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Increased serotonin transporter availability in the brainstem of migraineurs

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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 123I-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 123I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, 123IADAM 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.

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Authors and Affiliations

  1. Dept. of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Sigrid Schuh-Hofer MD, Arno Villringer MD, Heike Israel, Rüdiger Wenzel MD & Guy Arnold MD

  2. Dept. of Neurology, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Sigrid Schuh-Hofer MD

  3. Clinic for Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Matthias Richter MD, Lilli Geworski PhD & Dieter Ludwig Munz MD

  4. Dept. of Neurology, Krankenhaus Sindelfingen, Sindelfingen, Germany

    Guy Arnold MD

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  1. Sigrid Schuh-Hofer MD
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  2. Matthias Richter MD
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Correspondence to Sigrid Schuh-Hofer MD.

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Schuh-Hofer, S., Richter, M., Geworski, L. et al. Increased serotonin transporter availability in the brainstem of migraineurs. J Neurol 254, 789–796 (2007). https://doi.org/10.1007/s00415-006-0444-0

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  • DOI: https://doi.org/10.1007/s00415-006-0444-0

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