This study aims to investigate whether the functional alterations in the brain of individuals with migraine appear before the peripheral vascular changes. This will be investigated using functional and structural neuroimaging in individuals with spontaneous menstually-related migraine.

Spontaneous migraine attacks are unpredictable and therefore been logistically arduous to investigate in neuroimaging studies. Menstrually-related migraine provides an opportunity to study spontaneous attacks in a controlled imaging setup. The present project aims to investigate women with menstrually-related migraine using daily functional magnetic resonance imaging (MRI) scans 2-3 days before the onset of the menstrual bleeding and until (and including) the headache phase of migraine or up to five consecutive days. A control-group of women without migraine will also be recruited and undergo the same MRI scan protocol.

Inclusion Criteria:

For women with migraine

- Episodic menstrually-related migraine without aura > 12 months according to the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria

For women with migraine and healthy women

• 18-40 years of age
• Weight 50-100 kg
• Regular menstruation

Exclusion Criteria:

For women with migraine

• Other primary headache disorders than migraine, except infrequent episodic tension-type headache according to the ICHD-3 criteria

• Secondary headache disorders

• Headache on the first scan day or 48 hours before the first scan

• Absence of the menstruation for the past 12 months

• Daily intake of medication of any kind except oral contraceptives

• Ingestion of any type of medication later than 4 times the plasma half-life of the substance in question (on the day of the scan), except for oral contraceptives

• Intake of coffee, tea or alcohol 12 hours prior to scan days

• Fertile women not using safe contraception. Fertile women are defined as women without hysterectomy and < 2 years postmenopausal women. Safe contraception includes the intrauterine device, oral contraceptive pills, surgical sterilization of the woman, depot progestogen or condoms

• Change of hormonal contraceptives for the past 3 months

• Perimenstrual syndrome

• Pregnant or breastfeeding women

• Information or clinical signs of:

  • Hypertension (systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg)
  • Low blood pressure (systolic blood pressure < 100 mm Hg and/or diastolic blood pressure < 50 mm Hg)

• Cardiovascular diseases of any kind, including cerebrovascular disease

• Diabetes

• Unregulated mental illness or substance abuse

• Illnesses of any kind deemed incompatible by the examining physician for participation in the study

• Contraindications to MRI (including metal in the body or claustrophobia)

• Do not want to be informed about unexpected pathological findings on the MRI

For healthy women

• History of any primary headache except infrequent episodic tension-type headache according to the ICHD-3 criteria

• First degree family history of primary headache disorders except infrequent episodic tension-type headache according to the ICHD-3 criteria (max five days/month)

• Secondary headache disorders

• Headache during the menstrual period from 2 days before to 2 days after the first menstrual bleeding day

• Headache on the first scan day or 48 hours before the first scan

• Absence of the menstruation for the past 12 months

• Daily intake of medication of any kind except oral contraceptives

• Ingestion of any type of medication later than 4 times the plasma half-life of the substance in question (on the day of the scan), except for oral contraceptives

• Intake of coffee, tea or alcohol 12 hours prior to scan days

• Fertile women not using safe contraception. Fertile women are defined as women without hysterectomy and < 2 years postmenopausal women. Safe contraception includes the intrauterine device, oral contraceptive pills, surgical sterilization of the woman, depot progestogen or condoms

• Change of hormonal contraceptives for the past 3 months

• Pregnant or breastfeeding women

• Perimenstrual syndrome

• Information or clinical signs of:

  • Hypertension (systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg)
  • Low blood pressure (systolic blood pressure <100 mm Hg and/or diastolic blood pressure < 50 mm Hg) Investigation of functional brain features in women with migraine

• Cardiovascular diseases of any kind, including cerebrovascular disease.

• Diabetes

• Unregulated mental illness or substance abuse

• Illnesses of any kind deemed incompatible by the examining physician for participation in the study

• Contraindications to MRI (including metal in the body or claustrophobia)

• Do not want to be informed about unexpected pathological findings on the MRI

Women with menstrually-related migraine and women with no history of migraine. All participants have regular menstruation and 18-40 years old.