Repeated allergen challenge provokes mechanical sensitivity, hyper-innervation and mast cell accumulation in the vulvar tissue of mice

Epidemiological evidence suggests a link between a history of environmental allergies and the risk of developing vulvodynia - a chronic provoked vulvar pain condition affecting up to 20% of women in populates assessed. We have previously shown that acute labiar exposure to a hapten allergen provokes increased mechanical sensitivity in the vulvar tissue of sensitized mice. Here, we show repeated challenge with contact hypersensitivity allergen oxazolone produces sustained mechanical hyperalgesia in the vulvar region of previously sensitized female mice for 10-14 days after final allergen exposure. Acute inflammatory responses including labiar neutrophil influx, T and B cell amplification in the draining iliac lymph nodes, labiar expression of inflammatory cytokine genes (IL-6, IL-1β and Cxcl-2) are all resolved within 5 days after final allergen exposure while increased densities of both peptidergic nerve fibers and mast cells in the labiar tissue are observed. Our findings provide the first evidence of the induction of measurable and sustained pain persisting after the resolution of overt inflammatory events following an allergic response in the labiar/vulvar tissue in mice. We have established the first model of chronic allergy-provoked vulvar pain in mice that can be used to elucidate the underlying etiology of subsets of vulvar pain that present without accompanying inflammation and are associated with histories of allergic skin responses.