Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study

Abstract

Different to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our experiments demonstrated that phenoxyethanol induces skin misperception and uncomfortable skin sensations like itching and burning comparable to capsaicin via activating TRPV1. The stimulation was inhibited by blocking TRPV1 with ID1609. The present data strengthened hitherto studies that TRPV1 plays a critical role in sensitive skin.

TRP Channels in Skin Biology and Pathophysiology

“…Interestingly, TRPV1 immunoreactivity was lower in individuals with darker skin, suggesting that melanin might interfere with those factors that promote TRPV1 upregulation [67]. Perhaps related to these findings, the skin irritant phenoxyethanol was found to increase calcium influx into HaCaT cells in a manner inhibitable by TRPV1 antagonists [68]. Furthermore, it has been shown that retinoids evoke pain behavior in rodents by acting at TRPV1, presumably in neurons.…”

Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for cosmetic applications

“…Induction of hyperalgesic skin by the activation of the TRPV1 receptor with the chemical model substance capsaicin may seem to be quite an artificial system with poor practical relevance in the cosmetic field as no one would apply this compound to the skin without medical need. However, it has been shown that some chemical compounds relevant in cosmetics like phenoxyethanol or allergens can activate the TRPV1 receptor after a short lag time and a TRPV1 receptor blocker to prevent a burning and stinging perception induced by chemical compounds is therefore of an advantage.…”

“…However, it has been shown that some chemical compounds relevant in cosmetics like phenoxyethanol or allergens can activate the TRPV1 receptor after a short lag time [6] and a TRPV1 receptor blocker to prevent a burning and stinging perception induced by chemical compounds is therefore of an advantage.…”

“…As such, chemical compounds like capsaicin which trigger the open state of the channel lead to burning sensations. Interestingly, a continuous or repeated stimulus with this compound causes a downregulation of the TRPV1 receptor and a desensitization, whereas stimulation with, for example, phenoxyethanol does not . In contrast, acid application increases the expression of TRPV1 .…”

“…Typically, two molecules of a binder are sufficient to induce the conformational change . Potent TRPV1 receptor blockers with convincing in vitro and in vivo data exist . However, an inhibitory effect on temperature dependent activation in vivo has not yet been demonstrated for TRPV1 receptor blockers in cosmetic use.…”