Migraines happen because of a cascade of electrical and chemical events in a brain that is wired to over-respond to sensory input. They are not simply “bad headaches.” A migraine is a neurological event with distinct phases, driven by genetic susceptibility, nerve activation, and inflammatory signaling that unfolds over hours or even days. Roughly 40% of the global population experiences headache disorders, with migraine disproportionately affecting women.
The Migraine Brain Is Different
People who get migraines have brains that process sensory information differently from people who don’t. Between attacks, migraine-prone brains fail to habituate normally to repeated stimuli. If you play the same sound over and over to someone without migraines, their brain’s response gradually dims. In a migraineur, that dimming doesn’t happen. The brain keeps responding at full volume. This isn’t the same as being more sensitive in a simple way. Researchers describe it as “over-responding” rather than being hyperexcitable, a subtle but important distinction.
Brain imaging reveals structural differences too. People with migraines tend to have reduced grey matter in areas involved in pain processing, including regions linked to emotion, attention, and body awareness. The part of the brain’s outer layer that maps sensation from the head and face is actually thicker than in people without migraines. The wiring between the brainstem’s pain-control center and other pain-relevant areas shows stronger connectivity, which may explain why pain signals amplify so readily during an attack. These differences also extend to how the brain handles light, sound, and smell, helping explain why everyday stimuli can become unbearable during and even between migraine episodes.
Genetics Set the Stage
Migraine runs in families, and twin studies put its heritability at 40 to 60%. The common forms of migraine have a complex genetic architecture. A large genome-wide study of over 102,000 migraine cases identified 123 regions of the genome linked to migraine risk, 86 of which were previously unknown. No single gene causes typical migraine. Instead, dozens of small genetic variations each nudge risk upward.
Rare inherited forms of migraine with temporary paralysis on one side of the body have been traced to three specific genes that all code for ion transporters, the channels that control how electrical signals move through nerve cells. While most people with migraine don’t carry those particular mutations, the finding pointed researchers toward the broader principle: migraine is fundamentally a disorder of how the brain manages electrical and chemical balance. Several of the newly identified risk regions contain genes targeted by newer migraine medications, reinforcing that the genetics are pointing in clinically meaningful directions.
What Happens Inside the Brain During an Attack
The signature event in many migraine attacks, particularly those with aura, is called cortical spreading depression. It’s a slow wave of intense nerve cell activation that rolls across the brain’s surface at 2 to 6 millimeters per minute, followed by a prolonged quiet period lasting 15 to 30 minutes where those neurons essentially shut down. If the wave crosses the visual processing area, you see the zigzag lines or blind spots characteristic of migraine aura. If it crosses sensory areas, you might feel tingling or numbness.
This wave does more than cause aura symptoms. As it moves, it forces nerve cells and surrounding support cells to release a flood of signaling molecules: potassium, glutamate, ATP, hydrogen ions, nitric oxide, and a peptide called CGRP. These molecules drift toward the brain’s surface, where they contact pain-sensing nerve endings wrapped around blood vessels in the protective membranes covering the brain. Those nerve endings become activated and then inflamed, triggering a chain reaction: blood vessels dilate, plasma leaks from vessels, and immune cells called mast cells release their contents. This is neurogenic inflammation, and it’s the bridge between the electrical event deep in the cortex and the pain you actually feel.
How the Pain Builds and Spreads
Once those pain-sensing nerve endings on the brain’s surface are activated, they send signals down the trigeminal nerve, the major sensory nerve of the head and face. Those signals land in a relay station in the brainstem, where second-order neurons pick them up and pass them toward higher brain centers.
Two types of sensitization make the pain progressively worse. First, the nerve endings themselves become hypersensitive to normal pulsing of blood vessels, which is why migraine pain often throbs in sync with your heartbeat. Second, the relay neurons in the brainstem become sensitized, which is why your scalp might hurt to touch, why wearing a ponytail becomes painful, or why your neck muscles feel tender. That spreading tenderness, called allodynia, is a sign that central sensitization has taken hold, and it’s one reason treating a migraine early tends to work better than waiting.
CGRP: The Key Chemical Messenger
Among all the molecules involved, CGRP (calcitonin gene-related peptide) has emerged as a central player. It is the most potent known peptide dilator of blood vessels in the brain and body. During a migraine attack, blood levels of CGRP rise measurably. Once released from trigeminal nerve endings, CGRP widens blood vessels, promotes leakage from vessel walls, and triggers mast cells to dump their inflammatory contents. This amplifies and sustains the neurogenic inflammation that drives migraine pain.
The importance of CGRP has been confirmed in a practical way: drugs that block CGRP or its receptor now form an entire class of migraine treatments, both for stopping attacks and preventing them. The genetic data supports this too, with several migraine risk genes mapping to targets in the CGRP pathway.
The Hypothalamus and Migraine Triggers
Many people notice that skipped meals, poor sleep, weather changes, or bright light can set off an attack. The hypothalamus, a small structure deep in the brain that regulates sleep, hunger, temperature, and hormonal cycles, appears to be the link between these triggers and the migraine cascade. Brain imaging shows the hypothalamus becomes unusually active the day before a migraine begins, well before any pain starts.
The current model is that when your body’s equilibrium is disrupted (you’re hungry, sleep-deprived, too hot, too cold), the hypothalamus lowers the threshold for the next migraine attack. It doesn’t directly cause the pain, but it makes the brain more vulnerable to tipping into one. Light is a particularly well-studied trigger. Specialized cells in the retina send signals directly to hypothalamic neurons, which then connect to both the parasympathetic and sympathetic nervous systems. These pathways help explain not only why bright light can trigger attacks but also why light worsens pain and nausea once an attack is underway.
Why Women Get More Migraines
Migraine is significantly more common in women than in men, a gap that widens after puberty and narrows after menopause. Hormonal fluctuations, particularly the drop in estrogen that occurs just before menstruation, are the most likely explanation. Many women report that their migraines cluster around their period, and this pattern is consistent enough that “menstrual migraine” is a recognized clinical category. The hormonal connection also explains why migraines often improve during pregnancy (when estrogen levels stay high) and can shift in frequency or severity with hormonal contraceptives or menopause.
The Four Phases of a Migraine
A migraine is not just a headache. It unfolds in up to four distinct phases, though not everyone experiences all of them.
The prodrome begins hours to days before pain starts. Common symptoms include neck stiffness, fatigue, sensitivity to light and sound, food cravings, mood changes, and frequent yawning. This phase appears to be driven largely by hypothalamic activity and is increasingly recognized as the true start of the attack, not just a warning sign.
The aura phase, when it occurs, typically lasts 5 to 60 minutes and involves fully reversible neurological symptoms. Visual disturbances (flashing lights, zigzag lines, blind spots) are most common, but some people experience tingling, numbness, difficulty speaking, or even temporary weakness. Aura is the direct result of cortical spreading depression moving across the brain.
The headache phase lasts 4 to 72 hours if untreated. The pain is typically on one side, pulsating, moderate to severe, and worsened by routine physical activity like walking or climbing stairs. Nausea, vomiting, and extreme sensitivity to light and sound are hallmarks. Not all migraines include severe head pain, though. Some people experience all the other neurological symptoms with only mild or no headache.
The postdrome can persist up to 48 hours after the headache resolves. People describe difficulty concentrating, fatigue, and lingering neck stiffness. Brainstem activation appears to persist during this phase, which explains why many people feel “off” even after the pain is gone. Understanding that this recovery phase is a real, physiological part of the attack, not just tiredness, can help you plan accordingly and avoid pushing through too quickly.