Epigenetic Modification in Preclinical and Clinical Dermatological Itch Conditions.

Abstract

<h4>Background and objective</h4>In recent years, studies have suggested an epigenetic fingerprint related to specific diseases and pathological conditions characterised by itch. Epigenetics, defined as modifications that regulate gene expression without altering the DNA sequence, has previously been shown to be involved in pain, but its association with itch remains poorly investigated. This review aims to summarise the current knowledge regarding the involvement of epigenetic modifications in preclinical models and clinical dermatological itch conditions.<h4>Databases and data treatment</h4>English-language studies were identified through PubMed and Google Scholar using Medical Subject Heading (MeSH) terms related to itch or pruritus and epigenetics or DNA methylation or histone modification or microRNA or lncRNA or circRNA or non-coding RNA, from inception to January 2025. Non-relevant publications and non-peer-reviewed formats were excluded. Reference lists were also screened for additional studies.<h4>Results</h4>Both preclinical and clinical studies indicate that DNA methylation is involved in the regulation of itch in atopic dermatitis and other pruritic skin conditions, and histone deacetylase inhibitors have the effect of alleviating pruritus. Among miR-711, miR-203b-3p, and miR-let-7b, identified as mediators of itch in animal models, miR-711 and miR-203 were also upregulated in certain clinical models.<h4>Conclusions</h4>A clear association between itch and epigenetic modifications has been demonstrated in both preclinical skin disease models and clinical dermatological conditions. Several of these changes appear consistently across experimental and human studies, suggesting their role as shared molecular regulators of itch.<h4>Significance statement</h4>Current understanding of the underlying mechanisms of itch remains limited, and optimal treatments for chronic itch have been difficult to develop. Epigenetic modifications in the pathophysiology of itch may contribute to our understanding of itch pathways and pave the way for new, potential treatments.