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Earlier, we described the genetic association, within the Nuoro population, between Multiple Sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>) and rs28936, located in <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2 3\u2032<jats:styled-content style=\"fixed-case\">UTR<\/jats:styled-content>. Here we investigated the potential involvement of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2 in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> inflammatory process. We induced experimental autoimmune encephalomyelitis (<jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content>) in wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>), knockout Asic1<jats:sup>\u2212\/\u2212<\/jats:sup> and Asic2<jats:sup>\u2212\/\u2212<\/jats:sup> mice and observed a significant reduction of clinical score in Asic1<jats:sup>\u2212\/\u2212<\/jats:sup> mice and a significant reduction in the clinical score in Asic2<jats:sup>\u2212\/\u2212<\/jats:sup> mice in a limited time window (i.e., at days 20\u201323 after immunization). Immunohistochemistry confirmed the reduction in adaptive immune cell infiltrates in the spinal cord of <jats:styled-content style=\"fixed-case\">EAE<\/jats:styled-content> Asic1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2<jats:sup>\u2212\/\u2212<\/jats:sup> mice under physiological conditions, before immunization, as compared to <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice and Asic1<jats:sup>\u2212\/\u2212<\/jats:sup>. A significant reduction in pain threshold was observed in all three strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> and control samples showed an increase of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> samples. Subsequently, <jats:italic>in vitro<\/jats:italic> luciferase reporter gene assays, showed that <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2 expression is under possible mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> regulation, in a rs28936 allele\u2010specific manner. Taken together, these findings suggest a potential role of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>2 in the pathophysiology of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/ejn.14302","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T12:43:17Z","timestamp":1544791397000},"page":"1233-1243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Acid sensing ion channel 2: A new potential player in the pathophysiology of multiple sclerosis"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-8450","authenticated-orcid":false,"given":"Teresa","family":"Fazia","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Notartomaso","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. 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