Migraines are caused by abnormal electrical and chemical activity in the brain that triggers inflammation and pain signaling along a major nerve system in your head. Unlike a tension headache, a migraine isn’t simply muscle tightness or stress. It’s a neurological event with deep roots in genetics, brain chemistry, hormones, and environmental triggers, often working together.
Genetics Set the Stage
Common forms of migraine have an estimated heritability of 40 to 60 percent, meaning your genes account for roughly half of your overall risk. A landmark genome-wide study of over 102,000 migraine cases identified 123 specific locations in the genome linked to migraine susceptibility. Some of these genetic variants are specific to migraine with aura (the type that causes visual disturbances before the headache), while others are linked only to migraine without aura.
This genetic foundation helps explain why migraines run in families. If one or both of your parents get migraines, your chances of developing them rise significantly. Your genes influence how excitable your brain cells are, how your blood vessels respond to chemical signals, and how efficiently your brain clears inflammatory molecules. None of these genes cause migraines on their own, but they make your brain more reactive to the triggers described below.
What Happens Inside Your Brain During an Attack
The core event in many migraines is a phenomenon called cortical spreading depression: a slow-moving wave of intense electrical activity that rolls across the surface of your brain. Neurons fire rapidly, then go quiet, region by region. This wave is what produces the visual aura some people experience, such as shimmering lines, blind spots, or zigzag patterns that expand over 20 to 30 minutes.
But the wave does more than cause visual symptoms. As it moves across the brain, it triggers inflammation around the blood vessels in the protective membranes (meninges) surrounding your brain. This inflammation activates a network called the trigeminovascular system, which is essentially the brain’s main pain highway. Nerve fibers running along those blood vessels release powerful signaling molecules, including one called CGRP, that dilate blood vessels and sensitize pain receptors in the meninges.
Once those peripheral pain fibers become sensitized, they fire more easily and send amplified signals deeper into the brainstem and up to the thalamus, the brain’s relay center for pain. This cascade of sensitization, from the surface of the brain down into deeper structures, is why migraine pain often starts mild and builds, and why your head can become so sensitive that even normal movements or light touch feel painful. The same brain generating the headache is also the organ processing the pain signals, creating a feedback loop that sustains the attack.
The Role of CGRP
CGRP (calcitonin gene-related peptide) deserves special attention because it’s central to migraine pain and the target of newer migraine medications. This molecule is released from nerve fibers that run along blood vessels in the meninges. Once released, CGRP triggers a chain reaction: it causes blood vessels to widen, prompts immune cells called mast cells to release substances that further sensitize nearby nerves, and creates a feedback loop where pain fibers keep activating each other.
CGRP doesn’t just act at the surface. About half the neurons in the trigeminal ganglion, the cluster of nerve cells that relays pain signals from your head and face, contain CGRP. When small pain-sensing fibers release it there, it binds to receptors on neighboring nerve cells and supporting glial cells, amplifying the pain signal before it even reaches the brainstem. This is why medications that block CGRP or its receptor have proven effective at both preventing and stopping migraine attacks.
Hormonal Triggers
Roughly three times as many women as men experience migraines, and hormonal fluctuations are a major reason. The most well-supported explanation is the estrogen withdrawal hypothesis: migraines tend to strike when estrogen levels drop sharply after being elevated for a sustained period. This happens most predictably just before or during menstruation, when estrogen falls rapidly after the luteal phase of the menstrual cycle.
Research suggests a specific threshold matters. Migraines are more likely when estradiol (the main form of estrogen) drops below about 45 to 50 pg/mL after a period of higher levels. It’s not just the low level itself that triggers an attack; it’s the magnitude of the decline. This is why migraines often change across a woman’s life. They may worsen during perimenopause, when estrogen swings become more dramatic, and improve after menopause, when levels stabilize at a consistently low point. Both estrogen drops and sharp rises can precipitate attacks in people with a history of menstrual migraine, suggesting that the brain’s sensitivity to hormonal change, not just low estrogen, is the underlying issue.
Dietary and Chemical Triggers
Certain foods and additives can trigger migraines, though the mechanisms vary. Nitrates, found in processed meats like hot dogs and deli meats, are among the best-studied dietary triggers. Your body converts nitrates into nitric oxide, a molecule that dilates blood vessels. Nitrate-triggered headaches come in two forms: a mild, immediate headache within an hour from the blood vessel dilation itself, and a more severe delayed headache three to six hours later that closely resembles a migraine. The delayed version appears to involve the same CGRP release and nerve sensitization that drive other migraine attacks.
Interestingly, a large study from the American Gut Project found that people with migraines had higher levels of bacteria in their mouths that convert nitrates into their active forms. This suggests that your individual gut and oral microbiome may influence how strongly you react to nitrate-containing foods. Alcohol (especially red wine), aged cheeses, fermented foods, and caffeine withdrawal are other commonly reported dietary triggers, though individual sensitivity varies widely. Keeping a food diary for a few weeks is the most reliable way to identify your personal triggers.
Weather and Barometric Pressure
If you feel like your migraines come with the weather, you’re not imagining it. A study tracking migraine patients against daily atmospheric pressure readings found that attacks occurred most frequently when barometric pressure dropped 6 to 10 hPa below the standard pressure of 1013 hPa. About a quarter of patients in the study developed a migraine when pressure fell into this range. This corresponds to the kind of pressure drop you’d see with an approaching storm front or rapid weather change, not a dramatic hurricane-level shift.
The exact mechanism isn’t fully understood, but changes in external pressure may affect the pressure within your sinuses and the fluid-filled spaces around your brain, potentially altering blood vessel tone and triggering the trigeminovascular cascade in people whose brains are already primed for it.
Sleep Disruption and Stress
Poor sleep is one of the most consistent migraine triggers, and the connection runs through inflammation. Sleep deprivation activates the brain’s immune cells (microglia), which then release inflammatory molecules like IL-6 and TNF-alpha. These same molecules increase the excitability of neurons, essentially lowering the threshold for the spreading electrical wave that kicks off a migraine. Animal studies show that even a few days of sleep loss can disrupt the blood-brain barrier and trigger a sustained low-grade inflammatory state in the brain.
Your brain’s immune cells naturally follow a circadian rhythm, ramping up and down their activity throughout the day. When your sleep schedule is irregular, whether from shift work, jet lag, or simply inconsistent bedtimes, this rhythm gets disrupted, and the inflammatory baseline rises. Stress operates through a similar pathway. Chronic stress elevates cortisol and activates glial cells, creating the same kind of heightened brain excitability that makes a migraine more likely to ignite. Many people notice that migraines strike not during the most stressful period itself but during the “letdown” phase afterward, such as the first day of a weekend or vacation, when cortisol levels shift abruptly.
Why Triggers Stack Up
One of the most frustrating things about migraines is that a trigger that causes an attack one week may not cause one the next. This is because migraines typically require multiple factors to stack up at the same time. Your genetic sensitivity sets a baseline threshold. Hormonal shifts, poor sleep, a skipped meal, a weather change, or stress each push you closer to that threshold. On a day when only one factor is present, you may be fine. On a day when three or four converge, an attack breaks through.
This “threshold model” explains why migraines can feel unpredictable even when the underlying biology is consistent. It also means that managing migraines is rarely about eliminating a single trigger. Keeping sleep regular, managing stress, staying hydrated, eating consistently, and identifying your personal dietary triggers all work together to keep you further from that threshold on any given day.