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Abstract
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 α-[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.
Glossary
- 5-HT=
- serotonin; α-[11C]MTrp;
- 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.
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