title: Increased serotonin transporter availability in the brainstem of migraineurs.
abstract: For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central serotonergic system is located in the raphe nuclei and the adjacent reticular formation in the brainstem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand (123)I-ADAM [2-((2-((dimethylamino) methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine serotonergic system being involved in the pathophysiology of migraine. Nineteen migraine patients and 10 healthy, age- and sex-matched controls were enrolled. The neuroimaging study was performed interictally during the pain-free interval. Single Photon Emission Computed Tomography (SPECT)-images were coregistered with MRI-scans. Region of interest (ROI)-analysis revealed a highly significant increase of (123)I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, (123)IADAM uptake in the thalamus did not differ significantly between migraineurs and controls. Our study demonstrates for the first time a significant increase of brainstem SERT-availability in migraineurs, suggesting a dysregulation of the brainstem serotonergic system. It remains to be elucidated whether the altered SERT-availability is causally related to migraine pathophysiology or whether it reflects secondary pathophysiological mechanisms.
authors.affiliation: Dept. of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany. sigrid.schuh-hofer@gmx.net
authors.forename: Sigrid
authors.initials: S
authors.lastname: Schuh-Hofer
authors.forename: Matthias
authors.initials: M
authors.lastname: Richter
authors.forename: Lilli
authors.initials: L
authors.lastname: Geworski
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.forename: Heike
authors.initials: H
authors.lastname: Israel
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Wenzel
authors.forename: Dieter Ludwig
authors.initials: DL
authors.lastname: Munz
authors.forename: Guy
authors.initials: G
authors.lastname: Arnold
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D002928:Cinanserin; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D008881:Migraine Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D011149:Pons / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D002928:Cinanserin