Chapter 3, Episode 5: Migraine Pathophysiology


This content has been medically reviewed by Dr. Sarah Ahmad.

Migraine is a complex neurological disease that is estimated to affect approximately 1 billion people worldwide. Experts have not identified all of the changes that happen in the brain and body during a migraine attack but multiple factors are thought to be involved. 

People with migraine have brains that experience sensory overload quicker than those who don’t have migraine. The sensitive brain can be caused by genetics, hormones, traumatic brain injury, and more. While people without migraine disease are often unbothered by lights, smells, and sound, these factors can trigger an attack in people with migraine. Triggers differ from person to person but may include certain foods, barometric pressure changes, alcohol, and lack of sleep.  

The brain’s reaction to triggers can cause disruption in the hypothalamus, brainstem and limbic system which can lead to mood changes, food cravings, yawning and fatigue. These are the symptoms commonly noticed hours to days before head pain begins. This is often referred to as the ‘prodromal’ period.

About one third of all migraine attacks are accompanied by an aura. An aura is thought to occur because of a phenomenon known as cortical spreading depolarization, which is a wave of electrical activity passing over the outer layer of the brain known as the cortex. The aura usually occurs before the headache symptom of migraine starts or just as the headache begins.

As the wave spreads over different parts of the brain, a variety of symptoms can occur such as phantom smells, abnormal skin sensations such as pins and needles or numbness or visual disturbances like flashing or sparkling lights.

Cortical spreading depolarization causes changes in brain activity and blood vessels. In response, the trigeminal nerve  is activated and releases neurotransmitters and other substances that cause inflammation in the meninges.

Neuroinflammation can cause many migraine symptoms including head pain, nausea, vomiting, and skin sensitivity.

Experts believe that the thalamus has a key role in the way the nervous system processes pain signals as well as other sensory inputs like light, sound, and touch. Signals are processed by the thalamus and relayed to other brain areas involved in emotional regulation and cognition, which is why migraine can be associated with so many different neurological symptoms, such as changes in mood and thinking. The thalamus has many other roles, as one of the brain’s most complex structures.

There is still a lot to learn about why this complex neurological disorder occurs and what happens in the brain during an attack but research is bringing us more answers every day. 

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This video is sponsored in part by Amgen.



*The contents of this video are intended for general informational purposes only and does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. AMD does not recommend or endorse any treatment, products, or procedures mentioned. Reliance on any information provided by this content is solely at your own risk.