{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:36:38Z","timestamp":1790717798605,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>P2Y<jats:sub>12<\/jats:sub> receptors regulate different forms of pain and inflammation. In this study, we investigated the participation of P2Y<jats:sub>12<\/jats:sub> receptors in an animal model of migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We tested the effect of the centrally administered selective P2Y<jats:sub>12<\/jats:sub> antagonist PSB\u20100739 and P2Y<jats:sub>12<\/jats:sub> receptor gene (<jats:italic>P2ry12<\/jats:italic><jats:sup>\u2010\/\u2010<\/jats:sup>) deficiency in acute nitroglycerin\u2010treated mice. Additionally, platelet depletion was used to investigate the role of platelet P2Y<jats:sub>12<\/jats:sub> receptors during migraine\u2010like pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Nitroglycerin induced sensory hypersensitivity of C57BL\/6 wild\u2010type (<jats:italic>P2ry12<\/jats:italic><jats:sup>+\/+<\/jats:sup>) mice accompanied by an increase in c\u2010fos and CGRP expression in the upper cervical spinal cord (C1\u2013C2) and trigeminal nucleus caudalis. Similar changes were also observed in P2Y<jats:sub>12<\/jats:sub> gene\u2010deficient (<jats:italic>P2ry12<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Prophylactic intrathecal application of PSB\u20100739 reversed thermal hyperalgesia and head grooming time in wild\u2010type mice but had no effect in <jats:italic>P2ry12<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Furthermore, PSB\u20100739 was also effective when applied as a post\u2010treatment. PSB\u20100739 administration suppressed the expression of c\u2010fos in C1\u2013C2 and trigeminal nucleus caudalis, and decreased the levels of dopamine and 5\u2010hydroxytryptamine in C1\u2010C2 in wild\u2010type mice. Nitroglycerin treatment itself did not change adenosine diphosphate (ADP)\u2010induced platelet activation measured by CD62P up\u2010regulation in wild\u2010type mice. Platelet depletion by anti\u2010mouse CD41 antibody and clopidogrel attenuated nitroglycerin\u2010induced thermal hypersensitivity and head grooming time in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings show that acute inhibition of P2Y<jats:sub>12<\/jats:sub> receptors alleviates migraine\u2010like pain in mice by modulating the expression of c\u2010fos and that platelet P2Y<jats:sub>12<\/jats:sub> receptors might contribute to this effect. Thus the blockade of P2Y<jats:sub>12<\/jats:sub> receptors may have therapeutic potential against migraine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15641","type":"journal-article","created":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T03:21:30Z","timestamp":1628306490000},"page":"4626-4645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Involvement of P2Y<sub>12<\/sub> receptors in a nitroglycerin\u2010induced model of migraine in male mice"],"prefix":"10.1111","volume":"178","author":[{"given":"Fl\u00f3ra","family":"G\u00f6l\u00f6ncs\u00e9r","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology Institute of Experimental Medicine  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"Baranyi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology Institute of Experimental Medicine  Budapest 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