Objectives
To investigate brain 5-HT4-receptor binding with positron emission tomography (PET) as a proxy of serotonin (5-hydroxytryptamine, 5-HT) levels in migraine patients between attacks.

Methods
Brain 5-HT4-receptor binding, assessed with PET imaging of the specific 5-HT4-receptor radioligand, [11C]SB207145, is inversely related to long-term changes in brain 5-HT-levels. Eighteen migraine patients without aura (≥48 hours migraine free) and 16 age- and sex-matched controls underwent PET-scanning after injection of [11C]SB207145. Patients who reported a migraine attack ≤48 hours after the scan were excluded. The mean neocortical [11C]SB207145 binding potential (BPND) was calculated in a blinded manner.

Results
Fifteen patients (age 29.6 ± 10.2 years, 2 men) and 16 controls (28.9 ± 10.2 years, 3 men) completed the study. Migraine patients had significantly lower neocortical 5-HT4-receptor binding than controls (0.62 ± 0.09 vs. 0.68 ± 0.05, p = 0.024). We found no associations between 5-HT4-receptor binding and clinical migraine characteristics.

Conclusion
Migraine patients have lower neocortical 5-HT4-receptor binding than controls, which may reflect a chronic or at least episodically high brain 5-HT-level. Our finding is in apparent contrast with the longstanding hypothesis of migraine being a syndrome of chronic low brain 5-HT-levels. We were unable to demonstrate any associations with attack frequency or years with migraine. This suggests that high brain 5-HT-levels may be a trait of the migraine brain rather than a consequence of migraine attacks.