Repeated vaginal exposures to the common cosmetic and household preservative methylisothiazolinone induce persistent, mast cell-dependent genital pain in ND4 mice

Erica Arriaga-Gomez, Macalester College
Jaclyn Kline, Macalester College
Elizabeth Emanuel, Macalester College
Nefeli Neamonitaki, Macalester College
Tenzin Yangdon, Macalester College
Hayley Zacheis, Macalester College
Dogukan Pasha, Macalester College
Jinyoung Lim, Macalester College
Susan Bush, Trinity College Hartford
Beebie Boo, Macalester College
Hanna Mengistu, Macalester College
Ruby Kinnamon, Macalester College
Robin Shields-Cutler, Macalester College
Elizabeth Wattenberg, School of Public Health
Devavani Chatterjea, Macalester College


© 2019 by the authors. Licensee MDPI, Basel, Switzerland. A history of allergies doubles the risk of vulvodynia—a 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)—a biocide preservative ubiquitous in cosmetics and cleaners—dissolved 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 ∆9-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.