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

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.

The effects of photobiomodulation therapy on inflammatory mediators, immune infiltration, and angiogenesis in a mouse model of rosacea.

Background: Rosacea is a chronic skin disorder with increasing prevalence and challenging management. Photobiomodulation therapy (PBMT) may be a promising adjuvant treatment for rosacea. Methods: This study investigated the efficacy of PBMT for the treatment of rosacea lesions in a well-established mouse model using a combination of wavelengths at 590 and 830 nm. Female BALB/c mice were randomized into three groups, namely, a negative control (NC) group, a model control (MC) group, and a PBMT group. Mice were injected with LL-37 or normal saline for construction of the model and NCs, respectively. Mice in the PBMT group were administered PBMT at wavelengths of 590 nm (25 mW) and 830 nm (50 mW). The severity of erythema, inflammatory cell counts, the expression of key inflammatory mediators, and the degree of angiogenesis and immune cell infiltration of the skin lesions were evaluated by hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence staining. Results: PBMT significantly decreased the erythema scores and inflammatory cell infiltration of rosacea lesions in mice. Further studies revealed that PBMT downregulated the increased expression of inflammatory mediators (S100A9 and p65) and angiogenesis markers (CD31), and attenuated the dysregulation of immune cell infiltration [including neutrophils, regulatory T cells (Treg cells), γδ T cells, and macrophages] in mice with rosacea. Conclusions: This investigation suggested that PBMT can improve the rosacea condition by regulating key inflammatory mediators and dysregulating immune infiltration and angiogenesis.