Transient Receptor Potential (TRP) Channels as Fundamental Regulators of Fibrosis and Pruritus—A New Therapeutic Target for Pathological Scar Management

TL;DR

This review explores how TRP channels might connect fibrosis and itching in scars, suggesting they could be a new target for treatment.

Contribution

The paper proposes TRP channels as a novel dual-target for managing fibrosis and pruritus in pathological scars.

Findings

TRP subfamilies TRPA1, TRPV1, TRPV3, and TRPV4 may link fibrosis and pruritus through inflammatory mediators.

Pharmacological targeting of TRP channels could offer a dual-pathway treatment for pathological scars.

Current TRP-targeted therapies face challenges like subtype selectivity and lack of clinical trials for scars.

Abstract

Pathological scars (PSs), which encompass hypertrophic scars (HSs and keloids, pose significant challenges in the realm of plastic surgery due to their characteristics of excessive fibrosis and persistent pruritus. This fibrosis can lead to both functional limitations and aesthetic issues, while pruritus often indicates ongoing scar development and greatly impacts quality of life. Although the underlying cause of both conditions is linked to dysregulated inflammation, the specific connections between fibrosis and pruritus are not well understood. Transient receptor potential channels (TRP), known for their roles in systemic fibrotic diseases and as mediators of chronic pruritus in skin disorders, may play a crucial role in the environment of pathological scars. This review compiles existing research to investigate the idea that certain TRP subfamilies (TRPA1, TRPV1, TRPV3, TRPV4) could link fibrosis and pruritus in pathological scars by interacting with common inflammatory mediators. We suggest that these channels might act as central molecular hubs that connect the signaling pathways of fibrosis and pruritus in these scars. Therefore, targeting TRP channels pharmacologically could be a promising approach to simultaneously alleviate both fibrosis and pruritus, potentially leading to a new dual-pathway treatment strategy for managing pathological scars. Our review also critically examines the current landscape of TRP-targeted therapies, pointing out challenges such as limited selectivity for specific subtypes and the lack of clinical trials focused on pathological scars, while emphasizing the necessity for interdisciplinary advancements in this area. In conclusion, while TRP channels are attractive targets for therapeutic intervention in pathological scars, their effective clinical application necessitates a more profound understanding of the mechanisms specific to scars and the creation of targeted delivery methods.

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