Fibromyalgia: one year in review 2025.
Cristina Iannuccelli, Martina Favretti, Giulio Dolcini, Marco Di Carlo, Greta Pellegrino, Laura Bazzichi, Fabiola Atzeni, Daniela Lucini, Giustino Varassi, Matteo Luigi Giuseppe Leoni, Diego Maria Michele Fornasari, Fabrizio Conti, Fausto Salaffi, Piercarlo Sarzi-puttini, Manuela Di Franco
Clinical and experimental rheumatology June 1, 2025 Peer reviewed DOI: 10.55563/clinexprheumatol/buhd2z via PubMed
Summary
Fibromyalgia is a chronic pain syndrome whose causes and treatments are still not fully understood. In 2024, research highlights dysregulation of stress-response systems, low-grade inflammation, gut microbiota changes, and mitochondrial dysfunction as key factors. Brain imaging shows distinct patterns in fibromyalgia compared to other pain disorders. New diagnostic approaches include multi-omics. Clinical attention is growing for under-recognized issues like sexual and cognitive problems, and for overlaps with long COVID. Non-pharmacological therapies like exercise and psychosocial support remain central, while neuromodulation, psychedelics, and technologies such as virtual reality and AI offer new possibilities.
Study at a glance
| Design | review |
|---|---|
| Key finding | Fibromyalgia involves dysregulation of stress and immune systems, mitochondrial dysfunction, and distinct brain changes; non-pharmacological therapies remain fundamental, while emerging treatments include neuromodulation, psychedelics, and digital technologies. |
Abstract
Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.