Migraine headaches result from abnormal activity in the brain’s pain-signaling network, not simply from blood vessel problems as once believed. The process involves a cascade of electrical and chemical events that amplify pain signals from the membranes surrounding the brain. Genetics account for 30 to 60 percent of a person’s susceptibility, which is why migraines tend to run in families.
How the Brain Generates Migraine Pain
The pain of a migraine originates in a network called the trigeminovascular system, a term describing the relationship between the trigeminal nerve (the largest nerve in your head), the membranes covering your brain, and the central nervous system. The trigeminal nerve has branches that wrap around blood vessels in these membranes. When those nerve fibers become activated, they release powerful signaling molecules that trigger inflammation and dilate blood vessels in the surrounding tissue.
The most important of these signaling molecules is calcitonin gene-related peptide, or CGRP. It’s a potent vasodilator, meaning it forces blood vessels to expand. Once released from nerve endings, CGRP sets off a chain reaction: blood vessels swell, surrounding tissue becomes inflamed, and nearby pain receptors become sensitized. Those sensitized receptors then release even more inflammatory molecules, creating a feedback loop that intensifies and sustains the headache. This process, called neurogenic inflammation, is now considered a central mechanism of migraine pain. It’s the reason newer migraine medications are designed specifically to block CGRP.
What Happens Before the Pain Starts
A migraine attack doesn’t begin with a headache. It begins hours or even a day earlier in deeper brain structures. Brain imaging studies show increased blood flow in the hypothalamus, a region that regulates sleep, hunger, mood, and sensory processing, during the earliest phase of an attack. The midbrain also activates during this premonitory stage. This is why many people experience fatigue, food cravings, neck stiffness, or unusual sensitivity to light and sound before the pain ever arrives. Those early symptoms aren’t random; they reflect the specific brain regions where the attack is gaining momentum.
About one in four people with migraine also experience aura, typically visual disturbances like shimmering lines, blind spots, or zigzag patterns. Aura is caused by a slow-moving wave of electrical activity that spreads across the surface of the brain at roughly 3.5 millimeters per minute. Neurons fire intensely, then go quiet for an extended period. This wave usually starts in the visual cortex at the back of the brain, which is why visual symptoms are the most common form of aura. The entire episode typically lasts 20 to 60 minutes and usually resolves before or as the headache begins.
Why Some People Get Migraines and Others Don’t
Migraine is substantially genetic. Twin studies estimate its heritability at 30 to 60 percent, with migraine that includes aura showing stronger genetic influence than migraine without. Most cases are polygenic, meaning dozens or hundreds of small genetic variations each contribute a small amount of risk. These variants affect genes involved in both nerve cell signaling and blood vessel function, which aligns with what we know about how migraines unfold in the brain.
Rare familial forms of migraine follow a more straightforward inheritance pattern. Familial hemiplegic migraine, for example, is caused by mutations in genes that control ion channels, the tiny gates that let charged particles flow in and out of nerve cells. When those gates malfunction, nerve cells become abnormally excitable. While most people don’t have these rare mutations, they illustrate a broader principle: the migraine brain is inherently more reactive to stimulation than a non-migraine brain.
The Role of Hormones
Estrogen is the strongest hormonal influence on migraine, and its withdrawal is more important than its absolute level. When estrogen drops sharply, as it does in the days just before menstruation, migraine risk spikes. This is why menstrual migraine is so predictable for many women, arriving in the same narrow window of each cycle.
The mechanism involves estrogen’s interaction with serotonin, a brain chemical that helps regulate pain perception. During the luteal phase (the second half of the menstrual cycle), nitric oxide levels rise while serotonin levels fall. This combination lowers the brain’s threshold for pain, making it easier for a migraine to take hold. The same estrogen-withdrawal pattern explains why migraines often worsen during perimenopause, when hormone levels fluctuate unpredictably, and frequently improve after menopause, when estrogen stabilizes at a consistently low level.
Common Triggers and How They Work
Triggers don’t cause migraine in the way a virus causes a cold. They lower the threshold for an attack in a brain that’s already predisposed to one. This distinction matters because it explains why the same trigger might provoke an attack one week and not the next: your threshold shifts depending on sleep, stress, hormonal status, and other variables.
Sensory triggers like bright light and strong smells act through specific neural pathways. Light signals from the retina converge in a region of the thalamus (a sensory relay station deep in the brain) with pain signals from the membranes covering the brain. This convergence means that in a migraine-prone brain, light doesn’t just feel unpleasant during an attack; it can actually intensify the pain signal itself. People with migraine show measurable cortical hyperexcitability to light even between attacks, meaning their brains are wired to over-respond to visual input.
Dietary triggers involve specific compounds. Tyramine, found in aged cheeses and fermented foods, causes blood vessels to dilate. Nitrates in processed meats like hot dogs and deli slices do the same. Beta-phenylethylamine in chocolate has also been implicated. However, food triggers are highly individual, and the American Migraine Foundation notes that the role of diet is often overstated. Skipping meals, dehydration, and alcohol (especially red wine) are more consistently reported triggers than any single food.
Other well-established triggers include:
- Sleep changes: both too little and too much sleep can provoke attacks, likely through effects on the hypothalamus
- Stress letdown: migraines often strike not during peak stress but in the hours or days after it subsides
- Weather changes: shifts in barometric pressure affect some people, though the mechanism isn’t fully understood
- Physical exertion: intense exercise can trigger attacks in some individuals, which is one reason the diagnostic criteria include “aggravation by routine physical activity”
Migraine vs. Other Headaches
The International Headache Society defines migraine without aura as a headache lasting 4 to 72 hours (2 to 72 hours in children) with at least two of these features: pain on one side of the head, a pulsating or throbbing quality, moderate to severe intensity, and worsening with ordinary physical activity like walking or climbing stairs. You also need at least one accompanying symptom: nausea, vomiting, or sensitivity to both light and sound. Five attacks meeting these criteria are required for a formal diagnosis.
This matters because tension-type headaches, the most common type, feel different. They produce a pressing or tightening sensation on both sides of the head, don’t throb, don’t worsen with movement, and rarely cause nausea or light sensitivity. If your headaches are one-sided, pulsating, and make you want to lie down in a dark room, that pattern points strongly toward migraine.
Why Sensitivity Lingers Between Attacks
People with migraine don’t have entirely normal brains between attacks. Studies consistently show that the migraine brain maintains a state of heightened sensory responsiveness even during pain-free periods. This cortical hyperexcitability means the brain overreacts to stimuli that wouldn’t bother someone without migraine. It’s part of why triggers accumulate: a poor night’s sleep alone might not start an attack, but combined with a skipped meal and bright fluorescent lighting, the brain’s already-low threshold gets crossed.
This baseline sensitivity also explains why migraine is best understood as a chronic neurological condition rather than a series of isolated headaches. The attacks are the most visible symptom, but the underlying brain differences are always present. Preventive treatments work by raising this threshold, making it harder for triggers to push the brain into an attack.