title: Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study.
abstract: BACKGROUND
  Phenoxyethanol is a widely used preservative in personal care products. Transient receptor potential vanilloid 1 (TRPV1) on cell membrane is activated by TRPV1 agonist capsaicin resulting in an opening of the channel for calcium influx, which is linked with neurosensory sensations characterized by itching, burning and stinging of skin. Whether uncomfortable skin sensations caused by phenoxyethanol claimed by people having sensitive skin are also due to activation of TRPV1 has not been reported in the literature.
  
  
  OBJECTIVE
  The aim of this study was to evaluate whether the TRPV1 is involved in the induction of itching and burning sensation by phenoxyethanol.
  
  
  METHODS
  The effect of phenoxyethanol on TRPV1 was assessed in vitro on HaCaT cells. The activation of TRPV1 and its inhibition by a TRPV1 antagonist were evaluated by cellular calcium influx. TRPV1 protein expression was also investigated by Western blot. In vivo in a split-face study, phenoxyethanol formulated at 1% was compared to a formulation additionally containing a TRPV1 antagonist. By applying the formulations to the nasolabial fold, the scores of phenoxyethanol-induced sensations were compared to those of the TRPV1 antagonist.
  
  
  RESULTS
  In vitro phenoxyethanol induced calcium influx in HaCaT cells in a dose-dependent manner after 20 min. This effect was abolished by a solution containing the TRPV1 antagonist trans-tert-butyl cyclohexanol (ID1609). Phenoxyethanol had no effect on the expression of TRPV1, whereas capsaicin caused a significant downregulation of this receptor in the same experiment. In vivo 1% phenoxyethanol induced a skin burning and itching sensation in a cohort of 60 of 243 Chinese female subjects being sensitive to phenoxyethanol discomfort. The uncomfortable skin sensations were significantly inhibited by ID1609.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shanxi, China.|Department of Dermatology, The Air Force General Hospital of PLA, Fucheng Road No. 30, Beijing, China.
authors.forename: D-G
authors.initials: DG
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Fucheng Road No. 30, Beijing, China.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Du
authors.affiliation: Explorative Reseach Scent & Care, Innovation Life Essentials, Symrise Co. Lt, Muhlenfeldstr, Holzminden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Gerhard
authors.affiliation: Explorative Reseach Scent & Care, Innovation Life Essentials, Symrise Co. Lt, Muhlenfeldstr, Holzminden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Imke
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Fucheng Road No. 30, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004311:Double-Blind Method; D005026:Ethylene Glycols / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants / Q000008:administration & dosage*; D010919:Placebos; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D005026:Ethylene Glycols; D007509:Irritants; D010919:Placebos; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C005398:phenoxyethanol; D002118:Calcium
keywords: TRPV1; TRPV1 antagonist; calcium influx; capsaicin; phenoxyethanol; sensitive skin; skin burning; skin itching