Occupational exposure to toxic chemicals increases the risk of developing localized provoked vulvodynia - a prevalent, yet poorly understood, chronic condition characterized by sensitivity to touch and pressure, and accumulation of mast cells in painful tissues. Here, we topically sensitized female ND4 Swiss mice to the common household and industrial preservative methylisothiazolinone (MI) and subsequently challenged them daily with MI or acetone and olive oil vehicle on the labiar skin. MI-challenged mice developed significant, persistent tactile sensitivity and long-lasting local accumulation of mast cells alongside early, transient increases in CD4+ and CD8+ T cells, eosinophils, neutrophils, and increases in pro-inflammatory cytokines. Therapeutic administration of imatinib, a c-Kit inhibitor known to inhibit mast cell survival, led to reduced mast cell accumulation and alleviated tactile genital pain. We provide the first pre-clinical evidence of dermal MI-induced mast-cell dependent pain and lay the groundwork for detailed understanding of these intersections between MIdriven immunomodulation and chronic pain.
Bibliographical noteFunding Information:
This work was funded by National Institutes of Health 1R15AI113620-01A1 to D.C (https://www.nih.gov). JK, EAG, TY and SS were supported by summer stipends from an education grant from the Howard Hughes Medical Institute Foundation to Macalester College (https://www. hhmi.org). BB was supported by a Beckman Scholar Award to Macalester College from the Arnold and Mabel Beckman Foundation (https:// www.beckman-foundation.org). JK, EAG, TY, BB, JL, MS-M, NN, HM, SS, HZ, DP were additionally supported by intramural summer research awards from Macalester College. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.