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From Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada. Dr. Saki is currently with the Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan.
Address correspondence and reprint requests to Dr. Edith Hamel, Montreal Neurological Institute, 3801 University Street, Montréal, QC, Canada, H3A 2B4 edith.hamel{at}mcgill.ca.
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 
-[11C]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.
Abbreviations: 5-HT = serotonin; -[11C]MTrp = -[11C]methyl-l-tryptophan; Amy = amygdala; ANOVA = analysis of variance; B = bilateral pain; Cau = caudate; Cin = cingulate; Co = cortex; dBS = dorsal brainstem (including the periaqueductal gray matter and dorsal raphe nucleus); DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, third revised edition; Fro = frontal cortex; FWHM = full-width at half-maximum; Hipp = hippocampus; HSD = honest significant difference; IHS = International Headache Society; L = left hemicrania; MWA = migraine with aura; MWOA = migraine without aura; NS = not significant; Occ = occipital cortex; Par = inferior parietal cortex; Put = putamen; R = right hemicrania; R > L = mainly right hemicrania; RMANOVA = repeated-measures analysis of variance; ROI = region of interest; TAC = time–activity curve; Tha = thalamus; TSc1/d = time after Scan 1, in days; TS/m = time after sumatriptan injection, in minutes, at beginning of Scan 2; TO/h = time after migraine onset, in hours and minutes, at beginning of Scan 1.
Supplemental data at www.neurology.org.
*These authors contributed equally to this work.
Supported by a research grant (protocol no. SM40023, 518/410) from GlaxoSmithKline to E. Hamel, Principal Investigator.
Disclosure: GlaxoSmithKline participated in approving that the manuscript be submitted for publication. The authors report no conflicts of interest.
Received January 19, 2007. Accepted in final form September 17, 2007.
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