Inhibition of TRPV1 for the treatment of sensitive skin

Abstract

During the past years, the topic sensitive skin became one of the most important fields in dermatology. The tremendous interest is based on several studies showing that about 50% of the population declares to have sensitive skin. The human thermoreceptor hTRPV1 was previously identified to contribute to this skin condition while facilitating neurogenic inflammation leading to hyperalgesia. Furthermore, skin sensitivity towards capsaicin, a natural activator of TRPV1, was shown to correlate with sensitive skin. In a screening campaign based on recombinant HEK293-cells stably transfected with hTRPV1, the selective antagonist trans-4-tert-butylcyclohexanol was identified. This antagonist is able to inhibit capsaicin-induced hTRPV1 activation with an IC(50) value of 34 ± 5 μm tested in HEK293-cells as well as in electrophysiological recordings performed in oocytes expressing hTRPV1. Strikingly, in a clinical study with 30 women using topical treatment with o/w emulsions containing 31.6 ppm capsaicin, we were able to show that 0.4% of this inhibitor significantly reduces capsaicin-induced burning (P < 0.0001) in vivo. Thus trans-4-tert-butylcyclohexanol has the potential as a novel bioactive for the treatment of sensitive skin.

The evaluation of neural and vascular hyper‐reactivity for sensitive skin

“…And the genetic variation of TRPV1 and sensory irritation to capsaicin demonstrate that TRPV1 play an important role in pathogenesis of sensitive skin (33). Our results supported that sensory irritation inhibitors and anti-inflammatory compounds should be considered to be added in cosmetics to reduce the heighted neural and vascular reaction of sensitive skin.…”

What Is Sensitive Skin? A Systematic Literature Review of Objective Measurements

“…It is known that whenever skin is challenged by capsaicin, noxious heat or low pH, transient receptor potential vanilloid 1 (TRPV1) is activated [45,46], resulting in nociceptor-mediated burning pain. An overexpression of this ion channel could play a key role in the pathophysiology of sensitive skin, as its inhibition results in reduced burning sensation following capsaicin application [47]. Differences in pain perceptions were also observed in subjects with sensitive skin by fMRI.…”

Sensitive skin

“…The use of well-tolerated cosmetics or cosmetics with soothing effects has been recommended. For example, trans-4-tert-butylcyclohexanol, a selective antagonist of TRPV1, has recently been proposed [56]. However, the number of products that have been proposed is very high.…”