What is the real cause of migraine?

Our understanding of migraine is beginning to change, changing the concepts of what is a symptom and what causes it, and which part of the brain is the key to developing effective treatments.

What really causes a migraine?

Our understanding of migraine disorders is beginning to change, changing ideas about what the symptom is and what the trigger is, and which part of the brain is key to developing effective treatments.

About twice a week, the left side of my head starts to feel like there is a small space between my brain and my skull.When I bend over, the area fills with a dull ache.The pain went like a knife behind my eyeballs and down my jaw.Sometimes if I look, it burns and fades into the back of my mind.At other times, he would bang and shake, as if he were knocking on the door asking to come out.

The longer I let the pain go before taking my medicine, the longer it will take to subside and the more likely it will return as soon as the pill wears off.It's a migraine.

Over 1.2 billion people around the world can relate to some version of my experience.This neurological disorder is the second most common cause of disability in the world.Yet despite its common and debilitating effects, migraine remains largely a mystery.

There are many unanswered questions about what migraine is, why it occurs, and what can be done to eliminate this condition from patients' lives.

"I would say that it is probably among the most poorly understood of the neurological system of diseases or disorders in general," says Gregory Dussor, head of behavioral and brain sciences at the University of Texas at Dallas in the US.

Now researchers are beginning to unravel what triggers a migraine and have even recently been able to see it unfold in real time as electrical signals in a patient's brain.By studying genes, blood vessels, and the molecular cocktail in patients' heads, scientists are getting closer to understanding why migraines occur, how to treat them, and why it's not just an annoying headache, but a chronic experience for the whole body.

Why studying migraine is so difficult

At the beginning of the 18-19th century, migraine was generally a female passion: one of the intelligent, charming and beautiful women with "migraine personality".While three-quarters of migraine sufferers are women, the stigma that has lasted for centuries has made migraine research back and means it has chronic lack of funding.

"People think of it as a mental disorder," said Teshame Monteth, head of the department at the University of Miami Health System in the US.Even today, very few universities have strong centers for migraine research, and investment in this problem remains low compared to other areas of neurological conditions.

Experts no longer use the word "migraine" - as if headache is a condition.Instead, they now urge everyone to use the term migraine disorder instead, referring to a "migraine attack" as a flare-up of an underlying disease, which causes a variety of symptoms, including headaches.Episodic migraine is when the patient has fewer than fifteen headaches per month.Chronic migraines are when they are more frequent.

Still, the psychological, physical and financial burden of migraines is very real, Monteith said.Migraines are most common during the most productive years of a person's life, from their 20s to their mid-50s, when migraine sufferers are more likely to quit their jobs, become unemployed, or retire early.Migraines cost the national economy £12 billion ($17 billion) each year.

One of the challenges of studying migraine is the breadth of symptoms.

Like most people affected by migraines, I am a woman of childbearing age.Attacks are a major part of my life when I get my period.The headaches usually hit my left side and are worse with movement.It is preceded by a strong sensitivity to smell and sometimes my left shoulder and arm are frozen.

However, other patients experience symptoms such as nausea and vomiting, dizziness, abdominal pain, and increased sensitivity to light and sound.More than half of patients experience extreme fatigue, while some experience special food cravings.Others yawn excessively in the early stages.

"The whole migraine attack is a very complicated thing," says Dussor."It's not just pain. It's a whole series of events that happen long before the headache starts."

The triggers thought to trigger attacks are also varied: lack of sleep and fasting trigger my headaches, but other patients indicate that chocolate, aged cheese, coffee or a lack of white wine can trigger them.Stress seems to be associated with migraines in most patients, and interestingly, the spread of stress as well – which is why weekend attacks are classic.

Triggers vs Symptoms

Although scientists studying migraines have long been baffled by the wide range of different triggers, now a growing body of research suggests that many of these triggers may simply be early symptoms.

In fact, the patient may be consuming certain foods unknowingly at the beginning of an attack: chocolate or cheese, for example.This means it's easy to associate the food as a trigger for the attack, but the attack may have already started, says Debbie Hay, a professor of medicine and toxicology at the University of Otago in Dunedin, New Zealand.

Personally, I've always wondered if perfume is responsible for giving me migraine attacks.However, I wear perfume every day and I find that I only notice enough of the smell to try to blame it on my attacks on the days I actually wear the perfume.When I'm not having a migraine attack, I tend not to focus too much on what I'm smelling.

“Well, that's a classic example, and the reason is probably not that,” said Peter Goadsby, a professor of neuroscience at King's College London in the United Kingdom.

Goadsby analyzed the brain patterns of migraine patients who feel that light is the cause of their attacks and compared it with patients who do not usually blame light for the onset of their pain.Only the older ones had more activity in the part of the brain responsible for vision before the migraine, indicating that at that time they had the ability to be more sensitive to light than their peers."There's no question, something is going on in biology," Godsby says.

However, research into what the underlying biological mechanisms are has been going on for a long time.

Genetic origin of migraine

Twin studies show that there is a strong genetic component and that if your parents or grandparents have had migraines, you are statistically more likely to inherit the neurological condition as well.Inherited genes appear to play a role in about 30 to 60 percent of migraine sufferers, and the rest are influenced by other cumulative external factors such as life history, environment and behavior, says Dale Nyholt, a geneticist at the Queensland University of Technology in Australia.

Nyholt is examining thousands of people to find specific genes running amok, but the search is "more complicated than we'd ideally hope," he says.In 2022, he went through the genes of 100,000 migraine sufferers, and compared them with 770,000 people who don't have migraines.

He identified 123 "danger snips" — small differences in the human DNA code — that were linked to migraines.Now he's running another trial with 300,000 migraine sufferers, hoping to find out more.He believes "there are probably thousands".

In Nyholt's research, some genetic markers associated with migraine appear to be closely related to depression and diabetes, as well as to different structures in the brain.Nyholt suspects that there are "constellations" where the same genetic material can manifest as different conditions in the real world because of how they affect the brain.I don't know yet.)

Blood vs brain

Due to the occurrence of many headaches, one of the people who are suspected of having a migraine is used as a blood vessel that opens the brain and allows blood to flow in. But the researchers could not find a correlation between blood flow and migraine."It's just not as simple as 'blood vessels do X,'" Dussor said.

That doesn't mean blood vessels have nothing to do with migraines: Many of the risk genes Nyholt found in his genetic testing of migraine origin are genes that help regulate veins. Blood vessels dilate abnormally during an attack, and in fact, medications can be used to constrict them and help relieve migraines. So, while they are certainly involved in migraine attacks, they may not be the cause. Their effect on migraines maymay be due to other hidden factors, such as the abnormal release of pain-causing molecules in the walls of the veins or other signals sent from the veins to the brain, Dussault said. Or their dilation may simply be a symptom and not a cause of migraines.

"Migraine sits in the middle of what people call neurology and psychiatry," Goodsby says."Scientists at his school are making the connection between migraines and conditions like seizures, epilepsy or stroke. "The process that really relates to the central nervous system is the unraveling of its parts," Goodsby says, from the building blocks of brain cells to its structure and how electricity flows through neurons.

Creating brain waves

The main theory for scientists studying the brain's role in migraines is that an attack is a slow, abnormal electrical wave that spreads through the brain's cortex, known as cortical spreading depression.These waves suppress brain activity and cause nearby pain-relieving nerves to fire, sound the alarm, and cause inflammation.Michael Moskowitz, a professor of neurology at Harvard Medical School in Cambridge, Massachusetts, US, says the spreading cortical waves of depression essentially "throw all kinds of bad molecules into the brain".

But why does this fake wave start?And where does it spread?And how does this electrical wave lead to so many symptoms?This is still difficult to determine.In March 2025, scientists captured the wave in real time while monitoring the brain of a 32-year-old patient in preparation for surgery.The wave was picked up by 95 electrodes inserted into his skull.It spread from his visual cortex — which explains why some people are sensitive to light and see auras, Moskowitz says — and then into the brain for another 80 minutes.

This article is one of two parts focusing specifically on migraine disease.Stay tuned for the latest treatment options in part two on Friday, February 6th.

The various ways of the waves will help explain some people who have a head and some people are a headaches, place to the naked header than a waves.to the brain and prefer to detailed food.

Another study involving a single patient also suggested that a small area in the brain, called the hypothalamus, was surprisingly activated a full day before a migraine.After all, the hypothalamus is also involved in the stress response and sleep cycle, which is a common trigger of migraines.But a large study is needed to understand its role.

But importantly, not the visual cortex nor the hypothamalus is the place of migraine pain.Headaches were felt in the nerve fibers of the Meninges - the brain's thick, gelatinous, triple-layered ouves called the trigeminal ganglia, moving the trigeminal ganglia, scalp and eyes.That's why I feel my migraine attacks behind the eye sockets and up to the jaw.

So some scientists believe that this dark layer around the brain may hold the key to understanding migraines.

Enter the meninges

The meninges are flooded with immune cells whose job it is to protect the brain, and when they're excited, they release molecules that cause inflammation that can affect neurons on the other side of the meninges.Dussor and others hypothesized that an overreaction of these immune cells could lead to migraines.It can explain why migraine attacks in people seem to be more common with the statistics of allergic rhinitis and hay fever and the anecdotes that occur during the allergy season, such as allergens such as pollen in immune cells that can be regulated.

There are other features that may be an important link between the brain's environmental stimuli and what happens in the brain.Along this membrane are structures that can detect changes in acidity that may be caused by physiological abnormalities, inflammation surrounding the brain, or spurious electrical waves that reduce brain activity.When they detect that the meninges are acidified, they send electrical signals that stimulate the pain fibers involved in migraine attacks.

Other parts of the meninges respond similarly to heat and cold.This may explain why some patients relieve their headaches with ice packs or heating pads.

Hormonal fluctuations are often considered the culprit.Many patients report migraine attacks at the beginning of their menstrual cycle, and research has shown that a family of molecules known as prostaglandins can have a dramatic effect on the dilation of blood vessels in the brain.

Migraine Molecule Cocktail

All these different factors can interact."I think at the end of the day it's probably a common entity, but there are multiple pathways of migration," said Amina Pradhan, director of the Center for Clinical Medicine at Washington University in St. Louis. "There are many ways to treat migraine, and each has a cocktail."

However, the search for a standard, objective molecular biomarker of what makes a brain a migraine brain is far from over, and one of the most important breakthroughs in recent years has come from the search for one such molecule.Researchers have identified an unusually high level of a type of neuromodulator called calcitonin gene-related peptides, or CGRPs.These small proteins act as dimeric switches that increase or decrease neuronal activity and sensitivity.Goadsby and his team's research shows that their levels are higher during a migraine attack, but they also appear to be higher in people who experience migraines even when they don't have an attack.

This realization has led to the creation of new drugs on the market that target CGRP to eliminate or prevent the threat.This is a medical advance that has already relieved many patients of pain where other methods had failed.In another study conducted in October 2025, which included more than 570 patients taking CGRP for one year, 70% had a 75% reduction in the frequency of migraine attacks, and about 23% experienced complete resolution of their migraines.