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Purpose of Review Recent studies have linked fibromyalgia (nociplastic pain) and depression to neuroinflammation. Restless legs syndrome (RLS) is highly prevalent in CWP (chronic widespread pain) and FMS (fibromyalgia syndrome) as well as in depression. This review focuses on evidence in the relationship between CWP and RLS and possible common pathophysiological mechanisms. Recent Findings CWP is chronic pain spread over various locations of the body and is a cardinal sign of fibromyalgia. Poor sleep quality is a common symptom in fibromyalgia as well as high levels of fatigue, poor cognition, and other associated features which include depression, headache, and abdominal pain. Evidence for a bilateral relationship between pain and sleep deficit is robust. The latest research focus is not only on insomnia symptoms in chronic pain but also on other types of sleep disorders such as RLS which is characterized by complaints of an “urge to move” frequently associated with dysesthesias. These sensations can also have painful characteristics. Thus, there is a possible overlap between these two entities. The high prevalence of RLS (33–54%) in CWP has been shown in several studies. The pathophysiological mechanisms behind CWP and RLS are still not completely known, but there is a rising amount of evidence on proinflammatory and neuroinflammatory processes in CWP. In RLS, there are links to dopaminergic dysfunction and more generally to monoaminergic dysfunctional circuits, BID (brain iron deficiency), altered glutamatergic neurotransmission, and genetic traits. Depression is a common comorbidity as well in CWP as RLS, and proinflammatory mechanisms have also been demonstrated in this condition. Summary The association between CWP and RLS is shown to be high and the pathogenesis of both conditions is still not completely understood. Recent research is focusing on proinflammatory and neuroinflammatory processes, not uniquely emerging in fibromyalgia/CWP, but inflammatory features have been found in depression as well as in sleep deficit. Proinflammatory/neuroinflammatory processes may be an underlying, common factor in both CWP and RLS that future research should investigate further.

(Neuro)Inflammatory Component May Be a Common Factor in Chronic Widespread Pain and Restless Legs Syndrome