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

Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, characterized by a T helper (Th)-2 cell-dominant inflammatory infiltrate and a defective epidermal permeability barrier. 1,2 Itch (or pruritus) is the major symptom of AD and causes a negative impact on quality of life. Intense itching is an unpleasant sensation, which evokes a strong desire to scratch. Moreover, itch-induced scratching aggravates skin lesions, and a vicious itch-scratch circle and consequent skin barrier destruction are easily established. 3,4 Previous studies exhibited that reducing physical stimulus to the skin, such as nail clipping, inhibits the development of AD in patients and AD-like phenotypes in a spontaneous mouse model. 5,6 However, the underlying mechanism through which scratching exacerbates dermatitis remains to be investigated.Transient receptor potential vanilloid type 1 (TRPV1), a nonselective cation channel with high permeability to calcium widely expressed in the epidermal keratinocytes, can be activated by heat, capsaicin, mechanical stimulus and endogenous inflammatory mediators. Stimulation of TRPV1 is reported to trigger neurogenic inflammatory mediator and neuropeptide releases, which ultimately contributes to the development of pruritus and diverse dermatoses. 7,8 Given the involvement of the TRPV1 receptor in the itching associated with pruritic inflammatory skin disease, we hypothesized

Transient Receptor Potential Channels and Itch

“…This adverse effect was thought to be due to TRPV1 s role in thermoregulation [33]. Administration of a topical TRPV1 antagonist markedly reduced scratching behavior, as well as erythema and edema, in atopic dermatitis mice models by day 12 of treatment, a finding previously supported by other murine studies [34,35]. Topical TRPV1 antagonist PAC-14028 has been assessed in phase II randomized controlled trials for the treatment of mild to moderate atopic dermatitis, showing significant reduction in pruritus-related VAS scores by week 8 [36].…”

An Atopic Dermatitis-Like Mouse Model by Alternate Epicutaneous Application of Dinitrofluorobenzene and an Extract of Dermatophagoides Farinae

“…However, the mechanism by which DNFB affects the effects of DfE remains unclear. DNFB-induced contact dermatitis may impair the skin barrier, and skin dendritic cells are more likely to capture external protein antigens through the damaged skin barrier ( 23 , 24 ). Immune modification by DNFB may be involved in this process ( 25 ).…”

IL-31: State of the Art for an Inflammation-Oriented Interleukin

“…Even the simplest method, nail clipping, leads to a decrease in pruritus and skin-barrier defects. In a study involving mice, immunofluorescence staining and Western blot results revealed that the antipruritic effect of nail clipping or the application of a plant-based topical treatment might be explained by the suppression of IL-31 [ 31 ]. This finding alone suggests the possible role of physical stimuli as triggering factors for the secretion of IL-31, although another interesting study suggested that even intense physical activity could lead to spikes in IL-31 production [ 32 ].…”