Possible Molecular Mediators Involved and Mechanistic Insight into Fibromyalgia and Associated Co-morbidities

Abstract

Fibromyalgia is a chronic complex syndrome of non-articulate origin characterized by musculoskeletal pain, painful tender points, sleep problems and co-morbidities including depression, migraine. The etiopathogenesis of fibromyalgia is complex, variable and remains inconclusive. The etiological factors that have been defined include stress, genetic predisposition and environmental components. As per the reports of the American College of Rheumatology (ACR) the prevalence of fibromyalgia varies from 2 to 22% among the general population with poor diagnostic features primarily pain. Fibromyalgia encompasses a spectrum of co-morbid conditions with multifarious pathogenesis. The highly prevalent manifestations of fibromyalgia include heterogeneous pain and aches. Biochemical and neurobiological elements of fibromyalgia include neurotransmitters, hypothalamic pituitary adrenal axis (HPA axis), inflammatory cytokines, monoaminergic pathway, opioid peptides, sex hormones, nerve growth factor (NGF) and local free radical insult. An imbalance in the serotonergic system is the major underlying etiological factor that has been explored most widely. Owing to complex interplay of diverse pathophysiological pathways, overlapping co-morbidities such as depression have been clinically observed. Therapeutic management of fibromyalgia involves both non pharmacological and pharmacological measures. The current review presents various dysregulations and their association with symptoms of fibromyalgia along with their underlying neurobiological aspects.

Keywords: Chronic hepatitis C virus; Cytokines; Depression; Fibromyalgia; Inflammatory bowel disease; Migraine; Pain; Serotonin; Sleep.