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.


OBJECTIVE
To 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.


METHODS
Six 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.


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.
Sakai
Y
Y
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Québec, Canada.
Dobson
C
C
Diksic
M
M
Aubé
M
M
Hamel
E
E
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects; D049268:Positron-Emission Tomography; D012701:Serotonin / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology* / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014364:Tryptophan / Q000031:analogs & derivatives; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002250:Carbon Radioisotopes; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C028129:tryptophan methyl ester; D014364:Tryptophan; D018170:Sumatriptan