Migraines happen because of a chain reaction in the nervous system: a wave of abnormal electrical activity spreads across the brain, triggering inflammation and pain signaling along a major nerve pathway that supplies the head and face. This isn’t just a bad headache. Migraine is the third leading cause of disability worldwide, affecting billions of people, and the process behind it involves genetics, brain chemistry, hormones, and energy production at the cellular level.
The Chain Reaction Inside Your Brain
The core event in a migraine is the activation of the trigeminal system, a network built around the trigeminal nerve, which is the largest nerve in your head. This nerve has branches that reach into the membranes surrounding your brain and the blood vessels that supply it. When the system fires, those nerve endings release signaling molecules that cause blood vessels to dilate and surrounding tissue to become inflamed. The result is intense, throbbing pain, typically on one side of the head.
The most important of these signaling molecules is called CGRP. Released from activated trigeminal nerve fibers, CGRP widens blood vessels inside and outside the skull and amplifies pain signals traveling to the brain. This molecule is so central to migraines that an entire class of newer treatments works by blocking it.
But the trigeminal system doesn’t fire on its own. Something upstream has to set it off, and that’s where the picture gets more complex.
What Triggers the Trigeminal System
Many migraines begin with a phenomenon called cortical spreading depression: a slow wave of intense electrical activity that rolls across the brain’s surface, followed by a prolonged period where those neurons go quiet. Functional MRI studies have captured this wave moving through the visual cortex at roughly 3.5 millimeters per minute. That speed matches the pace at which visual aura symptoms, like shimmering zigzag lines or blind spots, spread from the center of your vision outward over about 20 to 27 minutes.
Not everyone experiences aura. About one in four people with migraines do. But cortical spreading depression may still play a role in migraine attacks without aura, potentially occurring in brain regions that don’t produce noticeable visual or sensory symptoms. When this wave of electrical disruption reaches the meninges (the protective layers around the brain), it activates the trigeminal nerve endings there, kicking off the pain cascade.
The Early Warning Phase
Hours or even a day before the headache starts, many people notice subtle changes: food cravings, excessive yawning, mood shifts, fatigue, or neck stiffness. These premonitory symptoms point to the hypothalamus, a small structure deep in the brain that regulates sleep, appetite, mood, and body temperature. Brain imaging studies have shown increased activity in the front part of the hypothalamus during this early phase, well before any pain begins. This suggests the migraine process starts much earlier than the headache itself, with the hypothalamus acting as an early driver.
These warning signs are often mistaken for triggers. A person who craves chocolate before a migraine and then eats it may blame the chocolate, when in reality the craving was already part of the attack.
Why Some People Get Migraines and Others Don’t
Genetics play a significant role. Heritability is estimated at 38% for men and 48% for women, meaning roughly half the reason someone develops migraines can be traced to inherited factors. But familial factors account for less than 50% of all cases, so environment and individual biology matter just as much. Researchers have identified numerous genes involved, many related to ion channels (which control electrical signaling in neurons), serotonin receptors, and blood vessel function.
What genetics seem to do is set your threshold. People with migraine-prone brains have a nervous system that’s more excitable, more sensitive to disruption. The same amount of sleep deprivation, stress, or hormonal change that another person shrugs off can push a migraine brain past its tipping point.
Hormones and the Estrogen Connection
Women experience migraines roughly three times more often than men, and the reason is largely hormonal. Estrogen and progesterone influence pain-related chemicals in the brain, and steady estrogen levels tend to improve headaches. It’s the drops and fluctuations that cause problems. The natural decline in estrogen just before menstruation is a well-known trigger, which is why many women report migraines in the day or two leading up to their period or during it.
This pattern also explains why migraines often improve during pregnancy (when estrogen levels are consistently high) and can worsen during perimenopause (when hormone levels become erratic). For some women, migraines ease after menopause once hormone levels stabilize at a lower baseline.
Energy Problems at the Cellular Level
There’s growing evidence that the brains of people with migraines have trouble producing energy efficiently. Studies measuring brain chemistry in migraine patients found that magnesium levels and the energy released by cells were significantly reduced in the back of the brain compared to healthy controls. Specifically, free magnesium in the brains of migraine patients measured around 152 micromoles per liter, compared to 184 in people without migraines.
Magnesium is essential for stable mitochondrial function (mitochondria being the energy-producing structures inside every cell). When mitochondria underperform, magnesium levels drop further, creating a cycle of energy deficit. This cellular energy shortage may make the brain more vulnerable to the electrical disruptions that initiate attacks. It also helps explain why magnesium supplementation and compounds that support mitochondrial function have shown benefit for some migraine sufferers.
Common Triggers and Why They Work
Triggers don’t cause migraines on their own. They push an already-susceptible brain past its threshold. The most commonly reported triggers include:
- Stress and stress letdown: Both high-stress periods and the sudden relaxation after them (like the first day of a vacation) can provoke attacks.
- Sleep disruption: Too little sleep, too much sleep, or irregular sleep schedules all increase risk.
- Hormonal shifts: Menstruation, ovulation, and hormonal medications can trigger episodes in susceptible women.
- Sensory overload: Bright or flickering lights, strong smells, and loud noise are frequent culprits.
- Skipped meals and dehydration: Going too long without eating or drinking drops blood sugar and fluid levels, both of which lower the migraine threshold.
Most people with migraines have multiple triggers, and a single trigger rarely works alone. You might tolerate poor sleep on a normal day, but poor sleep combined with a skipped meal and a stressful meeting could be enough to set off an attack. This stacking effect is why migraines can seem unpredictable.
What a Migraine Attack Actually Looks Like
A full migraine unfolds in phases, though not everyone experiences all of them. The premonitory phase (yawning, cravings, fatigue) can start up to 48 hours before pain. If aura occurs, it typically lasts 5 to 60 minutes and involves reversible visual, sensory, or speech symptoms. The headache phase brings moderate to severe pain, usually pulsating and often one-sided, lasting anywhere from 4 to 72 hours if untreated. Physical activity like walking or climbing stairs makes it worse. Nausea, vomiting, and extreme sensitivity to light and sound are common during this phase.
After the pain fades, many people experience a postdrome or “migraine hangover,” with lingering fatigue, difficulty concentrating, and a washed-out feeling that can last another day. The entire cycle, from first warning sign to full recovery, can span several days for a single attack.