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

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5361
JournalInternational journal of molecular sciences
Volume20
Issue number21
DOIs
StatePublished - Nov 1 2019

Bibliographical note

Funding Information:
Funding: These studies were supported by NIH 1R15AI113620-01A1 to D.C., the Biology Department at Macalester College, and intramural undergraduate summer research stipends from Macalester College.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Allergy
  • Mast cells
  • Methylisothiazolinone
  • Vulvar pain
  • ∆-9 tetrahydrocannabinol

PubMed: MeSH publication types

  • Journal Article

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