Migraines are caused by abnormal activation of pain-sensing nerves that wrap around blood vessels in the brain’s protective membranes. This isn’t a simple headache from muscle tension or dehydration. It’s a neurological event involving waves of electrical activity, inflammatory signaling molecules, and a pain system that becomes progressively more sensitive as an attack unfolds. The process has multiple stages, and different factors, from hormones to genetics to weather, can set it in motion.
How a Migraine Starts in the Brain
The pain of a migraine originates in a network called the trigeminovascular system. Pain-sensing nerve fibers from the trigeminal nerve, the largest nerve in your head, wrap around blood vessels in the meninges (the protective layers covering your brain). When these nerve fibers become activated, they release a signaling molecule called CGRP, which dilates blood vessels in the meninges and triggers local inflammation. That inflammation further sensitizes the nerve fibers, creating a feedback loop that intensifies pain.
CGRP is central enough to the process that an entire class of migraine medications was developed specifically to block it. When released, CGRP also activates immune cells called mast cells in the surrounding tissue, which dump out their own batch of inflammatory chemicals. This cascade is why migraine pain tends to build and worsen over time rather than hitting all at once. Once the nerve fibers become sensitized, even the normal pulsing of blood through arteries registers as pain, which is what produces the characteristic throbbing sensation.
The pain signals travel from the trigeminal nerve to a relay station in the brainstem, then up to the thalamus, a deep brain structure that processes sensory information. CGRP and its receptors are present in these relay areas too, which helps explain why migraines don’t just cause head pain. They amplify all sensory input, making light, sound, and even smell feel overwhelming.
The Electrical Wave Behind Aura
About one in four people with migraines experience aura: visual disturbances like zigzag lines, blind spots, or tingling that spreads across one side of the body. This is caused by a phenomenon called cortical spreading depression, a slow-moving wave of intense electrical activity that sweeps across the surface of the brain. The wave depolarizes (fires) nearly all the brain cells in its path for about a minute, then silences them for several minutes afterward.
As this wave rolls across the cortex, it forces neurons and surrounding cells to release a flood of molecules, including potassium, glutamate, and nitric oxide. These substances diffuse to the brain’s surface and activate the pain-sensing nerve fibers in the meninges, effectively linking the aura phase to the headache phase. You can think of it as an electrical storm that leaves inflammation in its wake. Not everyone with migraines has aura, which means this wave isn’t always the trigger. But when it does occur, it reliably kicks off the pain cascade.
What Happens Before the Pain Begins
Many people notice warning signs hours or even a day before a migraine hits: fatigue, food cravings, mood changes, excessive yawning, or difficulty concentrating. These premonitory symptoms appear to originate in the hypothalamus, a small structure deep in the brain that regulates sleep, appetite, mood, and hormonal cycles. Neuroimaging studies have captured increased hypothalamic activity during this pre-attack phase.
The hypothalamus produces neurotransmitters like dopamine and orexins that influence both arousal and pain processing. When its activity shifts, it can lower the threshold at which pain signals reach conscious awareness. This is why the prodrome phase isn’t just an early warning. It’s an active part of the attack, reflecting a brain that’s already changing its internal chemistry before any head pain appears.
The Role of Serotonin
People who get migraines tend to have lower baseline levels of serotonin, a neurotransmitter that, among many other roles, helps constrict blood vessels and modulate pain signals. When serotonin drops further, blood vessels lose some of that constricting influence. Nitric oxide, a potent vasodilator, goes relatively unopposed, which contributes to the vessel dilation and pain signaling that characterize a migraine.
This serotonin connection also helps explain why migraines are so closely linked to hormonal shifts. Estrogen influences serotonin metabolism, so when estrogen falls (as it does right before menstruation), serotonin levels drop along with it. The triptans, one of the most commonly used classes of migraine-stopping medications, work partly by mimicking serotonin’s effects on blood vessels and nerve signaling.
Hormonal Triggers and Menstrual Migraine
About 60% of women with migraines notice a connection to their menstrual cycle. The mechanism is straightforward: the sharp drop in estrogen that occurs in the days before a period lowers the pain threshold in the trigeminovascular system. Animal studies confirm this relationship directly. When estrogen is removed, pain sensitivity increases across multiple types of stimuli, and restoring estrogen reverses the effect.
Estrogen doesn’t just passively set the stage. It actively modulates pain processing in the brainstem relay stations where migraine signals are transmitted. During the second half of the menstrual cycle, as estrogen levels decline, the trigeminal pain pathway becomes measurably more sensitive. This is why menstrual migraines are often more severe and harder to treat than attacks at other times of the month. The same withdrawal mechanism explains why some women develop migraines during the placebo week of hormonal birth control or during the transition to menopause, when estrogen levels fluctuate unpredictably.
Genetics and Family Risk
Migraines run in families. If one of your parents has migraines, your risk is substantially higher than someone with no family history. The clearest genetic evidence comes from a rare subtype called familial hemiplegic migraine, where single gene mutations in ion channels and cell membrane pumps directly cause attacks. These mutations are inherited in a dominant pattern, meaning each child of an affected parent has a 50% chance of inheriting the variant.
Common migraines don’t follow such a clean genetic pattern. Instead, they involve dozens or possibly hundreds of gene variants, each contributing a small amount of susceptibility. Many of these variants affect how neurons manage electrical excitability, how blood vessels respond to signaling molecules, or how the brain processes sensory information. What you inherit isn’t the migraine itself but a nervous system that’s more reactive to triggers, one that sits closer to the threshold where a normal stimulus tips over into a full attack.
Common Triggers and Why They Work
People with migraines often identify specific triggers: certain foods, stress, poor sleep, bright lights, or weather changes. These aren’t causes in the way a virus causes a cold. They’re the final push that tips an already-susceptible brain past its threshold.
Weather is one of the more studied environmental triggers. In a year-long diary study of 28 migraine patients, 64% showed an association between weather changes and migraine onset. Specifically, attacks increased when barometric pressure dropped by more than 5 hectopascals around the day of the headache. The mechanism likely involves pressure changes affecting the sinuses or altering neuronal excitability, though the exact pathway isn’t fully established.
Dietary triggers vary widely between individuals. Aged cheeses, cured meats, red wine, and chocolate are frequently cited, largely because they contain compounds like tyramine that stimulate the release of stress hormones. Tyramine doesn’t appear to have a migraine-specific effect. Rather, it activates the same adrenaline-related pathways that other forms of physiological stress do, and in a susceptible brain, that’s enough. Skipping meals may be a more reliable dietary trigger than any specific food, likely because the resulting blood sugar drop and stress response lower the migraine threshold.
Sleep disruption works through similar mechanisms. Both too little and too much sleep can trigger attacks, probably by affecting hypothalamic regulation and serotonin metabolism. Stress is paradoxical: many people report migraines not during the stressful period itself but in the “letdown” phase afterward, like a weekend after a demanding work week. This pattern aligns with the idea that rapid shifts in brain chemistry, rather than any single state, are what push past the threshold.
Why Some People Get Migraines and Others Don’t
The fundamental difference between a migraine brain and a non-migraine brain is excitability. In people with migraines, the cortex is measurably more responsive to stimulation. Sensory inputs that a typical brain filters out, like flickering lights or strong smells, generate a larger electrical response. This hyperexcitability means the brain is always closer to the tipping point where normal nerve activity spills over into the spreading waves, inflammatory cascades, and pain signaling of a migraine.
This isn’t a flaw in one system. It’s a combination of genetic predisposition, hormonal environment, neurotransmitter balance, and the current state of the brain’s energy reserves. On a good day, with enough sleep, stable hormones, and low stress, the threshold stays high enough that no single trigger breaks through. On a bad day, when several factors converge, the same cup of coffee or change in weather that was fine yesterday becomes the last straw. That’s why migraines can feel so unpredictable even though the underlying biology follows consistent rules.