A migraine attack begins in the brain, not in the blood vessels. For decades, doctors believed migraines were caused by blood vessels expanding and pressing on nerves, but the modern understanding points to a cascade of abnormal nerve activity that starts well before the pain hits. This cascade involves overexcitable brain cells, inflammatory signaling molecules, and a pain network centered on the trigeminal nerve, the largest sensory nerve in your head.
The Brain Starts Firing Before You Feel Pain
Hours or even a day before a migraine headache begins, a region deep in the brain called the hypothalamus becomes unusually active. Brain imaging studies have confirmed this activation during the “prodrome” phase, the early warning period when people notice food cravings, yawning, fatigue, or mood changes. The hypothalamus regulates sleep, hunger, body temperature, and hormone release, which explains why those premonitory symptoms feel so physical. This early brain activity is not a response to pain. It appears to be part of what initiates the attack itself.
If you experience aura (visual disturbances, tingling, or speech difficulties before the headache), what’s happening in your brain is a phenomenon called cortical spreading depression. A wave of intense nerve cell firing moves slowly across the outer surface of the brain, followed by a prolonged period where those nerve cells go quiet. Functional MRI studies have captured this in real time: first, a spike in blood flow and brain activity (starting in the visual processing area, which is why people see flickering lights or blind spots), then a drop in blood flow and suppressed activity that takes about 15 minutes to recover to 80% of normal levels. This wave of excitation and suppression spreads at roughly 3 to 5 millimeters per minute, matching the slow march of visual aura symptoms across your field of vision.
How the Pain Signal Builds
The headache phase involves a network called the trigeminovascular system. A web of mostly unmyelinated nerve fibers, originating from the trigeminal nerve’s ophthalmic branch and upper cervical nerve roots, wraps around the blood vessels of the brain, the large venous sinuses, and the protective membrane surrounding the brain (the dura). When these fibers become activated, they release inflammatory signaling molecules into the surrounding tissue.
The most important of these molecules is CGRP (calcitonin gene-related peptide). During a migraine attack, CGRP levels in the blood rise and fall in direct proportion to headache intensity. CGRP causes blood vessels to dilate and promotes inflammation around the nerve endings in the meninges, creating a feedback loop: inflamed tissue activates more nerve fibers, which release more CGRP, which drives more inflammation. This is why migraine pain tends to build and throb rather than arriving all at once. The nerve signals travel to a relay station in the brainstem, which then sends pain information upward to higher brain centers. Some of those same pathways connect to areas controlling nausea and vomiting, which is why those symptoms so often accompany the headache.
This process, called neurogenic inflammation, also explains why your scalp or face can feel tender during and after an attack. The inflammation sensitizes nerve endings so that normal sensations (touching your head, bending over, even your pulse) register as painful.
Why Some Brains Are Vulnerable
Migraine runs in families, and genetics play a significant role in determining whether your brain is prone to these attacks. The clearest genetic evidence comes from familial hemiplegic migraine, a rare and severe subtype where single gene mutations have been identified. These mutations affect ion channels and pumps that control how nerve cells fire and how chemical messengers like glutamate (the brain’s main excitatory signal) are cleared from the spaces between neurons.
One mutation causes calcium channels to open too easily, flooding nerve terminals with calcium and releasing excess glutamate. Another disables a pump responsible for clearing potassium and glutamate from the space between brain cells, leaving the brain in an overexcited state. A third affects sodium channels in a way that causes inhibitory neurons to fire excessively, which paradoxically raises potassium levels outside cells and primes the brain for cortical spreading depression. All of these mutations converge on the same problem: a brain that tips too easily into the runaway electrical activity that launches an attack.
For common migraine (the type most people have), the genetics are more complex. Large-scale studies have identified dozens of gene regions that each contribute a small amount of risk. Some of these involve genes related to blood vessel function, others to inflammation or brain signaling. A variant in the gene for an enzyme involved in folate metabolism has been linked to migraine with aura. Variants near genes that regulate blood vessel constriction have also been implicated. No single gene “causes” typical migraine, but the cumulative effect of many small genetic contributions creates a brain with a lower threshold for attacks.
Triggers That Push You Over the Threshold
Having a migraine-prone brain means you live closer to a threshold. Triggers are the factors that push you past it on any given day. The American Migraine Foundation identifies these as the most common:
- Stress is the single most frequently reported trigger, and the letdown period after stress (a weekend after a hard week, for example) can be just as potent.
- Irregular sleep is a powerful driver. Nearly half of all migraine attacks occur between 4:00 a.m. and 9:00 a.m., and both too little sleep and too much sleep can set off an episode.
- Hormonal changes affect roughly 60% of women with migraine. The drop in estrogen just before menstruation is the primary culprit (more on this below).
- Caffeine and alcohol work in opposite directions depending on the dose and timing. Caffeine withdrawal is a well-known trigger, and alcohol, particularly red wine, can provoke attacks in susceptible people.
- Weather changes, especially shifts in barometric pressure, humidity, or temperature, trigger attacks in many people.
- Certain foods including aged cheese, cured meats, chocolate, foods containing MSG or histamine, and artificial sweeteners like aspartame.
- Dehydration is an underappreciated trigger that is also one of the easiest to address.
- Bright or flickering light and strong smells can both initiate attacks, reflecting the heightened sensory sensitivity of the migraine brain.
- Medication overuse, particularly frequent use of pain relievers, can paradoxically increase attack frequency over time.
Triggers rarely act alone. A single glass of wine might not cause an attack on a well-rested day but could reliably trigger one when combined with poor sleep and stress. This stacking effect is why the same trigger doesn’t always produce the same result, which can make identifying your personal triggers frustratingly inconsistent.
The Estrogen Connection
Hormonal migraine deserves special attention because it affects so many women and follows a predictable pattern. The leading explanation centers on estrogen withdrawal: in the days before menstruation, estrogen levels drop sharply. Under normal conditions, estrogen helps regulate inflammatory gene activity in the trigeminal nerve system, essentially keeping a lid on the pain signaling pathway. When estrogen falls, that regulatory effect disappears. The brain’s compensatory mechanisms sometimes can’t adjust quickly enough to prevent an attack, particularly in a brain that’s already primed for migraine.
This explains why menstrual migraines tend to be more severe and harder to treat than attacks at other times in the cycle. It also explains why migraine patterns often shift dramatically during pregnancy (when estrogen stays high), perimenopause (when estrogen fluctuates wildly), and after menopause (when estrogen stabilizes at a low level, and many women see improvement).
Not a Vascular Problem
The old theory that migraines were caused by blood vessels dilating and constricting held sway for most of the 20th century. Harold Wolff’s experiments in the 1940s showed that migraine intensity tracked with pulsations in branches of the external carotid artery, and that reducing those pulsations reduced the pain. This seemed like clear evidence of a vascular cause.
Over the past two decades, that view has been largely overturned. Blood vessel changes do happen during migraine, but they appear to be a consequence of nerve activation rather than the root cause. Brain imaging shows that neural changes precede vascular ones, and effective migraine treatments work primarily on nerve signaling rather than blood vessel diameter. The current consensus treats migraine as a neurovascular disorder, one where abnormal nerve activity drives vascular changes, not the other way around. The throbbing quality of migraine pain, long attributed to pulsating arteries, is now understood to reflect sensitized pain pathways that amplify the normal sensation of your pulse rather than an actual problem with the vessels themselves.