Mast cells are required for allergy-driven changes in senstivity to touch and pressure in oxazolone challenged skin in sensitized ND4 female mice.

Abstract

Vulvodynia is a chronic vulvar pain condition affecting up to 8–16% of 18–60 year-old women. Epidemiological studies have demonstrated an increased risk of developing vulvodynia for women with histories of seasonal and insect allergies. We show that 10 exposures to the hapten oxazolone on the labiar skin of previously sensitized outbred ND4 female mice provokes increased sensitivity to touch and pressure that lasts for 3 weeks or longer. This persistent sensitivity is accompanied by local labiar mast cell accumulation and overgrowth of cutaneous neurites both of which persist for at least 3 weeks after the final allergen exposure. Oxazolone-challenged mice also show local labiar increases in inflammatory cytokine and neuro-immune signaling transcripts, infiltration of resident memory CD8 cells and CD4+CD25+ regulatory T cells. Local depletion of mast cells via intra-dermal injections of basic secretagogue compound 48/80 reduces the sensitivity to touch and pressure suggesting that persistent accumulation of mast cells in allergen-exposed tissue is necessary for the development of long-lasting painful responses in these mice. Our findings suggest that mast cell-targeted therapies may be a novel area of intervention for the management and treatment of chronic pain conditions associated with allergic and hyper-inflammatory states.