What Happens to Blood Vessels During a Migraine?

Blood vessels in and around the brain undergo real, measurable changes during a migraine attack, but the changes are more varied and less straightforward than the old “throbbing artery” explanation suggests. Some intracranial arteries widen modestly, the middle meningeal artery on the pain side swells in a way that correlates with where the headache is felt, and in people who experience aura, a brief wave of reduced blood flow sweeps across the cortex before the headache begins. Research over the past few decades has flipped the original understanding of these changes: most scientists now see vascular shifts as a downstream consequence of nervous-system activation rather than the root cause of the pain.

How the Vascular Theory Rose and Fell

For much of the twentieth century, doctors explained migraine as a blood-vessel problem. The logic was intuitive: the headache throbs in time with the pulse, vasodilating drugs can trigger attacks, and vasoconstrictors can stop them. Those observations pointed squarely at arteries as the culprits. Starting in the 1980s and 1990s, however, brain-imaging studies began to show that the picture was more complicated. Blood-flow changes did not always line up neatly with when and where the pain started, and some patients had full-blown migraines with minimal vascular change at all.¹

The shift accelerated as researchers learned that key molecules involved in migraine, particularly calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP), do far more than simply widen blood vessels. They also dial up pain signaling in neurons throughout the trigeminal system, the network of nerves that senses pain in the head and face. That finding pushed the field toward a “neurovascular” model in which the nervous system drives the attack and vascular changes tag along as a side effect.² The debate is not completely settled. CGRP-blocking antibodies that work mainly outside the brain have proven remarkably effective at preventing migraine, and some researchers argue this peripheral, largely vascular site of action deserves a second look.³

The Trigeminovascular System and How It Fires Up

The core machinery behind vascular changes during a migraine is the trigeminovascular system. Nerve fibers from the trigeminal nerve wrap densely around the blood vessels of the meninges, the membranes that cover the brain. When these fibers become activated, they release neuropeptides including CGRP and substance P directly onto the vessel walls. The result is neurogenic inflammation: blood vessels dilate, surrounding tissue swells with fluid, and the pain-sensing nerve endings in the area become sensitized so that even a normal arterial pulse can register as throbbing pain.⁴

CGRP is the molecule that has received the most attention. It is one of the most potent vasodilators in the body, and blood levels of CGRP rise during migraine attacks. But its role goes well beyond relaxing smooth muscle in artery walls. It sensitizes pain neurons, modulates immune cells, and influences how the brain processes sensory signals. This is why drugs that block CGRP can relieve migraine without causing dangerous blood-vessel constriction elsewhere.⁵ PACAP, a related peptide, shares several of CGRP’s abilities: both cause vasodilation, both trigger neurogenic inflammation, and both can provoke migraine-like attacks when infused into people. Yet they appear to act through independent signaling pathways, which is why blocking one does not always block the other.⁶

What Happens to Specific Arteries During an Attack

Imaging studies have tried to catch blood vessels in the act by scanning people during spontaneous or drug-induced migraine attacks. One landmark study used magnetic resonance angiography to compare artery size on migraine days versus non-migraine days. The intracranial arteries on the pain side, such as the middle cerebral artery and the internal carotid artery within the skull, showed dilation of roughly 11 to 13 percent during an attack. Extracranial arteries, including the superficial temporal artery, the one you can feel pulsing at your temple, showed no statistically significant dilation.⁷ This was a surprise, since the superficial temporal artery had long been assumed to be the source of the throbbing sensation.

A separate study using induced migraine focused specifically on the middle meningeal artery, the main blood supply to the dura mater. At the onset of pain, the middle meningeal artery on the pain side expanded significantly more than on the non-pain side, while other arteries dilated on both sides without any pain-side preference. The researchers concluded that middle meningeal artery dilation may serve as a marker for activation of dural pain sensors, pointing to the meninges as the site where headache pain actually originates.⁸ Together these studies suggest that the vascular changes during a migraine are selective: intracranial and meningeal arteries participate, while the scalp arteries people often blame play a smaller role than expected.

What Aura Does to Blood Flow

About a quarter to a third of people with migraine experience aura, typically visual disturbances like zigzag lines, blind spots, or shimmering arcs that develop over several minutes before the headache starts. The biological event underlying aura is cortical spreading depression, a slow wave of intense neuronal firing followed by a period of silence that rolls across the surface of the brain at roughly two to three millimeters per minute. As this wave passes, blood flow in the affected cortex drops and remains low for an extended period, a condition called oligemia. The factors driving this reduced blood flow are still being worked out but appear to involve local release of vasoconstricting molecules.⁹

So during aura, the vascular story runs in the opposite direction from the headache phase: blood vessels in the cortex constrict, and blood flow falls. This is not the same as a stroke (the blood flow reduction is modest and temporary), but it can produce genuine neurological symptoms. People sometimes lose parts of their visual field, feel tingling down one side of their body, or have difficulty finding words. Those symptoms pass as the wave of cortical spreading depression moves on.

Cortical spreading depression also has a recently discovered effect on the brain’s waste-clearance system. In animal experiments, a single wave rapidly and nearly completely closed the paravascular spaces around cortical arteries and veins, with recovery taking about thirty minutes. This impaired glymphatic flow, the process by which fluid moves through channels around blood vessels to flush waste products from brain tissue.¹⁰ Whether this temporary disruption contributes to the headache that follows, or has longer-term consequences in people with frequent aura, remains an open question.

Between Attacks, Blood Vessels Are Not Quite Normal Either

Most discussion of migraine and blood vessels focuses on what happens during an attack. But researchers have also found abnormalities in how blood vessels and neurons coordinate between attacks. Neurovascular coupling, the mechanism by which active brain regions receive increased blood flow, appears to be altered in people with migraine even during headache-free intervals. A brain-imaging study comparing migraine patients without aura to healthy controls found significant differences in the ratio of blood flow to local brain activity across several brain regions, and the degree of mismatch correlated with how severely headaches affected patients’ daily lives.¹¹

This is an area where the evidence gets complicated. Some research has also pointed to signs of endothelial dysfunction, meaning the inner lining of blood vessels does not regulate dilation and constriction as effectively. One study in young women with migraine found elevated markers of endothelial activation, including higher levels of von Willebrand factor (a clotting protein released by stressed endothelium) and lower levels of nitric oxide metabolites (a sign of impaired vessel relaxation), with the strongest changes in women who experienced aura.¹² A broader narrative review catalogued similar findings, including altered populations of circulating endothelial progenitor cells and elevated endothelial microparticles in migraine patients, particularly those with aura.¹³

However, not every study agrees. A prospective study comparing migraine patients, people with other headache disorders, and healthy controls found no significant differences in endothelial markers between any of the groups, and no differences between migraine attacks and headache-free intervals.¹⁴ The inconsistency may reflect differences in patient populations, how endothelial health was measured, or whether participants had aura. For now, endothelial dysfunction remains a plausible contributing factor in migraine rather than a proven one.

Mast Cells, Immunity, and Vessel Walls

Blood vessel walls are not just inert tubes. They are surrounded by immune cells, including mast cells, which sit in the tissue around meningeal arteries in particularly high numbers. When the trigeminal nerve releases neuropeptides like CGRP, substance P, and PACAP during a migraine, those molecules activate mast cells, prompting them to dump their contents: histamine, prostaglandins, cytokines, and other pro-inflammatory substances. These mediators further dilate blood vessels, increase the permeability of vessel walls so that fluid leaks into surrounding tissue, and sensitize nearby nerve endings.¹⁵ This creates a feedback loop: nerve activation inflames the tissue around vessels, and the resulting inflammation further excites the nerves. Breaking that loop is one of the goals of both acute and preventive migraine treatments.

How Migraine Drugs Act on Blood Vessels

The most widely used acute migraine medications, triptans, work partly by constricting blood vessels. They activate serotonin receptors (specifically the 5-HT1B type) on the smooth muscle of intracranial arteries, which tightens those vessels back down. But that is only one piece of their action. Triptans also block the release of neuropeptides from trigeminal nerve endings and suppress pain signaling in the brainstem, so their benefit does not come from vasoconstriction alone.¹⁶ The vasoconstrictor component, however, is the reason triptans carry warnings for people with heart disease or uncontrolled high blood pressure: the same receptors exist on coronary arteries.¹⁷

Newer preventive therapies take a different approach. CGRP-blocking antibodies and small-molecule CGRP antagonists (gepants) target the neuropeptide itself or its receptor, reducing the cascade of vasodilation, inflammation, and nerve sensitization without squeezing blood vessels tighter. Because CGRP has important vasodilating and organ-protective roles elsewhere in the body, there were initial concerns that blocking it long-term might cause cardiovascular problems. So far, clinical trials have shown a reassuring safety profile, possibly because other members of the CGRP peptide family and a second CGRP receptor compensate for the reduced activity.¹⁸

Migraine, Stroke, and Long-Term Vascular Risk

People with migraine, especially migraine with aura, face a modestly elevated risk of certain cardiovascular events, particularly ischemic stroke. This association has been confirmed across multiple large studies and is strong enough that it influences clinical decisions: combined estrogen-progestin contraceptives are generally avoided in women who have migraine with aura because the combination further raises stroke risk. A recent genomic analysis found that migraine with aura shares more genetic overlap with cardiovascular diseases than migraine without aura does, including a notably stronger correlation with ischemic stroke. Migraine without aura, by contrast, showed a stronger genetic connection to hypertension. Genetic liability to hypertension was itself associated with roughly a twofold increase in migraine risk.¹⁹

One piece of the puzzle may be small-vessel disease in the brain. Brain MRIs of migraine patients sometimes reveal tiny white matter lesions, bright spots that indicate areas of minor tissue damage. A single-center study found these lesions in about 36 percent of migraine patients, predominantly in the frontal lobes and clustered near the cortical surface. Age was the only strong predictor of whether they appeared.²⁰ These lesions are generally asymptomatic and do not seem to progress into cognitive problems in most people, but their presence underscores that migraine is not purely a pain disorder — it involves the brain’s vascular infrastructure in subtle ways.

There is even a genetic condition that links vascular disease and migraine directly. CADASIL is an inherited small-vessel disease of the brain, and migraine with aura is one of its earliest and most common symptoms. The ion-channel problems in CADASIL share features with those seen in familial hemiplegic migraine, a rare monogenic form of the disease.²¹ Studying these rare genetic variants has provided clues about how blood-vessel fragility and migraine susceptibility overlap at the molecular level.²²

Hormones and Cerebrovascular Reactivity

The fact that migraine is roughly three times more common in women than in men, and that attacks often cluster around menstruation, has prompted research into how hormones affect blood vessels in the brain. A study measuring cerebrovascular reactivity across the menstrual cycle in young healthy women found that changes in blood-flow velocity in the carotid and internal carotid arteries were significantly associated with fluctuations in ovarian hormones. The researchers noted an asymmetry, with the vasculature on the right side of the brain appearing more responsive to hormonal shifts.²³ Estrogen in particular modulates nitric oxide production in endothelial cells, and the drop in estrogen just before menstruation may leave blood vessels temporarily less able to regulate their tone. This hormonal influence on vessel reactivity likely explains at least part of the menstrual timing of many women’s migraines, though teasing apart hormonal, neural, and inflammatory contributions remains difficult.

Cardiac Shunts and Microemboli

One of the more unusual vascular connections in migraine involves patent foramen ovale (PFO), a small hole between the left and right atria of the heart that persists from fetal development. PFO is common in the general population, but it appears even more frequently in people with migraine with aura. The leading explanation is that a PFO allows tiny blood clots or other particles to bypass the lungs’ filtering system and reach the brain. Animal experiments have shown that microemboli in the cerebral circulation can trigger cortical spreading depression, the same phenomenon that produces aura.²⁴ Clinical trials of PFO closure for migraine prevention have produced mixed results: some patients improve dramatically, but the procedure has not been shown to reliably cure migraine across the board. The connection remains real enough to investigate but too inconsistent to recommend closure purely as a migraine treatment.