• Y Sakai, C Dobson, M Diksic, M Aubé, and E Hamel.
• Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
• Neurology. 2008 Feb 5;70(6):431-9.

BackgroundAltered serotonin (5-HT) neurotransmission has been implicated in the pathophysiology of migraine headache.ObjectivesTo test this hypothesis in migraine patients in vivo using PET and alpha-[(11)C]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.MethodsSix patients were scanned 1) within 6 hours after the onset of a spontaneous migraine attack, 2) 2 hours 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.ResultsBrain 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%).ConclusionsThese 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.

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