Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets

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Hidradenitis suppurativa (HS) is a chronic skin condition that primarily affects areas with dense hair follicles and apocrine sweat glands, such as the underarms, groin, buttocks, and lower breasts. Intense pain and discomfort in HS have been commonly noted, primarily due to the lesions’ effects on nearby tissues. Pain is a factor that can influence DNA methylation patterns, though its exact role in HS is not fully understood. We aim to identify molecular markers of chronic pain in HS patients. We performed DNA methylome of peripheral blood DNA derived from a group of 24 patients with HS and 24 healthy controls, using Illumina methylation array chips. We identified 253 significantly differentially methylated CpG sites across 253 distinct genes regulating pain sensitization in HS, including 224 hypomethylated and 29 hypermethylated sites. Several genes with pleiotropic roles include transporters (ABCC2, SLC39A8, SLC39A9), wound healing (MIR132, FGF2, PDGFC), ion channel regulators (CACNA1C, SCN1A), oxidative stress mediators (SCN8A, DRD2, DNMT1), cytochromes (CYP19A, CYP1A2), cytokines (TGFB1, IL4), telomere regulators (CSNK1D, SMAD3, MTA1), circadian rhythm (IL1R2, ABCG1, RORA), ultradian rhythms (PHACTR1, TSC2, ULK1), hormonal regulation (PPARA, NR3C1, ESR2), and the serotonin system (HTR1D, HTR1E, HTR3C, HTR4, TPH2). They also play roles in glucose metabolism (POMC, IRS1, GNAS) and obesity (DRD2, FAAH, MMP2). Gene ontology and pathway enrichment analysis identified 43 pathways, including calcium signaling, cocaine addiction, and nicotine addiction. This study identified multiple differentially methylated genes involved in chronic pain in HS, which may serve as biomarkers and therapeutic targets. Understanding their epigenetic regulation is crucial for personalized pain management and could enhance the identification of high-risk patients, leading to better preventative therapies and improved maternal and neonatal outcomes.