Not So Vanilla: What Dermatologists Should Know About Vanilloid Receptors

December 2023 | Volume 22 | Issue 12 | 1237 | Copyright © December 2023


Published online November 21, 2023

Cleo Whiting BAa, Sara Abdel Azim MSa,b, Adam Friedman MD FAADa

aDepartment of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC
bGeorgetown University School of Medicine, Washington, DC

TRPV Channels and Dermatologic Disease
Rosacea
Given the various environmental triggers for rosacea, much research has been devoted to elucidating the involvement of TRP channels in rosacea pathophysiology. Across different subtypes of rosacea mast cells were found to colocalize with TRPV2 and TRPV4 and, while mRNA levels of TRPV1, TRPV2, and TRPV3 were found to be elevated in all subtypes, TRPV2, TRPV3 and TRPV4 were found to be differentially expressed.11 Moreover, TRPV4 plays a significant role in mast cell activation in rosacea.12 

Atopic Dermatitis
Neuroinflammation is strongly associated with AD. Histologically, AD lesions have increased SP- and CGRP-positive cutaneous sensory nerve fibers and, compared to normal controls, increased contacts between mast cells and nerve fibers are found within both lesional and non-lesional skin.13 Altogether, these findings support the initiation and maintenance of neurogenic inflammation through mast cell activation and induction of cytokine release by keratinocytes by SP and CGRP. Furthermore, the Type 2 helper T cell (Th2) derived cytokine IL-31 directly activates TRPV1+/TRPA1+ sensory nerves in the skin of AD patients.14 

Sensitive Skin Syndrome
Sensitive skin syndrome (SSS) is characterized by transient sensory perceptions (burning, tingling, stinging, pain, itching) invoked by otherwise innocuous stimuli. The pathogenesis is not completely understood although it is considered a neuropathic disorder.15,16 Environmental factors such as temperature change are well-known triggers.17 Given this information, it is suggested that SSS is a result of sensitization of TRPV1 expressed on cutaneous sensory nerves by the inflammatory neuropeptides endothelin-1 and nerve growth factor, ultimately leading to impaired barrier function and decreased thresholds for sensory nerve receptor activation.18

CONCLUSION & EMERGING THERAPEUTICS

Topical formulations containing Asivastrep, Pegcantratinib, and ASN008 compounds targeting TRPV1 are promising avenues for treating chronic pruritus and AD.19 A phase IIb clinical trial demonstrated that Asivastrep cream has superior effectiveness in reducing inflammation and pruritus than placebo cream, though further evaluation of efficacy and safety in larger-scale phase III trials is necessary.20 The findings from the PAC-14028 cream trials similarly highlighted significant improvements in AD symptoms, without notable safety concerns.21 Additionally, applying synthetic peptides targeting TRPV1 for UV-induced skin responses holds promise for addressing inflammation and photoaging.22 These developments offer alternative therapeutic options for patients seeking non-steroidal medications with a favorable side effect profile.

Disclosure
CW's work is funded through an independent fellowship grant from Galderma; SAA's work is funded through independent fellowship grants from Lilly and Pfizer. AF has no conflicts of interest to declare.
 

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AUTHOR CORRESPONDENCE

Adam Friedman MD FAAD ajfriedman@mfa.gwu.edu
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