Toward a Unified Neurobiological Framework for Fibromyalgia: Integrating Glutamate Dysregulation and Central Sensitization

Fibromyalgia presents with a heterogeneous constellation of sensory, cognitive, and affective symptoms that remain difficult to explain through peripheral mechanisms alone. Emerging evidence across chronic pain conditions identifies elevated glutamate concentrations, altered excitatory signaling, and central sensitization as key contributors to pain amplification, yet these processes are rarely integrated into a unified explanatory model. This hypothesis article proposes a central neurobiological framework in which glutamate-driven excitatory signaling, synaptic plasticity, and heightened central gain converge to produce the sensory amplification characteristic of fibromyalgia. By synthesizing neurochemical, neuroimaging, and pain processing findings, the model positions fibromyalgia within a broader class of centrally mediated pain disorders and outlines testable pathways for future mechanistic and clinical research. This integrative central framework aims to clarify the underlying basis of fibromyalgia’s diverse symptom profile and support more targeted approaches to assessment and treatment.