Cutaneous neurogenic inflammation mediated by TRPV1–NGF–TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites

Abstract

BackgroundRosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers.ObjectivesWe investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation.MethodsWe examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea‐like mouse model was generated by the injection of the 37‐amino acid C‐terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined.ResultsIncreased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea‐like mouse model.ConclusionsThe findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF–TrkA–TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

Cell-Free Adipose Tissue Extracts: A Novel Approach to Downregulate TRPV1 for Rosacea Treatment

“…The HaCaT cell line is a representative epithelial keratinocyte used in rosacea experiments 26,28 . In rosacea patients, keratinocytes are activated by pervading antigens in impaired skin barrier and then, aggravate an upregulated TRPV1 receptor, which further degenerate inflammation and telangiectasia 10 , 29 . Furthermore, LL37 cathepsin is the most widely used method to establish animal models of rosacea.…”

Randomised, split‐face study of a dermocosmetic cream containing Sphingobioma xenophaga extract and Neurosensine® in subjects with rosacea associated with erythema and sensitive skin

“…1 Rosacea is associated with a microbiome dysbiosis with increase in Demodex mites and expression of transient receptor potential cation channel subfamily V member 1 TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), triggering cutaneous neurogenic inflammation. 5 Rosacea associated with erythema and flushing and burning sensation refractory to traditional treatment may be designated as neurogenic rosacea. 6 A specific dermocosmetic cream (DC cream, Toleriane Rosaliac ® AR concentrate cream, La Roche-Posay Laboratoire Dermatologique, France) containing acetyl dipeptide-1 cetyl ester (Neurosensine ® ), a soothing compound that acts on skin sensitivity by decreasing erythema and irritation as well as reducing signs related to neurogenic inflammation, and shea butter to moisturise the skin barrier, has been developed for rosacea patients.…”

“…Rosacea is associated with a microbiome dysbiosis with increase in Demodex mites and expression of transient receptor potential cation channel subfamily V member 1 TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), triggering cutaneous neurogenic inflammation. 5 Rosacea associated with erythema and flushing and burning sensation refractory to traditional treatment may be designated as neurogenic rosacea. 6 …”