Abstract
The fibromyalgia syndrome (FMS) is characterized by chronic widespread pain, sleep disturbances, fatigue, and cognitive alterations. A limited efficacy of targeted treatment and a high FMS prevalence (2–5% of the adult population) sums up to high morbidity. Although, altered nociception has been explained with the central sensitization hypothesis, which may occur after neuropathy, its molecular mechanism is not understood. The marked female predominance among FMS patients is often attributed to a psychosocial predisposition of the female gender, but here we will focus on sex differences in neurobiological processes, specifically those of the immune system, as various immunological biomarkers are altered in FMS. The activation of innate immune sensors is compatible with a neuropathy or virus-induced autoimmune diseases. Considering sex differences in the immune system and the clustering of FMS with autoimmune diseases, we hypothesize that the female predominance in FMS is due to a neuropathy-induced autoimmune pathophysiology. We invite the scientific community to verify the autoimmune hypothesis for FMS.
Highlights
As long as the pathophysiology of the fibromyalgia syndrome (FMS) is not elucidated, the diagnosis (Wolfe et al, 2016; Arnold et al, 2019) and the treatment (Macfarlane et al, 2017) will remain inadequate
The history of FMS reveals the confusion (Inanici and Yunus, 2004) and the importance of (1) inflammation, (2) a neuropathic type of pain, (3) referred pain after irritation or damage of the paraspinal ligaments, (4) increased substance P levels in cerebrospinal fluid (CSF), and (5) an etiology of trauma and/or infection accompanied by mental stress, which are all consistent with neuroinflammation
The clinical profile of FMS displays a strong overlap with certain autoimmune diseases
Summary
As long as the pathophysiology of the FMS is not elucidated, the diagnosis (Wolfe et al, 2016; Arnold et al, 2019) and the treatment (Macfarlane et al, 2017) will remain inadequate. We propose that FMS is a neuropathy-induced autoimmune disease directed to nervous tissue. We describe the mechanisms of immunological selftolerance and how it can be breached, as well as the wellknown sex differences in the immune system, which explains why women are more susceptible to develop certain autoimmunity disorders.
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