TRPV1 mediates itch-associated scratching and skin barrier dysfunction in DNFB-induced atopic dermatitis mice.

Abstract

In chronic pruritic diseases such as atopic dermatitis (AD), pruritus and skin lesions are exacerbated by scratching in clinical and experimental settings. TRPV1 is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in itch-associated scratching in AD is poorly understood. In this study, we examined the efficacy of cutting off nailsand TRPV1 antagonist, ruthenium red (RR) in a murine model of AD induced by DNFB and further investigated the underlying mechanism. Nail clipping or RR could markedly ameliorate the general AD-like symptoms as manifested by the reduced clinical severity of dermatitis, IgE and Th2-related cytokine levels, and mast cell degranulation. Moreover, scratching behaviour, the levels of pruritogenic mediators, including HIS, TSLP, IL-31 and SP, and skin pH and TEWL were all significantly decreased in nail clipping or RR-treated mice, suggesting a reduction in itch-associated scratching and skin barrier defects. Immunofluorescence staining and Western blot results revealed thatantipruriticeffect ofnail clipping or RR in AD may be explained, at least in part, by the suppression of TRPV1 activation. In summary, these data show that TRPV1mediates itch-associated scratching and subsequent skin barrier defects, suggesting its potential as a therapeutic target in AD.