What’s Really Happening During a Migraine?
Understanding the Biology, Genetics, and Brain Science Behind Migraines
Migraines are far more than just “headaches.” Millions of people suffer from these debilitating episodes, but many don’t know the underlying biological causes.
In a revealing discussion, Dr. Elizabeth Yarnell, ND, interviewed Dr. Amelia Scott Barrett, MD, about the biology, genetics, and cellular mechanisms of migraines. They explain why migraines happen, and more importantly, how understanding the science can guide prevention and treatment.
What Is a Migraine? More Than a Headache
Many people assume a migraine is simply severe head pain, often on one side. But biologically, migraines are complex neurological events involving multiple systems in the brain.
Dr. Yarnell asks:
“I remember my childhood, my mother would always… excuse herself to lie down in a dark room because she had a migraine. And she would always tell me that a migraine is when you have pain just on one side of your head. But you’re saying that that’s not necessarily the definition of a migraine?”
Dr. Barrett explains:
“One-sided pain is part of the diagnostic criteria, but it doesn’t fully define a migraine. Migraines involve a very specific set of events in the brain that differ from a typical headache.”
How Migraines Differ from Regular Headaches
| Feature | Migraine | Tension/Regular Headache |
|---|---|---|
| Pain Location | Often one side but can vary | Usually a band around the head |
| Duration | Hours to 3 days | Minutes to a few hours |
| Associated Symptoms | Nausea, vomiting, aura, light/sound sensitivity | Rarely associated symptoms |
| Underlying Mechanism | Trigeminal nerve activation, cortical spreading depression, vascular changes | Muscle tension, stress |
The Biological Cascade of a Migraine
Dr. Barrett breaks down the step-by-step events occurring in the brain. The first step in the process is “cortical spreading depression,” which is a wave of abnormal electrical activity across the brain. This triggers the trigeminal nerve, which then dilates blood vessels and releases inflammatory chemicals (including CGRP).
“Between these events, people experience typical migraine symptoms—sometimes aura, sometimes not—followed by severe one-sided throbbing headaches often associated with nausea or vomiting,” Dr. Barrett explains.
Understanding Migraine Aura
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Aura is a neurological phenomenon unique to migraines that occurs during cortical spreading depression.
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Symptoms may include:
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Jagged or flashing lights in a zigzag pattern on top of what you’re looking at, typically off to one side
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Blind spots or visual distortions
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Difficulty focusing or speaking
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“Aura is a very migraine-specific phenomenon and is linked to a unique set of genes,” Dr. Barrett notes.
Not all migraines include aura, but when it occurs, it’s a key diagnostic feature.
Genetics: The New Frontier in Migraine Research
Dr. Yarnell asks about genetics:
“So that’s a great segue. Let’s go into the biology underneath and what you’ve been doing with genetics…”
Dr. Barrett explains that genetics provides a roadmap to Recovery, which is different for everybody because the underlying causes of migraine are different from one person to the next.
Landmark Genetic Study
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2023 study: DNA from 100,000 people with migraines was compared to 700,000 without.
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Examined:
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22,000 genes per person
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4–5 million SNPs (single nucleotide polymorphisms)
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“If you think of a gene as a house, a SNP is just a different picture of the house. And if you think of a neighborhood as a biological system in the body, then you can see how many different genes work together to accomplish a function in the body,” Dr. Barrett explains. “This analogy helps us understand how modern genetic testing reveals how well biological systems are functioning.”
Four Key Biological Systems Linked to Migraines
Dr. Barrett identifies four systems strongly associated with migraine risk:
1. Inflammation
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Chronic or excessive inflammation can trigger migraine events.
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Genetic variations may affect how efficiently your body resolves inflammation.
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Inflammatory genes are often targets for migraine research and therapy.
2. Brain Chemistry (Neurotransmitters)
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Serotonin and other neurotransmitters play a central role.
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Variations can affect:
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Neurotransmitter production and breakdown
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How migraines respond to medication, which makes it easier to find meds that work for you
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3. Energy Production (Mitochondria)
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Brain cells require energy to function properly.
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Mitochondrial inefficiency can make the brain more susceptible to triggers.
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Supporting mitochondrial health may reduce migraine frequency and severity.
4. Vascular Function (Blood Flow Regulation)
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Blood vessel constriction/dilation is genetically influenced.
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Explains why:
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Hormonal changes often trigger migraines
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Some people develop vascular lesions visible on MRIs
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Hormones affect migraines through blood vessels, not direct hormone genes.
“That is part of why some people get high blood pressure and some people don’t,” Dr. Barrett notes.
MRI Findings and Migraine
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Most MRIs for migraine come back normal.
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Some show white matter lesions or microvascular changes, which may indicate subtle brain changes from chronic migraines. Most doctors dismiss these white matter lesions, but Dr. Barrett disagrees with this approach and recommends that you figure out why they are happening through further testing and treat those underlying problems to prevent further damage.
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Understanding genetics can help prevent further brain tissue changes.
“It’s all about prevention—how do we keep our brains as healthy as we can?” Dr. Barrett emphasizes.
Modern Genetic Testing vs. Ancestry Tests
Dr. Yarnell clarifies:
“Just so we can be super clear, we’re not talking about the genetic tests that say, ‘my ancestors are from Europe or Africa.’”
Dr. Barrett confirms:
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This testing focuses on health-related genes, not ancestry.
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It looks at:
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Inflammation
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Brain chemistry
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Mitochondrial function
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Vascular regulation
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“This is leaps and bounds ahead of ancestry testing and gives you actionable health information.”
How to Use Genetic Insights for Migraine Prevention
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Identify your genetic profile
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Tools like theheadachequiz.com can help pinpoint your migraine type.
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Target interventions
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Support inflammation pathways
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Optimize brain chemistry
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Enhance mitochondrial function
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Support vascular health
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Personalize lifestyle strategies
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Sleep, diet, stress management, and targeted supplementation can be guided by genetics.
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“We have a road map to recovery now,” Dr. Barrett says.
“It tells you how to support your body in accomplishing its proper function.”
Key Takeaways
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Migraines are complex neurological events, not just headaches.
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Cortical spreading depression triggers migraine symptoms.
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Aura is specific to migraines and genetically linked.
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Genetics reveals four major systems involved:
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Inflammation
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Brain chemistry (neurotransmitters like serotonin)
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Energy production (mitochondrial function)
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Vascular function (blood vessel regulation)
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Hormones trigger migraines indirectly through vascular changes.
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Modern genetic testing can guide personalized prevention and treatment strategies.
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Prevention is key: understanding your biology can protect brain health and reduce migraine frequency.
Where to Learn More
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Visit theheadachequiz.com to explore genetic headache testing.
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Start tracking triggers, symptoms, and response to lifestyle changes.
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Discuss findings with a healthcare provider for personalized migraine management.
“This is not information you will hear from regular doctors, and it’s far beyond what’s taught in medical school,” Dr. Barrett notes.
Migraines are complex, but understanding the underlying biology and genetics provides hope for prevention, personalized treatment, and better quality of life.