In Vitro Study Of the Effects of the Menthoxypropanediol, an Anti-TRPM8, in the Atopic Dermatitis Pruritus

AD is a fairly common pathology whose prevalence in Western Europe and the United States is estimated at 10 to 15% in children and 4 to 7% in adults. This frequency has been steadily increasing for several decades. However, while the prevalence is increasing rapidly in emerging countries, a plateau has been observed for a few years in the industrialized countries with a maximum of 20% reached in Northern Europe.

The predominant symptom of AD is pruritus. It has a strong impact on the lives of patients both physically, psychologically and socially, which causes stress and sleep disorders. Because of this pruritus, sleep disturbances but also the displaying character of the disease, the quality of life of patients and their families is very often altered.

The pathophysiology of this chronic pathology and associated pruritus is complex and incompletely understood and current treatments are unfortunately only symptomatic.

Many receptors (TRPA1, TRPV1, PAR2 ...), molecules (neuromediators, neuropeptides, histamine ...) and secreted cytokines (IL-2, -4, -13 and -31, TSLP) are involved in the induction and mediation of chronic pruritus. Their role in pruritus associated with AD begins to be understood. Among them, the TRPM 8 has a particular interest. Indeed, this receptor belongs to the superfamily of the "potential transient receptor (TRP)" whose members are known to play a major role in sensory perceptions, including the perception of pruritus. TRPM8 is a thermoreceptor, activated by cold (T <28 ° C) or compounds such as menthol or derivatives, or eucalyptus and the beneficial action of menthol in the soothing of pruritus makes the TRPM8 receptor an attractive therapeutic target for treatment of pruritus in AD. Its role has never been studied in this context.

This project aims to study the role of TRPM8 in the pathophysiology of pruritus in AD in an in vitro model. Biopsies of atopic dermatitis patients (2/patient in pruritic skin lesion) will be put in culture and submit to topical application of menthoxypropanediol. The effect of this molecule on receptors involved in pruritus pathway will be assay (immunohistochemistry, QPCR).