulated mast cells in the side stimulated by capsaicin compared to the control side in both females (18 \u00b1 3% vs. 74 \u00b1 3%; p = 0.016) and males (28 \u00b1 2% vs. 74 \u00b1 3%, p = 0.016). In the group treated with topiramate for 10 days prior to the experiments, capsaicin did not induce mast cell degranulation (control 20 \u00b1 1% vs. capsaicin 22 \u00b1 1%, p = 0.375) in contrast to animals treated for 10 days with gavage control (control 25 \u00b1 1% vs. capsaicin 76 \u00b1 1%, p = 0.016). Topiramate applied in situ concomitant with capsaicin did not protect the mast cells from degranulation in response to capsaicin (38 \u00b1 2% vs. 44 \u00b1 1%, p = 0.016). There was a significant reduction in CGRP release from the dura mater in the group treated with topiramate for 10 days compared to the control. Conclusions: This study demonstrates a novel experimental model wherein systemic administration of topiramate is observed to modulate the impact of capsaicin on meningeal mast cell degranulation.<\/jats:p>","DOI":"10.3390\/brainsci14111070","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Topiramate Inhibits Capsaicin-Induced Mast Cell Degranulation and CGRP Release in Rat Dura Mater"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-6689","authenticated-orcid":false,"given":"Raisa Ferreira","family":"Costa","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biology Science, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela Paz","family":"Rosas","sequence":"additional","affiliation":[{"name":"Immunopathology Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvania Tavares","family":"Paz","sequence":"additional","affiliation":[{"name":"Anatomy Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Figueiroa Lyra de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Patology Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Lopes de","family":"Souza","sequence":"additional","affiliation":[{"name":"Neuropsychiatry and Behavioral Sciences Laboratory, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-8872","authenticated-orcid":false,"given":"Juliana Ramos de","family":"Andrade","sequence":"additional","affiliation":[{"name":"Immunopathology Laboratory (LIKA), Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella Ara\u00fajo de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Physiotherapy Department, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4460-2586","authenticated-orcid":false,"given":"Inger","family":"Jansen-Olesen","sequence":"additional","affiliation":[{"name":"Neurology Department, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, 2600 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-4783","authenticated-orcid":false,"given":"Sarah Louise","family":"Christensen","sequence":"additional","affiliation":[{"name":"Neurology Department, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, 2600 Copenhagen, Denmark"},{"name":"Anesthesia Department, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0678-3782","authenticated-orcid":false,"given":"Marcelo Moraes","family":"Valen\u00e7a","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/archsurg.1940.01210040002001","article-title":"Experimental Studuies on Headache: Pain-Sensitive Structures of the Head and Their Significance in Headache","volume":"41","author":"Ray","year":"1940","journal-title":"Arch. 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