Fibromyalgia beyond pain: a multisystemic dysregulation framework

Fibromyalgia (FM) is a prevalent and highly complex disease associated with a substantial reduction in quality of life and functional capacity, as well as significant use of healthcare resources. It is characterized by widespread pain, fatigue, sleep disturbances, and cognitive symptoms, among other manifestations. The heterogeneity of this symptomatology challenges traditional linear clinical models focused on the identification of overt structural damage. Based on a critical review of the contemporary literature, we argue that FM may represent the clinical expression of chronic dysregulation across multiple interacting physiological systems. Within this perspective, the peripheral nervous, central nervous, endocrine, and immune systems may influence central processes involved in nociceptive amplification, potentially contributing to the persistence of nociplastic pain states and the emergence of nonpain symptoms such as fatigue and cognitive dysfunction. Rather than replacing existing models, this perspective aims to expand them into a broader, nonreductionist framework that emphasizes systemic interactions and the loss of adaptive physiological coordination. Evidence was identified through PubMed/MEDLINE, Scopus, and Web of Science (2000-2026).