Scientists have discovered a new way migraines occur – a breakthrough that could help them create new drugs for the debilitating disease.
More than one million Americans suffer from migraines that cause nausea, crippling pain and keep them from getting out of bed for hours.
One in four also suffer from extreme sensitivity to light, blurred vision and black spots, which makes it difficult for them to function.
Despite how common these migraines are, scientists understand little about what causes these attacks and many people have no medications that work.
But researchers have discovered that during a migraine with aura, different proteins are created that escape from the brain through microscopic openings and trigger intense pain.
According to Dr. Gottschalk, about 12 percent of Americans suffer from migraines. Of those, about a quarter have migraine with aura, which involves strange visual distortions.
Before some people feel a migraine, their vision is disrupted. This happens when a wave of signals passes through the brain, as in the illustrated diagram. With these signals, a fluid carrying migraine-causing proteins is diverted out of the brain and toward pain receptors.
For someone to feel pain, a migraine has to activate pain receptors outside the brain, something researchers have known for a long time.
How migraines travel from the brain to the rest of the body “has largely been a mystery,” said Dr. Jeffrey Iliff of Washington University School of Medicine and Dr. Andrew Russo of the University of Iowa, who were not involved in the study.
Dr. Iliff and Dr. Russo called the authors “pioneers” and said this could help us find new drugs for migraine sufferers. in a published response to the new study.
For people with moderate headaches, over-the-counter pain relievers like Advil and Tylenol are often helpful, but for migraine sufferers, these medications are often not enough.
There are FDA-approved medications for migraines, but they don’t work for many people, said the study authors from the University of Copenhagen and the University of Rochester Medical Center.
This is because migraines are not just intense headaches, they are something more serious than that. Dr. Christopher Gottschalkdirector of the Yale School of Medicine’s Headache and Facial Pain Center, who was not involved in the research.
Doctors will then prescribe medications such as triptans, which can treat the migraine once it starts, or antidepressants, anticonvulsants, or beta blockers, all of which should be able to prevent migraines.
But these drugs vary widely, and even when they work, they have unpleasant side effects, including nausea, insomnia, memory problems, weight gain and hair loss, Dr. Gottschalk said.
These side effects make these drugs “not a good option” for many migraine sufferers, he said. “Often, the price is too high for people.”
But to create drugs that treat migraines more effectively, doctors need to understand what causes them. Despite “thousands of years” of study, it’s still a topic of debate, the study authors said.
Researchers have long known that migraines do not act directly on the brain, since the brain itself does not have the ability to feel pain.
The brain is surrounded by multiple membranes that isolate it from the rest of the body and only allow the absolutely essential to pass through. Molecules find it difficult to pass through these layers, whether they are entering or leaving.
Researchers had no idea how these complicated migraines managed to bypass these barriers.
But they did know that in certain types of migraines, about an hour to five minutes before the pain starts, people start to have strange visual signs, such as blurred vision, blinding lights and black spots.
It turns out that when the aura begins, there is a rush of fluid and brain signals that move through the brain, propelling small molecules that trigger the migraine.
The study found that in mice, migraine-triggering molecules escape from the brain through this fluid, being pushed into a small space where the nerve that controls the face protrudes from the brain.
This was the first time anyone had identified this gap, Dr. Iliff and Dr. Russo wrote.
They believe these tiny particles, which are small proteins, could be targeted by new drugs to stop migraines.
“Although this work provides some of the most robust data to date on the role of the glymphatic system in migraine, there is much to discover,” Dr. Illif and Russo wrote.
Some of the molecules identified in this new study were already being investigated by pharmaceutical companies, they said.
In 2018, the FDA launched the first of these drugs, called calcitonin gene-related peptide inhibitors, after the particular protein they are designed to fight.
At the time, the American Migraine Foundation called this type of medication “the biggest development in migraine treatment and prevention in decades.” However, it still doesn’t solve migraine in all cases.
The other molecules the researchers found could therefore be key, said study author Dr. Martin Kaag Rasmussen, in enabling “the discovery of new drug targets that could benefit a large proportion of patients who do not respond to available therapies.”