Migraine Pathophysiology

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Considerable debate has surrounded the cause and underlying pathology of migraine and several theories have been proposed.

The condition is generally thought to be of neurovascular origin, with research suggesting the pathological mechanism firstly involves the brain which, in turn, affects the blood vessels. Some researchers feel the key mechanism in the pathology is neurological while others believe the vasculature is at the centre of the pathology. The serotonin level is also thought to be an important factor.

Some of the theories regarding the pathophysiology of migraine include:

Depolarization theory

This theory suggests that a wave of electrical depolarization spreads across the cortex of the brain, depressing the function of certain brain areas as it moves over them. This leads to the release of inflammatory mediators that irritate the cranial nerve roots, particularly the trigeminal nerve. This nerve conducts the impulses that lead to sensation in most of the head and face. The depolarization theory is supported by positron emission tomography showing the spread of depolarization beginning around 24 hours before an attack. As the attack ensues, a large part of the brain becomes involved, which often includes the hypothalamus.

Vascular theory

Migraines typically occur when blood vessels in the head begin to contract and expand in an abnormal manner. The arteries in the back of the head have been shown to go into spasm, causing a reduced blood flow to the back part of the brain or the occipital lobe. This is thought to trigger aura that are followed by migraine.

Serotonin theory

Serotonin is a neurotransmitter or a chemical messenger in the brain that acts as a pain regulator and mood stabilizer and also plays a role in the dilation and constriction of blood vessels. Studies have shown that individuals who suffer form migraine have low serotonin levels, which is thought to dilate and swell the blood vessels and cause pain in the side of the head.


Hypothyroidism or low functioning thyroid glands are also considered to be one of the causes of migraine attacks. It has been suggested that the slowed metabolism and circulation seen in hypothyroidism leads to the retention of water and mucin which can cause blood vessels and tissues in the brain to swell and cause pain.


  1. http://www.nhs.uk/conditions/migraine/Pages/Introduction.aspx
  2. http://www.nice.org.uk/nicemedia/live/13901/60853/60853.pdf
  3. http://www.acponline.org/
  4. https://www.pfizer.ca/en
  5. https://healthy.kaiserpermanente.org/washington/front-door
  6. https://americanheadachesociety.org/
  7. http://uhs.berkeley.edu/home/healthtopics/pdf/triggers.pdf
  8. https://www.womenshealth.gov/

Further Reading

Last Updated: Jul 4, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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