Investigation of the participation of the TRPV1 receptor in the irritant effect of dithranol in mice

Abstract

Dithranol is one of the most effective topical medications for treating plaque psoriasis. However, its clinical use is
limited by irritative adverse reactions to the skin, such as oedema, erythema, and pruritus, caused by poorly
understood mechanisms. Because TRPV1 activation mediates skin irritation caused by several drugs, we conducted
blind and randomised experiments in male and female C57BL/6 mice to elucidate the role of TRPV1 in
dithranol-induced irritation. Dithranol (0.01%–0.5%) or vehicle was applied topically to the right ear of the
animals. Oedema, erythema, and pruritus were monitored from 2 h to 6 days after application. Treatment with
0.5% dithranol caused oedema and erythema, but not pruritus, starting at 6 h, reaching its highest point at 1 day,
and persisting up to 6 days after treatment, mainly in male mice. The 0.1% dose induced erythema but not
oedema. Interestingly, topical application of 1% capsaicin was shown to defunctionalise TRPV1-positive fibres
and did not influence early irritation caused by dithranol (2 h–2 days). However, it increased the late phase of
irritation (5–6 days). Similarly, salicylate did not reduce the early irritation caused by dithranol but also
increased the late phase. Antagonism by SB366791 and 4-tert-butylcyclohexanol did not alter skin irritation. Our
results suggest that, contrary to our initial hypothesis, TRPV1 appears to act protectively against skin irritation
caused by dithranol, particularly in the late stage.

keywords

Neurogenic inflammation
Anthralin
TRP channels
Psoriasis

authors

Ana Merian da Silva, Marcella de Amorim Ferreira,Roberta Giusti Schran,
Debora Denardin Lückemeyer, Arthur Silveira Prudente, Juliano Ferreira