Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia.
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.
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Jasmine
J
Landry
Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Tijana
T
Martinov
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Hanna
H
Mengistu
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Jyothi
J
Dhanwada
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Charles J
CJ
Benck
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Jaclyn
J
Kline
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Beebie
B
Boo
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Linnea
L
Swanson
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Elena
E
Tonc
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Randy
R
Daughters
Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Brian T
BT
Fife
Biology Department, Macalester College, St. Paul, Minnesota, United States of America.
Devavani
D
Chatterjea
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006241:Haptens / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010081:Oxazolone / Q000494:pharmacology*; D056650:Vulvodynia / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006241:Haptens; D053645:Interleukin-2 Receptor alpha Subunit; D010081:Oxazolone