{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:24:24Z","timestamp":1777353864694,"version":"3.51.4"},"reference-count":94,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health to Institute C. Mondino (RC 2014\u20132016)"},{"name":"Universit\u00e0 degli Studi di Milano-Piano di Sostegno alla Ricerca 2017 Linea 2 (to SC)"},{"name":"Italian Ministry of Research and University (MUR) Finanziamento Annuale Individuale delle Attivit\u00e0 di Base di Ricerca 2017 (to SC)"},{"name":"MUR \u201cDepartment of Excellence\u201d grant program of the Department of Pharmacological and Biomolecular Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated\/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges. Rats were treated with ADM_12 (TRPA1 antagonist) and then underwent an orofacial formalin test to assess trigeminal hyperalgesia. mRNA levels of pro- and anti-inflammatory cytokines, calcitonin gene-related peptide (CGRP) and glia cell activation were evaluated in the Medulla oblongata and in the trigeminal ganglia. In the nitroglycerin-treated rats, ADM_12 showed an antihyperalgesic effect in both acute and chronic models, and it counteracted the changes in CGRP and cytokine gene expression. In the acute nitroglycerin model, ADM_12 reduced nitroglycerin-induced increase in microglial and astroglial activation in trigeminal nucleus caudalis area. In the chronic model, we detected a nitroglycerin-induced activation of satellite glial cells in the trigeminal ganglia that was inhibited by ADM_12. These findings show that TRPA1 antagonism reverts experimentally induced hyperalgesia in acute and chronic models of migraine and prevents multiple changes in inflammatory pathways by modulating glial activation.<\/jats:p>","DOI":"10.3390\/ijms232214085","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:24:53Z","timestamp":1668565493000},"page":"14085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-7773","authenticated-orcid":false,"given":"Chiara","family":"Demartini","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Via Bassi 21, 27100 Pavia, Italy"},{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Greco","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0995-8947","authenticated-orcid":false,"given":"Giulia","family":"Magni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Zanaboni","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Via Bassi 21, 27100 Pavia, Italy"},{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Riboldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Francavilla","sequence":"additional","affiliation":[{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Nativi","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cUgo Schiff\u201d, University of Florence, Via Della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-4211","authenticated-orcid":false,"given":"Stefania","family":"Ceruti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, Via Bassi 21, 27100 Pavia, Italy"},{"name":"Unit of Translational Neurovascular Research, IRCCS Mondino Foundation, Via Mondino 2, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","unstructured":"GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (2016). 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