title: The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study.
abstract: Opioids have been shown to provide symptomatic relief from dysaesthesias and motor symptoms in restless legs syndrome (RLS). However, the mechanisms by which endogenous opioids contribute to the pathophysiology of RLS remain unknown. We have studied opioid receptor availability in 15 patients with primary RLS and 12 age-matched healthy volunteers using PET and [11C]diprenorphine, a non-selective opioid receptor radioligand. Ligand binding was quantified by generating parametric images of volume of distribution (V(d)) using a plasma-derived input function. Statistical parametric mapping (SPM) was used to localize mean group differences between patients and controls and to correlate ligand binding with clinical scores of disease severity. There were no mean group differences in opioid receptor binding between patients and controls. However, we found regional negative correlations between ligand binding and RLS severity (international restless legs scale, IRLS) in areas serving the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex and orbitofrontal cortex). Pain scores (affective component of the McGill Pain Questionnaire) correlated inversely with opioid receptor binding in orbitofrontal cortex and anterior cingulate gyrus. Our findings suggest that, the more severe the RLS, the greater the release of endogenous opioids within the medial pain system. We therefore discuss a possible role for opioids in the pathophysiology of RLS with respect to sensory and motor symptoms.
authors.affiliation: Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK. sarah.v.s@gmx.de
authors.forename: Sarah
authors.initials: S
authors.lastname: von Spiczak
authors.forename: Alan L
authors.initials: AL
authors.lastname: Whone
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Asselin
authors.forename: Federico
authors.initials: F
authors.lastname: Turkheimer
authors.forename: Tobias
authors.initials: T
authors.lastname: Tings
authors.forename: Svenja
authors.initials: S
authors.lastname: Happe
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
mesh_terms: D000328:Adult; D000368:Aged; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D004174:Diprenorphine; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000502:physiology*; D010147:Pain Measurement; D049268:Positron-Emission Tomography / Q000379:methods; D012148:Restless Legs Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D002250:Carbon Radioisotopes; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D004174:Diprenorphine