{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:03:38Z","timestamp":1783739018306,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["3R15AI113620-01A1S1"],"award-info":[{"award-number":["3R15AI113620-01A1S1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R15AI113620-01A1"],"award-info":[{"award-number":["1R15AI113620-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A history of allergies doubles the risk of vulvodynia\u2014a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)\u2014a biocide preservative ubiquitous in cosmetics and cleaners\u2014dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of \u03949-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.<\/jats:p>","DOI":"10.3390\/ijms20215361","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T11:26:13Z","timestamp":1572261973000},"page":"5361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-6751","authenticated-orcid":false,"given":"Erica","family":"Arriaga-Gomez","sequence":"first","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Kline","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Emanuel","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nefeli","family":"Neamonitaki","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenzin","family":"Yangdon","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Zacheis","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dogukan","family":"Pasha","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyoung","family":"Lim","sequence":"additional","affiliation":[{"name":"Mathematics, Statistics &amp; Computer Science Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1638-4515","authenticated-orcid":false,"given":"Susan","family":"Bush","sequence":"additional","affiliation":[{"name":"Biology Department, Trinity College, Hartford, CT 06106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beebie","family":"Boo","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mengistu","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Kinnamon","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Shields-Cutler","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wattenberg","sequence":"additional","affiliation":[{"name":"Division of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devavani","family":"Chatterjea","sequence":"additional","affiliation":[{"name":"Biology Department, Macalester College, Saint Paul, MN 55105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ajog.2011.08.012","article-title":"Prevalence and demographic characteristics of vulvodynia in a population-based sample","volume":"206","author":"Reed","year":"2012","journal-title":"Am. 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