Fibromyalgia as a Neuroimmune-Psychiatric Disorder

Fibromyalgia (FM) is a chronic disorder characterized by widespread allodynia and hyperalgesia, comorbid fatigue, cognitive impairment, and sleep disruption. It is characterized by central sensitization, which is one of the main mechanisms and an essential feature of altered pain-processing system at the level of the central nervous system (CNS), and is an example of a disorder of pain regulation affected by genetic, environmental and neurobiological factors. Another series of brain imaging studies demonstrate increased sensitivity to experimental pain stimuli, altered neurotransmitter function, and changes in resting-state functional connectivity. While FM has traditionally been considered a musculoskeletal disorder, an increasing number of studies suggest that FM should rather be viewed as a neuroimmune-psychiatric disorder, characterized by the dysregulation of the CNS, immune system and stress response pathways. Central sensitization developed in the presence of pro-inflammatory cytokines, altered cytokine profiles and neuroinflammation, and glial cell activation. The prevalence of psychiatric comorbidities, such as depression, anxiety and post-traumatic stress disorder (PTSD), is also high in FM. This paper discusses the neuroimmune pathways underlying FM, the commensurate pathways that connect FM and psychiatric illnesses, and recent treatment approaches, primarily focusing on pharmacological and non-pharmacological strategies to address impaired neuroimmune functioning as well as the psychiatric dimensions of FM. Viewing FM as an alteration of homeostasis may facilitate developing improved, multi-disciplinary treatment protocols.