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Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia

1
Biology Department, Macalester College, Saint Paul, MN 55105, USA
2
Center for Immunology, University of Minnesota, Minnesota, MN 55455, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2163; https://doi.org/10.3390/ijms20092163
Received: 28 March 2019 / Revised: 23 April 2019 / Accepted: 26 April 2019 / Published: 1 May 2019
(This article belongs to the Special Issue Mast Cells in Health and Disease)
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Abstract

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures. View Full-Text
Keywords: mast cells; dinitrofluorobenzene; hypersensitivity; chronic pain; vulvodynia; Δ9-tetrahydrocannabinol mast cells; dinitrofluorobenzene; hypersensitivity; chronic pain; vulvodynia; Δ9-tetrahydrocannabinol
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Boo, B.; Kamath, R.; Arriaga-Gomez, E.; Landry, J.; Emanuel, E.; Joo, S.; Saldías Montivero, M.; Martinov, T.; Fife, B.T.; Chatterjea, D. Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia. Int. J. Mol. Sci. 2019, 20, 2163.

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