If you are living with migraine you know how debilitating it can be. You’ve probably spent more days—or even weeks—than you can count lying in bed with the curtains drawn, waiting for the pain and other symptoms like light sensitivity and dizziness to go away. That’s because migraine is no ordinary headache—it’s a neurological disease that can severely affect your quality of life. Approximately 12% of adults in the U.S. have migraine (almost 40 million people), and it’s the sixth most disabling disease worldwide, according to the Cleveland Clinic.
Yet research to understand what causes migraine and what may treat it has been severely lacking, most likely due to stigma and limited awareness of the disease as well as insufficient funding. “If you look at diseases with similar levels of burden, they’re getting $200-plus million dollars from the National Institutes of Health whereas migraine only gets $20 to $25 million,” Amaal Starling, MD, a board-certified neurologist at the Mayo Clinic, tells SELF.
The good news is that funding for migraine research is increasing, slowly but surely, and new discoveries are being made every year. Here’s the state of migraine research right now, including which breakthroughs are coming down the pipeline.
Migraine is a complex disorder and its exact cause still isn’t fully understood. “The way I look at it is migraine is like an old puzzle where we have half the pieces and, therefore, we haven’t been able to put the puzzle together,” Stephen Silberstein, MD, board-certified neurologist and director of the Headache Center at Jefferson University Hospitals, tells SELF.
What experts do know is that migraine is a genetically inherited neurological disease that causes specific nerves in blood vessels to release substances that send pain signals to the brain, according to the Cleveland Clinic. Unfortunately, experts still don’t know why your nerves do that—but whatever the cause, it’s hereditary.
“More than 200 genetic mutations have been found to be involved in migraine vulnerability, and every person has a different combination of those,” Dr. Starling says. “I dream of the day when I can draw blood or take a saliva sample and it tells me the exact physiology of a person’s migraine so I can tailor treatment to them individually.” Until then, people with migraine have dozens of treatments to try, with new drugs and medical devices getting approved by the FDA each year. Ahead, the most exciting new migraine treatments to look out for.
In recent years the focus of migraine research has been on inhibiting the release of substances that send pain signals to the brain. “Researchers have been trying to peel apart, layer by layer, which chemicals are released and how to attack them one by one,” Jessica Ailani, MD, a board-certified neurologist at Medstar’s Georgetown University Hospital, tells SELF.
According to Dr. Ailani, there are many neuropeptides (chemical messengers in nerve cells) involved in migraine, but most recently researchers have focused on two: calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP). Research on CGRP is more advanced: In the last five years, several drugs that block CGRP receptors (known as CGRP antagonists) have been approved by the FDA, some of which are taken orally when a migraine strikes and some of which are self-injected monthly or quarterly to prevent migraine attacks from happening in the first place.
“PACAP is the next molecule that’s closest to nearing the finish line in clinical trials,” Dr. Ailani says. “It’s the next big thing we have our eye on.” Danish researchers have found that the neuropeptide PACAP-38 is a key player in migraine pathophysiology: A clinical trial showed that an infusion of PACAP-38 increases plasma levels of the neuropeptide and leads to migraine attacks.1 In a small study published in Brain, when the neuropeptide PACAP-38 was injected into people–12 with a history of migraine and 12 without–the majority of people experienced a migraine attack.2
Now drug companies are trying to create antibodies that specifically target PACAP receptors. A 2020 clinical trial tested a drug that targets one receptor called PAC1.3 It unfortunately didn’t improve migraine compared to the placebo. Researchers suggest a number of explanations, including that the concentration of the drug wasn’t high enough to have an effect, or that perhaps a different PAC receptor needs to be targeted instead of or in addition to PAC1. The good news, according to Dr. Silberstein, is that trials like this teach us more and more about the chemistry of migraine, bringing us closer to finding answers.
Once an effective PACAP inhibitor is found, people with migraine will have yet another drug to add to their arsenal of migraine treatments. “There are different pathways for migraine,” Dr. Silberstein notes. “One pathway is CGRP; another is PACAP. When we get a good PACAP drug, I suspect that nonresponders to the CGRP drug will respond to PACAP drugs.”
Another promising area of research is the study of how oxytocin (the “love hormone”) may play a role in inhibiting migraine. In 2017, Stanford researchers showed that when given as a nasal spray, oxytocin can significantly decrease migraine pain.4 More research is needed but so far the data has been positive, Dr. Ailani notes.
The thing about targeted migraine medications is that they often cause unpleasant side effects, like tingling or prickling of the skin, dizziness, dry mouth, and nausea, among others. And if you’re pregnant or have a health condition like coronary artery disease, you may not be able to take certain migraine drugs. In these instances, non-drug treatment options are crucial—and fortunately more and more are becoming available.
“An exciting area in the field of migraine is the development of wearable devices that can treat and prevent migraine,” Dr. Silberstein says. In the last five years, the FDA has approved four migraine devices that are worn on different areas of the body: the forehead, neck, arm, or head. Each device works in a slightly different way but they all deliver electrical pulses to nerves that can cause migraine.
According to Dr. Silberstein, there are two more devices currently under development: One that’s worn on your neck, which is getting ready to go into clinical trials, and another that’s put in your ear, where it vibrates to activate nerves and control pain. “What’s nice about devices is you can use more than one since they have different mechanisms,” Dr. Silberstein notes. “A lot of my patients find that combining devices is better than using one on its own.”
Another drug-free way to treat migraine is using neurobehavioral techniques such as cognitive behavioral therapy (CBT), which can change how the brain functions, including interrupting and redirecting negative thought patterns and behaviors. “Migraine is a functional disease, meaning it’s not a disease of abnormal brain structure but of abnormal brain function,” Dr. Starling explains. “If we can retrain the brain to function differently through CBT, that’s an excellent treatment approach for migraine. And I love that there are no side effects.”
So far research on CBT for migraine is promising. In 2019, a clinical trial of 60 people found that mindfulness-based cognitive therapy for migraine can significantly decrease disability due to migraine.5 In other words, CBT reduces the impact of migraine on your day-to-day life, which should translate to fewer days spent in bed.
The bottom line: There’s hope for people living with migraine. “If you’ve disengaged from seeking help for your migraine, I strongly encourage you to reengage,” Dr. Starling says. “We have so many new treatment options with many more coming down the pipeline.” A headache specialist can provide the care you need—search the American Migraine Foundation website to find one near you.
1. U.S. National Library of Medicine, Effect of PACAP38/VIP on Migraineurs Measured by Magnetic Resonance 2. Brain, PACAP38 Induces Migraine-Like Attacks in Patients With Migraine Without Aura 3. Cephalalgia, A phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of AMG 301 4. Headache, Oxytocin and Migraine Headache 5. Headache, Does Mindfulness-Based Cognitive Therapy for Migraine Reduce Migraine-Related Disability in People with Episodic and Chronic Migraine?
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