Migraine affects 16% of the world population and is one of the most disabling of all disorders. It is a complex brain disorder characterized primarily by recurrent headache attacks. The signaling molecule serotonin (5-hydroxytryptamine, 5-HT) has for decades been thought to play a central role in migraine pathophysiology. The most effective class of abortive migraine drugs, the triptans, act on 5-HT receptors. However, the migraine-specific actions of serotonin and the mechanisms of triptans are still unknown. In this project the investigators will use high-resolution positron emission tomography and specific radioligands to investigate the significance of serotonin in migraine. Two newly developed radioligands that are specific for the 5-HT1B and 5-HT4 receptor, respectively, will be applied. To investigate the level and distribution of serotonin in the migraine brain the investigators will compare the binding of these ligands in episodic migraine patients with healthy controls. In addition, the investigators will include chronic migraine patients to evaluate the relation between the level of serotonin in the brain and the frequency of migraine attacks. To investigate the changes in the serotonin level during a migraine attack and the effects of triptans on the central nervous system the investigators will repeat the scans using the 5-HT1B specific ligand during induced migraine attacks and following treatment with sumatriptan. The results from this study will shed light on the role of serotonin in the migraine brain and elucidate the migraine-specific action of triptans. This will improve our understanding of the migraine pathophysiology and, potentially, facilitate the development of more efficient treatment of migraine.

Inclusion Criteria, both groups:

• Written informed consent

Inclusion Criteria, episodic migraine patients:

• Migraine without aura according to the International Headache Society (IHS) 0-4 days per month
• The migraine is treatable with sumatriptan

Inclusion Criteria, chronic migraine patients: Fulfill IHS criteria for chronic migraine

Inclusion Criteria, healthy controls:

• Do not suffer from migraine according to IHS
• Do not have any first degree relatives with migraine

Exclusion Criteria:

• Tension type headache more than 5 days per month during the last year.
• Tension type headache on the experimental day.
• Any other primary headache disorder
• Migraine 48 hour before and after the experimental day (only episodic migraine patients)
• Use of antimigraine medication or pain-killer on the experimental day before PET
• Pregnant or breastfeeding women.
• Contraindications against MRI.
• History or clinical sign of cardio- or cerebrovascular disease.
• Untreated severe mental disorder or drug abuse.
• Other diseases or disorders interpreted, by the examining doctor, to interfere with participation in the study.
• Not accepting information about potential accidental findings during the experiment.

Migraine patients and healthy controls.