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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Uppala Radhakrishna
1,*,
Murali R. Kuracha
2,
Iltefat Hamzavi
3,
Nazia Saiyed
4,
Jignesh Prajapati
5,
Rakesh M. Rawal
6,
Lavanya V. Uppala
7,
Giovanni Damiani
8,9,
Uppala Ratnamala
10 and
Swapan K. Nath
11
1
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
2
Department of Internal Medicine, University of Nebraska Medicine, Omaha, NE 68198, USA
3
Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202, USA
4
Department of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48076, USA
5
Department of Biochemistry & Forensic Sciences, Gujarat University, Ahmedabad 380009, India
6
Department of Botany, Bioinformatics and Climate Change Impacts Management, School of Science, Gujarat University, Ahmedabad 380006, India
7
Peter Kiewit Institute, College of Information Science & Technology, The University of Nebraska at Omaha, Omaha, NE 68182, USA
8
Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
9
Italian Center of Precision Medicine and Chronic Inflammation, University of Milan, 20122 Milan, Italy
10
Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad 380009, India
11
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
 
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*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(3), 1039; https://doi.org/10.3390/ijms26031039
Submission received: 18 December 2024 / Revised: 14 January 2025 / Accepted: 16 January 2025 / Published: 25 January 2025
(This article belongs to the Special Issue Molecular Basis and Treatment of Skin Diseases and Their Associated Complications)
Versions Notes

Abstract

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.
Keywords: epigenetics; hidradenitis suppurativa; biomarkers; chronic pain; bioinformatics epigenetics; hidradenitis suppurativa; biomarkers; chronic pain; bioinformatics

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MDPI and ACS Style

Radhakrishna, U.; Kuracha, M.R.; Hamzavi, I.; Saiyed, N.; Prajapati, J.; Rawal, R.M.; Uppala, L.V.; Damiani, G.; Ratnamala, U.; Nath, S.K. Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets. Int. J. Mol. Sci. 2025, 26, 1039. https://doi.org/10.3390/ijms26031039

AMA Style

Radhakrishna U, Kuracha MR, Hamzavi I, Saiyed N, Prajapati J, Rawal RM, Uppala LV, Damiani G, Ratnamala U, Nath SK. Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets. International Journal of Molecular Sciences. 2025; 26(3):1039. https://doi.org/10.3390/ijms26031039

Chicago/Turabian Style

Radhakrishna, Uppala, Murali R. Kuracha, Iltefat Hamzavi, Nazia Saiyed, Jignesh Prajapati, Rakesh M. Rawal, Lavanya V. Uppala, Giovanni Damiani, Uppala Ratnamala, and Swapan K. Nath. 2025. "Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets" International Journal of Molecular Sciences 26, no. 3: 1039. https://doi.org/10.3390/ijms26031039

APA Style

Radhakrishna, U., Kuracha, M. R., Hamzavi, I., Saiyed, N., Prajapati, J., Rawal, R. M., Uppala, L. V., Damiani, G., Ratnamala, U., & Nath, S. K. (2025). Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets. International Journal of Molecular Sciences, 26(3), 1039. https://doi.org/10.3390/ijms26031039

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