Molecular insights into fibromyalgia: association of hub genes with pain targets, neuropathic pathways, and stress-related hormones

In Silico Pharmacol. 2026 May 7;14(2):135. doi: 10.1007/s40203-026-00636-1. eCollection 2026.

ABSTRACT

Fibromyalgia is a chronic musculoskeletal condition characterized by widespread pain, fatigue, and emotional dysregulation, with unclear pathophysiological mechanisms. In this bioinformatics-based analysis, gene expression data and protein-protein interaction (PPI) network analysis were used to identify differentially expressed genes (DEGs) associated with fibromyalgia. Among the identified 1050 DEGs, three hub genes-AGT, SNCA, and EZH2 emerged as potential key regulators of fibromyalgia progression. AGT, a key component of the renin-angiotensin system, is involved in blood pressure regulation, electrolyte balance, and neuroinflammatory processes, which may contribute to fatigue and heightened pain sensitivity in fibromyalgia. SNCA plays a role in synaptic dysfunction and central sensitization, key features of fibromyalgia's pain mechanisms. EZH2, an epigenetic regulator, modulates gene expression related to pain sensitization and neuroinflammation, emphasizing its significance in chronic pain pathways. These hub genes showed associations with pain targets, including BDNF, TAC1, and NGF, indicating their potential involvement in fibromyalgia-associated pain. Interactions with neuropathic pain genes in key brain regions-mPFC, NAc, and PAG-were observed; however, these associations are inferred from existing literature and were not directly measured in the present study. Additionally, connections to stress-related hormones, such as cortisol, dopamine, and serotonin, suggest that hormone-related gene expression changes may be associated with fibromyalgia symptoms, particularly pain sensitivity and emotional dysregulation. The downregulation of ESR2 and ABHD2, alongside the upregulation of SULT1E1, indicates potential alterations in estrogen-related pathways, which may be relevant to symptom severity, particularly in postmenopausal women. These findings, consistent with existing literature, suggest that AGT, SNCA, and EZH2 may serve as potential therapeutic targets, with EZH2 highlighted as an epigenetic regulator, and may provide a basis for future therapeutic exploration in fibromyalgia.

PMID:42109571 | PMC:PMC13153297 | DOI:10.1007/s40203-026-00636-1