The temperature-sensitive receptors TRPV4 and TRPM8 have important roles in the pruritus of rosacea

J Dermatol Sci. 2022 Nov;108(2):68-76. doi: 10.1016/j.jdermsci.2022.11.004. Epub 2022 Nov 30.

Abstract

Background: Certain sensations are the secondary phenotypes of rosacea and affect patients' quality of life. Transient receptor potential (TRP) channels may be involved in its occurrence. However, there is a lack of research independently discussing itch in rosacea.

Objectives: Our study aimed to investigate risk factors for pruritus in rosacea patients and to discover the molecular mechanism of pruritus.

Methods: A binary logistic regression model was used to identify significant variables affecting pruritus in 782 rosacea patients. The LL-37 was injected intradermally into the face of mice to establish the animal model. qRT-PCR, immunohistochemistry and immunofluorescence were used to analyse the expression differences in pruritus-related molecules in mouse skin and the corresponding trigeminal ganglion (TG) between pruritus and nonpruritus groups.

Results: The incidence of pruritus in rosacea was 42.46%, and the incidence of other symptoms increased with pruritus. Temperature effects were prominently related to the itch sensation of rosacea. Intradermal injection of LL-37 not only caused rosacea-like facial lesions but also induced a behavioural pattern indicative of pruritus. Increased expression of the temperature-sensitive receptors TRPV4 and TRPM8 was found in pruritic mouse skin and TG and human skin samples.

Conclusions: In rosacea patients, pruritus occurs frequently along with burning, flushing and sensitivity, most likely due to changes in temperature. The temperature-sensitive receptors TRPV4 and TRPM8 are both involved in the mechanism of pruritus in rosacea.

Keywords: Pruritus; Rosacea; TRPM8; TRPV4; Temperature-sensitive.

MeSH terms

  • Animals
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Pruritus / pathology
  • Quality of Life
  • Rosacea* / complications
  • Rosacea* / pathology
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism
  • TRPV Cation Channels* / genetics
  • TRPV Cation Channels* / metabolism
  • Temperature

Substances

  • Membrane Proteins
  • TRPM Cation Channels
  • TRPM8 channel-associated factor 1 protein, human
  • TRPM8 protein, human
  • TRPM8 protein, mouse
  • TRPV Cation Channels
  • TRPV4 protein, human
  • Trpv4 protein, mouse