What’s New in Migraine Research?

There’s still so much we don’t know about migraine, but research into the condition is constantly growing and evolving.

Migraine is a very common neurological condition that affects more than 39 million people in the United States alone. Despite its prevalence, there are still big gaps in our knowledge of what causes migraine and what can be done to treat it.

The good news is that research is constantly being done to better understand migraine. Here are some of the recent developments in the area of headache and migraine research.

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Research into new treatments

CGRP inhibitors

Calcitonin gene-related peptides (CGRP), are small proteins found in the nervous system that are linked to migraine attacks. CGRP inhibitors block these proteins from being released during migraine attacks. Common chronic migraine treatments such as Ajovy, Aimovig, and Emgality use this technology.

However, these treatments are still not available everywhere in the world. Until recently, scientists and doctors believed that CGRP was linked to migraine pain, but they didn’t know exactly how or why this was the case.

A recent study from NYU has observed that CGRP inhibitors may reduce migraine pain because they block CGRP receptors on Schwann cells. Schwann cells are found in the peripheral nervous system and form protective sheaths around peripheral nerves.

Researchers also found that when CGRP proteins bind to Schwann cell receptors these receptors move inside the cell, by way of the cell’s endosomes, and can activate ion channels that send pain signals.

With this new information, scientists are asking questions about how to most effectively target CGRP receptors when they reach the endosome. They plan to pursue more research in this area soon. This research could potentially lead to the development of more effective treatments for people with migraine.

Trigeminal Berve Stimulation

A study called TEAM (Trial for e-TNS for the Acute Treatment of Migraine) tested the therapeutic effects of External Trigeminal Nerve Stimulation (e-TNS) on acute migraine attacks.

The trial was conducted in three phases and saw promising results. Overall, participants reported 14.3% higher rates of pain relief in the 2-hour period after using the device compared to the placebo group.

More participants who used the device reported a complete absence of migraine symptoms in the hours immediately following using the device compared to participants in the placebo group.

The device works by stimulating the trigeminal-vascular system and supraorbital nerve, both of which are involved in migraine attacks. Researchers propose that this sort of stimulation may reduce pain levels by disrupting signals being sent between the brain and these systems.

Trials like these intend to provide migraine relief without the bad side effects that often accompany traditional medications currently prescribed for migraine.

Some medications like triptans for acute attacks and medication for chronic attacks like nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked to worsening or causing migraine episodes in some people.

It’s promising to see a growing interest in the use of external migraine treatments such as e-TNS.

A better understanding of disease mechanisms

Beyond research into specific drugs and treatment options to manage migraine, researchers are also learning more about the factors that contribute to, or exacerbate, migraine.

Genetics

A known risk factor for developing migraine is having a close family member who also lives with migraine. It’s well established that, to some extent, there are genetic factors that make certain individuals more likely to have migraine.

A study recently conducted at the University of Helsinki looked at the DNA of over 800,000 people to identify specific genetic regions that are associated with migraine with aura.

This research is significant because it provides researchers with insight into the genetic changes associated with the two main types of migraine — with and without aura.

Another study revealed an increase in specific genetic proteins present in people who live with migraine including DKK1 and PDGFB. This research suggests that there could be opportunities for therapeutic treatments that target these particular proteins.

Diet

Many people who live with migraine report that certain foods trigger their episodes. One of my own biggest triggers is anything super sweet.

This information informed a 2022 study that had participants who live with migraine track what they ate, as well as their migraine pain and frequency levels.

Scientists then used a “dietary inflammatory index” to calculate inflammatory scores for different foods and nutritional compounds. They found that sticking to an anti-inflammatory diet significantly reduced headache frequency and severity.

Foods on the pro-inflammatory list included sugar, refined carbohydrates, processed meats, and alcohol while anti-inflammatory foods included leafy greens, tomatoes, fruits, fish, poultry, coffee, and tea.

Menstruation and migraine

One common type of migraine is menstrual migraine, which is triggered by hormonal changes during the menstrual cycle. The hormone estrogen has long been implicated in such attacks.

A 2021 study explored this relationship in more detail.

The study explained that when hormonal fluctuations occur (particularly a drop in estrogen that typically happens just right before the period) the neural network associated with migraine pain is activated. This activation lowers the threshold for a migraine episode.

The study also observed that estrogen receptors are activated at the same time as calcitonin gene-related peptide (CGRP) receptors and oxytocin receptors.

This could help explain why CGRP inhibitors are often effective in preventing migraine for many people. It also means that medications that block estrogen and oxytocin may also have implications for treating hormonal migraine.

A 2020 study suggested that there are actually brain structure changes that occur in people who live with hormonal or menstrual migraine.

Their brains showed higher medial prefrontal cortex values. They related these increased values to greater CGRP expression compared to groups that experience other types of migraine.

This research is helping scientists and doctors better understand the involvement of CGRP in menstrual migraine.

What does this all mean?

Migraine research is constantly evolving and growing.

This research helps us understand more about why and how migraine episodes occur. It also helps scientists figure out the factors which may predispose some people to migraine and related disorders.

With a better understanding of the mechanisms associated with migraine comes the potential to develop new treatments and preventive measures.