ArticleBrain : a journal of neurology2024
Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.
Article in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Periodic limb movements during sedation and general anesthesia in elderly patients: a prospective observational study.Journal of clinical monitoring and computing · 2026Observational
- Restless Legs Syndrome: A Network Model of Iron-Dependent Neuromodulation-A Narrative Review.Brain sciences · 2026Review
- The evolving treatment landscape of restless legs syndrome.Therapeutic advances in neurological disorders · 2026Review
- Restless legs syndrome and periodic limb movements of sleep - the relationship with stroke and other cerebrovascular disease.Nature reviews. Neurology · 2026Review
- Multidimensional iron dysmetabolism and gut-brain axis interactions in restless legs syndrome: from peripheral deficiency to central dysregulation.Frontiers in aging neuroscience · 2026Review
- Neural Correlates of Restless Legs Syndrome (RLS) Based on Electroencephalogram (EEG)-A Mechanistic Review.International journal of molecular sciences · 2025Review
- Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome.Brain, behavior, & immunity - health · 2025Article
- Targeting the Opioid System in Cardiovascular Disease: Liver Proteomic and Lipid Profile Effects of Naloxone in Atherosclerosis.Biomedicines · 2025Article
- Evidence of Involvement of the Calcitonin Gene-Related Peptide in Restless Legs Syndrome.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Sleep Disorders in a Sample of Patients with Pediatric-Onset Multiple Sclerosis: Focus on Restless Legs Syndrome.Journal of clinical medicine · 2025Article
- Association between inflammatory cytokines and disease severity in restless legs syndrome.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Review
- Restless legs syndrome, neuroleptic-induced akathisia, and the iron opioid dopamine link.Sleep · 2024Article
- Diffusion prepared pseudo-continuous arterial spin labeling reveals blood-brain barrier dysfunction in patients with CADASIL.European radiology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 9 institutions in 3 countries.
Funding
Abstract
Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.
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