Increased serotonin transporter availability in the brainstem of migraineurs

For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central seroto-nergic system is located in the raphe nuclei and the adjacent reticular formation in the brain-stem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand 12 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 co-registered 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, 23 I- ADAM 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.