Migraines are caused by abnormal activation of pain-signaling nerves in and around the brain, combined with changes in blood flow and inflammation of brain tissue. Unlike a tension headache, a migraine involves a specific chain of neurological events that researchers have mapped in increasing detail over the past two decades. The process starts deep in the brainstem and involves a major nerve network called the trigeminal system, which is responsible for sensation in your face and head.
The Nerve System Behind Migraine Pain
The core of a migraine lies in something called the trigeminovascular system. This is a network of nerve fibers, mostly from the trigeminal nerve (the largest nerve in your head), that wraps around major blood vessels in your brain, the membrane covering your brain, and large drainage veins. When these fibers get activated, they release signaling chemicals directly into the walls of those blood vessels.
The most important of these chemicals is a protein called CGRP. When released from activated nerve endings, CGRP causes blood vessels inside and outside the skull to widen and triggers localized inflammation. This inflammation sensitizes surrounding nerve endings, which is why the throbbing pain of a migraine can worsen with each heartbeat, and why normal movements like bending over suddenly feel agonizing. Researchers confirmed CGRP’s central role by showing that simply infusing it into a person prone to migraines can provoke an attack. Blocking CGRP receptors is now a primary strategy in newer migraine treatments.
Other signaling molecules get released alongside CGRP, including substance P and nitric oxide. Together, they promote what scientists call neurogenic inflammation: swelling and irritation caused not by injury or infection, but by the nervous system itself. This is why migraines can produce such intense pain without any structural damage to the brain.
What Starts the Chain Reaction
Before the trigeminal system fires, something has to set it off. Brain imaging studies have identified several deep brain structures that show increased activity during and even before a migraine attack. These include the periaqueductal gray (a region in the midbrain involved in pain regulation), an area in the upper brainstem called the dorsal pons, and the hypothalamus, which controls sleep cycles, hunger, and hormone release.
In the period right before an attack, the brainstem’s built-in pain-filtering system appears to weaken. Normally, a pathway running from the midbrain down to the spinal trigeminal nucleus (where head and face pain signals arrive) dampens incoming pain signals, keeping you from feeling minor stimuli as painful. Research published in the Journal of Neuroscience found that in the hours before a migraine, the connection between these pain-modulating regions weakens, and the trigeminal nucleus becomes more responsive to painful stimuli. In other words, the brain’s pain volume knob gets turned up before the headache even starts.
This helps explain why many people experience warning signs hours or even a day before the pain hits: fatigue, mood changes, food cravings, neck stiffness, or increased sensitivity to light. These “prodrome” symptoms reflect the early involvement of the hypothalamus and brainstem before the full pain cascade begins.
How Migraine Aura Works
About one in four people with migraines experience aura, typically visual disturbances like shimmering zigzag lines, blind spots, or flashing lights that develop over 5 to 60 minutes before or during the headache. Aura is caused by a phenomenon called cortical spreading depression: a slow wave of intense nerve cell firing followed by a prolonged period of electrical silence that moves across the surface of the brain.
Functional MRI studies at Harvard captured this process in real time. The wave begins with a burst of neural activity in the visual cortex, causing local blood vessels to dilate. This initial surge corresponds to the bright, scintillating visual patterns people report. The wave then creeps across the brain’s surface at roughly 3.5 millimeters per minute, and in its wake, nerve cells go quiet and blood flow drops. The visual symptoms follow the same progression, mapping neatly onto the brain’s visual layout. If the wave reaches areas processing sensation or language, it can cause tingling, numbness, or temporary difficulty finding words.
Cortical spreading depression also appears to activate the trigeminal system directly, possibly by releasing potassium and other irritants into the space around nerve fibers. This is one pathway by which aura transitions into headache, though many people develop migraine pain without ever experiencing aura, suggesting the trigeminal system can be triggered through other routes.
Hormonal Factors
Migraines affect women roughly two to three times more often than men, a gap that opens at puberty and narrows after menopause. This pattern points strongly to the role of estrogen. A systematic review published in JAMA found that migraine attacks correlate with declining estrogen levels, particularly the sharp drop that occurs in the days before menstruation. It is not a specific low level of estrogen that triggers an attack. Rather, it is the withdrawal after a prolonged period of elevated estrogen that seems to lower the threshold for a migraine.
Progesterone levels, by contrast, do not appear to independently influence migraine timing. Estrogen affects several systems relevant to migraines, including serotonin signaling pathways and the excitability of brain circuits. This is why hormonal transitions like menstruation, pregnancy, and perimenopause can dramatically change how often someone gets migraines, and why hormonal contraceptives sometimes improve or worsen the pattern.
Common Triggers and Why They Matter
A migraine-prone brain sits closer to its activation threshold than a non-migraine brain. Triggers are the factors that push it over the edge. Stress is the single most commonly reported trigger. It likely works through the hypothalamus and stress hormones that increase neural excitability and alter pain processing. Notably, many people find that migraines strike not during peak stress but in the “letdown” period afterward, like the first day of a weekend or vacation.
Other well-established triggers include:
- Sleep disruptions. Both too little sleep and oversleeping can provoke attacks. Irregular sleep schedules are particularly problematic because they destabilize the hypothalamic circuits involved in migraine initiation.
- Skipped meals. Eating at irregular times or fasting lowers blood sugar and may alter brain energy metabolism in ways that trigger an episode.
- Alcohol. Wine is the most frequently cited culprit, though any alcoholic drink can be a trigger. Alcohol promotes blood vessel dilation and dehydration, both of which feed into the migraine cascade.
- Caffeine changes. Both excessive caffeine intake and sudden withdrawal can trigger attacks. Caffeine constricts blood vessels, so stopping abruptly causes rebound dilation.
- Sensory overload. Bright or flickering lights, loud sounds, and strong smells are common triggers and also make symptoms worse once an attack is underway.
- Weather changes. Shifts in barometric pressure, temperature swings, and seasonal transitions trigger migraines in a substantial number of people, though the exact mechanism is unclear.
- Certain foods. Aged cheeses, fermented or pickled foods, processed meats, and foods with certain preservatives are reported triggers. These foods contain compounds like tyramine and nitrates that may affect blood vessel tone or neurotransmitter levels.
- Medication overuse. Ironically, taking pain relievers too frequently (including migraine-specific ones) can cause rebound headaches that increase migraine frequency over time.
Triggers rarely act alone. A single glass of wine might not cause a migraine on its own, but combined with poor sleep, a skipped meal, and a stressful day, it may be enough to cross the threshold. This is why the same trigger does not reliably produce an attack every time, which can make identifying your personal triggers frustratingly inconsistent.
Genetics and Inherited Risk
Migraines run strongly in families. If one of your parents has migraines, your risk is roughly double that of the general population. If both parents are affected, the risk climbs higher. No single gene causes migraines. Instead, dozens of genetic variants each contribute a small amount to overall susceptibility by influencing ion channels in nerve cells, neurotransmitter metabolism, and the sensitivity of blood vessels to inflammatory signals.
What you inherit is not a guarantee of migraines but a lower threshold for triggering them. Your brain’s electrical and chemical environment is tuned in a way that makes the trigeminal cascade easier to set off. This is why two people can face the same stressors, sleep schedules, and dietary habits, and only one develops migraines.
Who Gets Migraines
Migraine is one of the most common neurological conditions worldwide. According to the World Health Organization, headache disorders collectively affect about 40% of the global population, with migraine being one of the most disabling subtypes. Migraines most often begin around puberty, peak in prevalence between ages 35 and 45, and generally become less frequent later in life, particularly in women after menopause. The strong female predominance during reproductive years reinforces the hormonal contribution to the disorder.
Despite its prevalence, migraine remains underdiagnosed. Many people assume their recurring headaches are just “bad headaches” and never receive a formal diagnosis. Understanding the biological mechanisms behind migraines can help reframe them not as something you should push through, but as a neurological condition with identifiable processes happening in your brain, processes that respond to targeted treatment.