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

Jasmine Landry, Tijana Martinov, Hanna Mengistu, Jyothi Dhanwada, Charles J. Benck, Jaclyn Kline, Beebie Boo, Linnea Swanson, Elena Tonc, Randy Daughters, Brian T. Fife, Devavani Chatterjea

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article numbere0169672
JournalPloS one
Volume12
Issue number2
DOIs
StatePublished - Feb 2017

Bibliographical note

Funding Information:
Support includes National Institutes of Health grants NIH R15 NS067536-01A1 and NIH R15 AI113620-01A1 (awarded to DC; https://www.nih.gov), a National Vulvodynia Association research grant (awarded to DC; http:// www.nva.org), and internal awards from Macalester College. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. CJB and JD received stipends from intra-mural programs supported by science education grants to Macalester College from the Arnold and Mabel Beckman Foundation (CJB) and the Howard Hughes Medical Research Institute (HM, JD). TM and BTF are supported by National Institute of Health grant R01AI106791.

Publisher Copyright:
© 2017 Landry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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