Sumatriptan normalizes the migraine attack-related increase in brain serotonin synthesis

Background: Altered serotonin (5-HT) neurotransmission has been implicated in the pathophysiology of migraine headache. Objectives: To test this hypothesis in migraine patients in vivo using PET and alpha-[C-11] methyl-L-tryptophan as a surrogate marker of brain 5-HT synthetic rate during different phases of their migraine attack and after acute antimigraine therapy with sumatriptan, and to compare them with normal controls. Methods: Six patients were scanned 1) within 6 hours after the onset of a spontaneous migraine attack, 2) 2hours after subcutaneous sumatriptan, and 3) interictally when migraine free for at least 3 days. Head pain was rated before each scan, and before and every 15 minutes after sumatriptan. Results: Brain 5-HT synthesis was highest during attacks, lowest after sumatriptan, and intermediate when patients were migraine free. All states were statistically different from the others in virtually all brain regions examined. 5-HT synthetic rates in patients during migraine attacks did not differ from those of age-and sex-matched controls, whereas they were significantly lower after sumatriptan in a majority of regions. Interictally, global brain 5-HT synthetic rate was slightly, albeit not significantly, lower (-14%) in migraine patients than in controls, with specific cortical areas exhibiting proportionally more severe reductions (-28% to 31%). Conclusions: These findings point to a low cortical serotonergic tone in migraine patients interictally. Further, they demonstrate widespread increases in brain serotonin (5-HT) synthetic rate in migraine patients during attacks, and that triptans exert a negative feedback regulation of brain 5-HT synthesis concurrently with modulation of pain pathways.