The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome

ObjectiveBased upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in RLS patients and controls.MethodsForty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), alpha-MSH, beta-MSH, and beta-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale.ResultsRLS participants were 52.7 +/- 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 +/- 9.0. Controls had similar age and sex. Plasma ACTH, alpha-MSH, and beta-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 +/- 11.5 vs 12.7 +/- 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF beta-MSH was significantly higher in painful than nonpainful RLS or controls (48.2 +/- 24.8 vs 32.1 +/- 14.8 vs 32.6 +/- 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF alpha-MSH was higher in RLS than controls (34.2 +/- 40.9 vs 20.3 +/- 11.0pg/ml, p = 0.062). CSF beta-EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 +/- 3.4 vs 10.8 +/- 3.1 vs 12.3 +/- 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF alpha- and beta-MSH to CSF beta-endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007).InterpretationCSF beta-MSH is increased and CSF beta-endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024