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Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.


ABSTRACT:

Background

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure.

Methods

We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later with oxazolone or vehicle for ten consecutive days on the labia. We evaluated labiar sensitivity to touch, local mast cell accumulation, and hyperinnervation after ten challenges.

Results

Oxazolone-challenged mice developed significant tactile sensitivity that persisted for over three weeks after labiar allergen exposures ceased. Allergic sites were characterized by mast cell accumulation, sensory hyper-innervation and infiltration of regulatory CD4+CD25+FoxP3+ T cells as well as localized early increases in transcripts encoding Nerve Growth Factor and nerve-mast cell synapse marker Cell Adhesion Molecule 1. Local depletion of mast cells by intra-labiar administration of secretagogue compound 48/80 led to a reduction in both nerve density and tactile sensitivity.

Conclusions

Mast cells regulate allergy-provoked persistent sensitivity to touch. Mast cell-targeted therapeutic strategies may provide novel means to manage and limit chronic pain conditions associated with atopic disease.

SUBMITTER: Landry J 

PROVIDER: S-EPMC5291437 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.

Landry Jasmine J   Martinov Tijana T   Mengistu Hanna H   Dhanwada Jyothi J   Benck Charles J CJ   Kline Jaclyn J   Boo Beebie B   Swanson Linnea L   Tonc Elena E   Daughters Randy R   Fife Brian T BT   Chatterjea Devavani D  

PloS one 20170203 2


<h4>Background</h4>Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure.<h4>Methods</h4>We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later wit  ...[more]

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