What was the journey that led to migraine becoming a 'disease that can be cured with medicine'?
For a long time, the cause of migraines was unknown and there was no established treatment, so they were previously considered mental illnesses or even excuses for people who didn't want to work. The scientific journal Nature has summarized how research on effective treatments and therapies for such migraines has progressed.
Migraine is more than a headache — a radical rethink offers hope to one billion people
Since ancient times, migraines have been associated with the image of an incurable affliction: in ancient Egypt, healers tied clay crocodiles to patients' heads to pray for recovery, and in the late 17th century, surgeons are said to have drilled holes in people's skulls to treat migraines.
Myths and prejudices persisted well into the 20th century, and in the 1990s, when Arne May, a neurologist at the University Medical Center Hamburg-Eppendorf in Germany, began studying migraines, they were often dismissed as a 'psychological problem.'
'At that time, no one believed migraine sufferers and people just didn't want to go to work, so my patients were being treated by psychologists and psychiatrists,' May recalls.
Although this prejudice against migraines gradually faded, the prevailing hypothesis remained that they were 'vascular headaches' caused by the dilation of blood vessels, and they were generally considered to be no different from ordinary headaches.
That all started to change when researchers like May scanned the brains of migraine sufferers and found that certain brain areas become active during a headache attack.
Once it was discovered that migraines were not just a normal headache, research into them progressed, and it gradually became clear that there is a premonitory period in which brain activity increases from a few hours to a few days before the attack, an attack period accompanied by an overwhelming headache, a recovery period when symptoms such as depression appear, and an intermittent period until the next attack.
In parallel with this, neuroscientists Lars Edvinsson of Lund University in Sweden and Peter Goadsby of King's College London, who were studying unrelated headaches, discovered that calcitonin gene-related peptide (CGRP) is involved in migraines.
Based on this discovery, the CGRP inhibitor 'Gepant' and several
'Migraine patients who receive Gepant are literally moved to tears as they remember what life was like when they were normal,' Goadsby said.
These impressive results might tempt you to think that CGRP is the long-mysterious cause of migraines, but there are other factors at play: some studies have found that only about one in five migraine sufferers respond to CGRP inhibitors, and even those who respond well to CGRP inhibitors may still have some symptoms.
Since the 2010s, brain scan studies have solidified the idea that the hypothalamus plays a central role in
Regarding this, May points out, 'There is no doubt that this disease is related to the limbic system, but within the limbic system, the hypothalamus is particularly important.'
The limbic system is the area of the brain that processes sensory information and regulates emotions. Studies that scanned the brains of migraine sufferers over a period of several weeks found that connections between the hypothalamus and different parts of the brain strengthen just before a migraine attack begins and weaken during the headache period.
Current research into migraine has introduced the “migraine threshold hypothesis,” which posits that migraine is caused by dysregulated brain activity due to environmental or physiological triggers.
The list of possible triggers is long: research has found that hormones, foods, and environmental chemicals can stimulate the release of CGRP, which can lead to headaches, but some migraine sufferers also blame a variety of other factors, including the weather, which are also being investigated.
'Part of the answer clearly lies in genetics,' says Lynne Griffiths, a geneticist at Queensland University of Technology in Brisbane, Australia.
The heritability of migraines is estimated to be between 35% and 60%, and studies of many genetic variants have enabled researchers to calculate a 'polygenic risk score' that predicts a person's likelihood of developing migraines.
Chia Chun Chan, a neurologist at the Mayo Clinic in Rochester, Minnesota, also has high hopes for AI. In a study published in October 2024, Chan and his colleagues showed that an algorithm could calculate an individual's BMI, family history, and the frequency and duration of attacks to predict the effectiveness of CGRP inhibitors for migraines with 80% accuracy.
Chang and his team are currently working on developing algorithms that can predict attacks based on sleep disorders, weather changes, sensitivity to light, and nausea, which they say could make it possible to take preventative measures or start treatment earlier before a migraine attack occurs.
Andrea West, who has suffered from migraines for 70 years thanks to the CGRP inhibitor Atogepant, approved in the UK in 2024, said, 'This is a wonderful drug. It has really changed my life.'
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