IntroductionSerotonin (5-HT) plays a role in migraine pathophysiology, but whether brain 5-HT is involved in the conversion from episodic to chronic migraine is unknown. Here, we investigated brain 5-HT levels, as indexed by 5-HT₄receptor binding, in chronic migraine patients and evaluated whether these were associated with migraine frequency.MethodsSixteen chronic migraine patients underwent a dynamic PET scan after injection of [¹¹C]SB207145, a specific 5-HT₄receptor radioligand. Data from 15 episodic migraine patients and 16 controls were included for comparison. Quantification of 5-HT₄receptor binding was used as a proxy for brain 5-HT levels, since 5-HT₄receptor binding is inversely related to brain 5-HT levels.ResultsChronic migraine patients had 9.1% (95% CI: [−17%; −1.0%]) lower 5-HT₄receptor binding compared to controls ( p = 0.039). There was no difference in 5-HT₄receptor binding between chronic and episodic migraine patients ( p = 0.48) and no association between number of monthly migraine days and 5-HT₄receptor binding (slope estimate 0.003, 95% CI: [−0.004; 0.715], p = 0.39).ConclusionThe finding of low 5-HT₄receptor binding suggests that cerebral levels of 5-HT are elevated in chronic migraine patients. This is in line with observations made in patients with episodic migraine. Elevated brain 5-HT levels may thus be an inherent trait of the migraine brain rather than a risk factor for conversion from episodic to chronic migraine.