‘This is What Drives the Migraine Headache’ – Study Reveals ‘Missing Link’ Cause Behind Some Migraines

By: Sam Watanuki | Published: Jul 05, 2024

Migraines affect over a billion people annually, with about 25% experiencing “auras.” These short-lived neurological symptoms include seeing lights, hearing sounds, or feeling tingling sensations.

Scientists have linked these auras to cortical spreading depression (CSD), which involves waves of abnormal brain activity.

The Role of Cortical Spreading Depression

CSD triggers migraine auras by creating waves of abnormal activity that deactivate neurons. This process releases chemicals into the cerebrospinal fluid (CSF), the substance that cushions the brain.

A digital illustration of proteins building up around a brain cell

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These chemicals are believed to stimulate pain-detecting nerves, causing migraine headaches.

The Trigeminal Ganglion: A New Pathway

Researchers have identified a new pathway that could explain how these chemicals reach pain-detecting nerves. The trigeminal ganglion, a cluster of neurons transmitting signals from the face and jaw to the brain, plays a major role.

A digital illustration of neurons and synapses within the brain

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This nerve bundle also provides a route for CSF and its molecules to travel outside the brain.

Experimental Evidence from Mouse Studies

In a study published in Science, researchers used genetically modified mice to trace the flow of CSF.

Researcher notes observations while watching a mouse in a laboratory

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The mice’s neurons glowed in the presence of calcium, allowing scientists to observe the CSF’s path. They injected a tracer into the mice’s brains and tracked its movement to the trigeminal ganglion.

Observing the Trigeminal Ganglion

Four minutes after injection, the CSF appeared in the trigeminal ganglion, followed by increased calcium activity.

A white mouse with red eyes surrounded by shredded pieces of paper as bedding.

Source: Nature_Blossom/Pixabay

This direct evidence confirmed that CSF can carry molecules from the brain to peripheral nerves through this channel. The ganglion’s structure near the brainstem facilitates this interaction.

Connecting Auras to Migraines

Researchers demonstrated that CSD increases CSF flow, carrying more proteins to the trigeminal ganglion. These proteins are known drivers of pain and inflammation.

Human brain colored different hues of blue

Source: Mind Valley

During auras, proteins activate sensory nerves, leading to migraine headaches. This finding bridges the gap between the aura phase and the headache.


The Significance of CGRP

Of the 12 proteins identified, only calcitonin gene-related peptide (CGRP) is currently targeted by migraine therapies. Medications blocking CGRP function relieve symptoms for about half of migraine patients.

A man sat in a black chair with a brain-scanning device on his head. There are two female doctors in the room with him. One is looking at the brain scanning device and the other is writing on a notepad.

Source: DC Studio/Freepik

However, this leaves millions without effective treatment, highlighting the need for new therapeutic targets.


Potential for New Treatments

Study author Martin Kaag Rasmussen believes these findings could lead to new treatment options. Identifying the specific molecules responsible for migraines may help develop therapies for patients who don’t respond to current treatments.

Illustration of brain

Source: Canva

This discovery opens new avenues for migraine research and treatment.


Broader Implications of the Study

Andrew Russo, a neurology professor at the University of Iowa, suggests that this new molecular pathway could have broader implications.

Two people meet in an office with their laptops and strategize by collaborating on a white piece of paper

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Understanding how molecules travel from the brain to peripheral ganglia may inform research on other neurological conditions. This discovery has the potential to impact various fields of study.


Challenges and Future Research

While promising, these findings are still only based on mouse models. The human brain’s complex structure, with its numerous folds, differs significantly from the smooth brain of a mouse.

Doctors examining several brain scans

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Researchers need to replicate these findings in humans or more human-like animal models to validate the results.


Next Steps in Migraine Research

The next phase involves studying these processes in humans and examining the new pain-triggering proteins identified.

Illustration of neurons in the brain affected by Alzeimer’s

Source: Freepik

This research could lead to better diagnostic tests and treatments for migraines and other headache disorders.


A New Hope for Migraine Sufferers

This groundbreaking study provides, at the very least, hope for millions of migraine sufferers. By uncovering a previously unknown pathway, researchers have paved the way for new treatments and improved understanding of migraine mechanisms.

An adult man sitting on a bed, holding his head in a gesture of pain or discomfort, with a pained expression on his face. He is wearing a white t-shirt and plaid pajama pants, with bedding that has a striped pattern

Source: Andrea Piacquadio/Pexels

Future research will continue to build on these findings, potentially transforming migraine therapy.