Abstract
Fibromyalgia is a prevalent chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances, with high impact in quality of life. Despite extensive research, the pathophysiological mechanisms of fibromyalgia remain partially understood, complicating the diagnosis and treatment. Some evidence underscores the central role of abnormal pain processing, particularly central sensitization and defective descending pain modulation pathways. This review synthesizes and discusses current findings on the neurobiological underpinnings of pain in fibromyalgia, with focus on descending inhibitory control mechanisms and on the role of biomarkers. We integrate data from neurochemical, neuroimaging, and clinical studies to explain how impaired descending modulation contributes to enhanced pain sensitivity and discuss the putative biomarkers associated with changes in descending modulation. A better understanding of descending pain modulation dysfunction in fibromyalgia and related biomarkers is crucial for improving clinical outcomes and developing novel and more effective treatments.