Pathogenetic and clinical aspects of fibromyalgia: one year in review 2026

Fibromyalgia (FM) is a complex chronic pain condition with a multifaceted pathogenesis and heterogeneous clinical presentation. This narrative review summarises the most relevant studies published in 2025 on the pathogenetic and clinical aspects of FM. Central sensitisation remains the main neurobiological mechanism, supported by evidence of increased ascending nociceptive signalling, impaired descending inhibition, network reorganisation and autonomic dysfunction. Emerging findings have also explored a possible role for non-classical autoimmune mechanisms, as patient-derived IgG has been shown to induce pain hypersensitivity and bind dorsal root ganglion neurons and satellite glial cells, suggesting potential interactions between immune and metabolic pathways. The gut microbiome is increasingly implicated, showing reduced diversity, distinct signatures, and transferable pain phenotypes. Genetic studies identify a predominantly neuronal architecture involving 26 loci linked to proteins essential for neuronal function. Oxidative stress remains a major hypothesis, supported by elevated biomarkers and preclinical evidence for mitochondrial-targeted strategies. Early-life stress may selectively affect the right amygdala, contributing to long-term vulnerability. Clinically, pain in FM appears heterogeneous and may not be entirely explained by a purely nociplastic paradigm, as some studies have suggested the presence of neuropathic-like features in at least a subset of patients. Likewise, residual pain in inflammatory arthritis remains a multifactorial and incompletely characterised entity, potentially sharing some mechanisms with FM while also encompassing distinct and broader pathophysiological processes. Cognitive dysfunction (fibrofog) represents a multidimensional clinical construct whose underlying mechanisms remain only partially understood. FM is also associated with high affective burden, systemic symptoms, and reduced muscle performance consistent with dynapenia. Stigma and symptom invisibility continue to negatively affect care, while sex and gender influence disease expression and burden. Digital health and AI offer new opportunities but also raise concerns regarding misinformation. Overall, current evidence supports a multidimensional view of FM and highlights the need for updated diagnostic criteria and more integrated, personalised models of care.