Migraine headaches are caused by abnormal activity in the nervous system, not simply by blood vessels expanding in the brain as scientists once believed. The process involves pain-signaling nerves becoming overly sensitive and releasing chemicals that create inflammation around the brain’s protective membranes. Over 1.16 billion people worldwide experienced migraines in 2021, with women affected nearly twice as often as men.
The Nervous System, Not Blood Vessels
For decades, the leading explanation was straightforward: blood vessels in and around the brain dilate, stretch surrounding tissues, and cause pain. This “vascular theory” made intuitive sense because migraines often produce a throbbing sensation that seems to pulse with your heartbeat. But recent imaging studies have largely dismantled it. One key study found no significant changes in blood vessels during spontaneous migraines in humans, leading researchers to conclude that vasodilation is not the direct cause.
The focus has shifted to what’s called the trigeminovascular system, a network of nerve fibers that wraps around the blood vessels of the brain’s outer membranes. During a migraine, small unmyelinated nerve fibers in this network release a signaling molecule called CGRP (calcitonin gene-related peptide). CGRP itself doesn’t directly cause pain. Instead, it triggers a cascade: it increases the production of nitric oxide, sensitizes neighboring nerve fibers, and amplifies pain signals being sent to the brainstem. This sensitization is why light touch, normal sounds, or even routine head movement can become excruciating during an attack.
CGRP also acts within a cluster of nerve cells called the trigeminal ganglion, where it interacts with surrounding support cells to keep the sensitization going. This creates a self-reinforcing loop. Pain signals from the peripheral nerves ramp up activity in second-order neurons deeper in the brainstem, which is why migraines can escalate and become harder to treat the longer they persist.
What Happens During Aura
About a quarter of people with migraines experience aura, visual disturbances like zigzag lines, blind spots, or flashing lights that typically appear before the headache begins. Aura is caused by a slow wave of electrical activity that sweeps across the surface of the brain, called cortical spreading depolarization. As this wave passes through brain tissue, it releases noxious chemicals from cortical cells. These chemicals accumulate in the surrounding tissue and cerebrospinal fluid until they reach levels high enough to trigger pain-sensing nerve fibers along the brain’s outer membrane.
This “buildup” model explains several things that previously puzzled researchers. The typical 0 to 20 minute gap between aura ending and headache starting reflects the time it takes for those chemicals to accumulate. It also explains why some people experience aura without a headache afterward: if the wave of electrical activity is small or brief, the chemical buildup may not reach the threshold needed to activate pain pathways. In some cases, headache can even start before a visible aura appears, because subclinical spreading activity may be building up chemicals before the wave reaches brain areas that produce noticeable visual symptoms.
Serotonin’s Role in Pain Modulation
Serotonin, a chemical messenger involved in mood, sleep, and pain regulation, plays a complex role in migraines. Different types of serotonin receptors appear to have opposing effects: some subtypes may help trigger migraines, while others help prevent them. The most clinically important receptors are the 5-HT1B and 5-HT1D types. When serotonin activates these receptors on trigeminal nerve endings, it suppresses the release of CGRP and other pain-promoting molecules. This is exactly how triptans, the most widely used class of migraine-specific medications, work. They mimic serotonin’s action at these receptors, essentially turning down the pain signal at its source.
Serotonin’s protective effect goes deeper than just blocking pain chemicals in the moment. Activation of 5-HT1 receptors actually suppresses the gene responsible for producing CGRP in the first place, reducing the amount available for release during future nerve activation. When serotonin levels drop or receptor function is impaired, this brake on CGRP production loosens, making the trigeminovascular system more reactive.
Genetics and Inherited Vulnerability
Migraines run in families, and the genetic component is substantial. The clearest genetic evidence comes from familial hemiplegic migraine, a rare subtype that causes temporary paralysis on one side of the body during attacks. Mutations in at least four genes have been identified: CACNA1A, ATP1A2, SCN1A, and PRRT2. The first three all code for proteins that transport charged particles (ions) across nerve cell membranes. When these proteins malfunction, the balance of ions inside and outside neurons is disrupted, which interferes with the normal release and reuptake of neurotransmitters.
These mutations follow an autosomal dominant inheritance pattern, meaning you only need one copy of the altered gene (from one parent) to be at risk. That said, not everyone who carries the mutation develops migraines, a phenomenon geneticists call reduced penetrance. For common migraines without the hemiplegic features, the genetics are more complex. Dozens of gene variants, each contributing a small amount of risk, likely combine with environmental and hormonal factors to determine who gets migraines and how severe they are.
Hormonal Triggers in Women
The stark gender gap in migraine prevalence, roughly 725 million women versus 433 million men globally, points directly to hormones. The estrogen withdrawal hypothesis is the best-supported explanation for menstrual migraine. Estrogen has a modulatory effect on pain processing within the trigeminovascular system. When estrogen levels are high, as they are in the first half of the menstrual cycle, pain sensitivity tends to decrease. When estrogen drops sharply in the days before menstruation, the trigeminal pain system becomes sensitized.
This pattern is consistent across the lifespan. Before puberty, boys and girls get migraines at roughly equal rates. The gender gap opens dramatically during adolescence, peaks during the reproductive years (prevalence is highest in the 30 to 44 age range), and narrows again after menopause. It’s not low estrogen itself that triggers attacks, but the rate of decline. This is why migraines often improve during pregnancy, when estrogen levels are consistently high, and why they can worsen during perimenopause, when estrogen levels fluctuate unpredictably.
Common Environmental Triggers
People with migraines have a nervous system that is inherently more reactive, and various environmental factors can push that system past its threshold. Changes in barometric pressure are among the most commonly reported triggers. The proposed mechanism is that shifts in atmospheric pressure alter the physical load on blood vessels, changing intracranial pressure dynamics enough to activate the trigeminovascular system. This is why many people with migraines report attacks before storms or during rapid altitude changes.
Other well-established triggers include sleep disruption (both too little and too much), skipped meals, dehydration, alcohol, strong sensory stimuli like bright lights or intense smells, and psychological stress. Notably, it’s often the transition out of stress rather than the stress itself that triggers an attack, which is why “weekend migraines” or “letdown headaches” are so common. These triggers don’t cause migraines on their own. They act on a nervous system that is already primed for overreaction, which is why the same trigger can provoke an attack one day and not another.
The Gut-Brain Connection
A growing body of research has found that people with migraines have a measurably different gut microbiome compared to people without them. Several studies report that migraine patients show higher levels of certain bacterial groups, including Bacteroidetes and Proteobacteria, while having reduced overall species diversity. In other words, the gut ecosystem in people with migraines tends to be less varied and compositionally distinct.
The exact mechanisms linking gut bacteria to migraine attacks remain unclear, but the clinical implications are already showing up in trials. Across multiple randomized controlled trials, probiotic and synbiotic treatments (combinations of beneficial bacteria and the fibers that feed them) significantly reduced migraine frequency, severity, duration, and painkiller use. This doesn’t mean gut bacteria “cause” migraines in a simple sense, but it suggests that gut-brain signaling pathways, likely involving inflammation and neurotransmitter production, play a meaningful role in how often and how intensely migraines occur.
Age and Population Patterns
Migraine is not evenly distributed across age groups. New cases peak between ages 10 and 14, meaning the teenage years are when migraines most commonly first appear. Prevalence and disability then climb steadily, peaking in the 40 to 44 age range before gradually declining. The single largest group of people living with migraine is in the 30 to 34 age bracket, with over 128 million cases worldwide, largely because this age group combines high prevalence with a large global population.
One striking trend is that adolescents under 20 are the fastest-growing group for new migraine diagnoses, with prevalence and disability increasing more rapidly than in any other age category. The reasons likely include a combination of genetic susceptibility being expressed earlier, rising screen time, sleep disruption, and possibly shifts in diet and gut health patterns among younger populations.