Fibromyalgia syndrome in need of effective treatments

Abstract

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.

Fig. 1.

Diagram representation of the proposed steps involved in the pathogenesis of FMS and targets for treatment. Stress peptides (CRH, nerve growth factor, neurotensin, SP) are released from the spinal cord in peripheral tissues (blood vessels, muscles, skin) in response to allergic, environmental, immune, infectious, and stress triggers (blue box). There, they act synergistically with IL-33 to stimulate mast cells, which secrete inflammatory and neurosensitizing molecules such asCRH, histamine, bradykinin, IL-1, IL-6, prostaglandin D2, and TNF (green box). These molecules can either activate peripheral sensory nerves directly or reach the brain through the systemic circulation, thus creating a self-sustaining pain circuit. Treatment approaches (white box) include exercise and relaxation to reduce stress (specific norepinephrine reuptake inhibitors (SNRIs); specific serotonin reuptake inhibitors (SSRIs); tricyclic antidepressants (TCAs) to reduce anxiety and depression; as well as TCAs and antiseizure medications to provide analgesia. Finally, luteolin and related compounds can inhibit the release of MC mediators.