A migraine is not just a bad headache. It’s a cascade of electrical and chemical events that ripples through your brain, inflames the nerves surrounding it, and produces hours or even days of throbbing pain, nausea, and sensory overload. Migraine ranks as the third highest cause of disability worldwide, according to the World Health Organization, and it affects women far more often than men. Understanding what actually happens inside your brain during an attack helps explain why migraines feel so different from ordinary headaches and why they’re so difficult to shake.
The Brain’s Electrical Wave
The core event behind many migraines is something called cortical spreading depression: a slow wave of intense nerve cell firing followed by a prolonged shutdown. This wave rolls across the surface of the brain at roughly 2 to 5 millimeters per minute. During the wave, potassium ions flood out of neurons into the surrounding fluid, doubling in concentration, while calcium and chloride levels drop sharply. The local pH falls from a normal 7.3 to about 6.9, making the environment more acidic. Large amounts of the excitatory chemical glutamate pour out at the same time.
After this burst of activity, the affected brain tissue goes quiet. Normal electrical activity is suppressed for 5 to 10 minutes, and deeper signaling can take 15 to 30 minutes to recover. If this wave passes through the visual processing area at the back of the brain, you experience the shimmering lights, zigzag patterns, or blind spots known as aura. About one in four people with migraines get aura, and it typically builds over at least five minutes before fading within an hour.
How Pain Signals Ignite
The brain itself has no pain receptors, so the headache doesn’t come from the electrical wave directly. Instead, the chemicals released during that wave, including potassium, glutamate, and signaling molecules from nerve endings, drift toward the meninges, the protective layers wrapped around the brain. There, they activate pain-sensing nerve fibers belonging to the trigeminal nerve, the major sensory nerve of the head and face.
Once those fibers are triggered, they release a powerful signaling molecule called CGRP (calcitonin gene-related peptide). CGRP causes blood vessels in the meninges to widen and surrounding tissue to become inflamed. This neurogenic inflammation, which involves swelling, leaking blood vessels, and the activation of immune cells called mast cells, sustains and intensifies the pain signal. The trigeminal nerve relays all of this to the brainstem and higher brain centers, producing the characteristic one-sided, pulsating headache along with nausea and sensitivity to light, sound, and smell.
CGRP has become so central to scientists’ understanding of migraines that an entire class of medications now targets it. These drugs block CGRP or its receptor, and meta-analyses show they roughly double the odds of being pain-free two hours after a dose compared to a placebo. They’re not quite as fast-acting as triptans, the older standard treatment, but they offer an important alternative for people who can’t tolerate triptans or have cardiovascular conditions that rule them out.
The Four Phases of an Attack
A migraine isn’t a single moment. It unfolds in up to four distinct phases, though not everyone experiences all of them.
Prodrome
Hours or even days before the headache arrives, you may notice subtle warning signs: unusual fatigue, irritability, difficulty concentrating, neck stiffness, food cravings, frequent urination, or excessive yawning. These symptoms are strongly linked to the hypothalamus, a small region deep in the brain that regulates sleep, appetite, and mood. Brain imaging studies show the hypothalamus activating during this early phase. It releases signaling chemicals like orexin (which controls wakefulness and hunger) and dopamine, which likely explain the cravings and fatigue that many people recognize as their personal migraine warning.
Aura
If you experience aura, it typically appears next. Geometric patterns, flashing lights, or blind spots develop gradually over five or more minutes and usually resolve within an hour, though roughly 20% of people have aura lasting longer. Aura can also involve tingling in the hands or face, difficulty finding words, or, in rare forms, temporary weakness on one side of the body.
Headache
The headache phase lasts anywhere from several hours to three days. Pain is usually on one side, pulsating, and worsened by physical activity. Nausea, anxiety, insomnia, and extreme sensitivity to light, sound, and smell often accompany it. This is when the trigeminal inflammation is at its peak.
Postdrome
Even after the headache fades, many people feel drained, achy, dizzy, and mentally foggy. Sometimes called a “migraine hangover,” this phase varies in length but can linger for a day or more.
Why Some Brains Are More Vulnerable
Migraine tends to run in families, and genetics play a significant role in determining who gets them. In rare, severe forms of migraine with temporary paralysis (hemiplegic migraine), researchers have pinpointed mutations in three specific genes: CACNA1A, ATP1A2, and SCN1A. Each of these genes codes for ion channels or pumps that control how charged particles like calcium, sodium, and potassium move in and out of brain cells. When these channels malfunction, the result is a brain that is electrically hyperexcitable, quicker to fire and slower to calm down. This makes cortical spreading depression easier to trigger.
Other gene variants have been identified in more common forms of migraine. A mutation in the TRESK potassium channel gene, for instance, causes hyperexcitability in the trigeminal nerve cells themselves, lowering the threshold for pain signaling. The common thread across all these discoveries is that migraine-prone brains have a lower threshold for the kind of electrical disruption that sets an attack in motion. Environmental triggers like stress, poor sleep, skipped meals, or bright lights don’t cause migraines on their own. They push a genetically sensitive brain past a tipping point.
The Estrogen Connection
Migraine is roughly two to three times more common in women than men, and the primary reason is hormonal. Fluctuating estrogen levels directly affect the brain’s excitability in several ways. When estrogen rises, it increases calcium flow into trigeminal neurons, making them easier to activate. It also suppresses the brain’s main calming system (GABA-based inhibition) by uncoupling certain receptors from the channels that normally quiet nerve cells down. The net effect is a brain that’s primed for cortical spreading depression.
Estrogen withdrawal, the sharp drop that happens just before menstruation, creates its own problems. Falling estrogen pulls down serotonin levels, a chemical already found at lower baseline levels in people with migraines. This is why menstrual migraines are so common and predictable, often striking in the day or two before a period starts. The pattern also explains why migraines frequently change character during pregnancy (when estrogen stays high) and around menopause (when estrogen fluctuates erratically before declining for good).
What Keeps the Cycle Going
One reason migraines last so long is a process called sensitization. Once the trigeminal nerve fibers in the meninges have been firing for a while, they become increasingly responsive to stimuli that wouldn’t normally bother them. Blood vessel pulsing that you’d never feel under ordinary circumstances starts registering as throbbing pain. This peripheral sensitization can then spread centrally, meaning neurons in the brainstem and higher brain areas also become hypersensitive. That’s why, deep into a migraine, even light touch on the scalp or face can feel painful, and normal light or sound becomes unbearable.
This cascade, from electrical wave to chemical release to nerve inflammation to widespread sensitization, explains why treating a migraine early tends to work better than waiting. Once sensitization takes hold, the pain becomes self-reinforcing and harder to interrupt. It also explains why migraines are not just “in your head” in the dismissive sense. They involve measurable, structural changes in brain activity, blood flow, and nerve function that unfold over hours and take time to fully resolve.