Migraine Study Reveals How Brain Fluid Molecules Flow Through the Brain To Trigger Headache, Gives Rise to Potential Treatments

The complex molecular paths that connect visual auras to migraine headaches have been uncovered in a new study. This opens up new treatment options.

The study, published in Science, shows that cerebrospinal fluid (CSF) is important in the transmission of migraine pain.

Migraine Study Reveals How Fluid Molecules Flows Through the Brain to Trigger Headache — Unsplash/ Nik Shuliahin

Getting to the Bottom of Migraines

Millions of people around the world get migraines, and one-third of them have visual disturbances called auras before the pain. These auras can show up as blind spots, flashing lights, or hazy vision, and they usually start about an hour before the headache. The chemical link between these auras and the following headache has been hard to find until now.

A new study on mice shows that molecules moving through cerebrospinal fluid (CSF), which feeds the brain and spinal cord, play a significant role in migraine pain. The team, led by neuroscientist Maiken Nedergaard from the University of Copenhagen, put capsaicin, a chemical found in chili peppers that causes pain, into the brains of mice.

Within six minutes, this shot turned on neurons in the trigeminal ganglia, which are in charge of feeling and pain in the face. This means that CSF can physically send pain messages from the brain to the trigeminal ganglia.

Cortical spreading depression (CSD) is a wave of abnormal firing that moves across the cortex of the brain and is often the start of a migraine. The brain doesn't have any pain sensors, but the researchers thought that signals from CSD might be able to reach the trigeminal ganglia and cause migraines.

To see if this idea was true, the researchers caused CSD in one part of the mouse brain and inserted a fluorescent tracer to see how molecules moved. They discovered that more of the tracer in the trigeminal ganglia on the side was activated. This suggests that CSD changes the flow of CSF and, in turn, pain signals.

Protein Involvement and Potential Treatments

The study found 21 proteins in the CSF that doubled in amount after CSD. One of these proteins is calcitonin gene-related peptide (CGRP), which is known to be linked to migraines. This finding shows that more than one molecule could help find new ways to treat migraines, going beyond the current focus on CGRP-based treatments.

A translational neuroscientist at Harvard Medical School named Rami Burstein says it is possible to make someone feel like they have a headache by changing the chemical environment around neurons in the trigeminal ganglion. This discovery could lead to new medicines targeting the chemicals involved in migraine pathways.

For many people who get headaches, stopping them before they happen is just as important as treating them when they do occur. Many medicines and natural remedies can help avoid migraines, but only a few have been approved by the FDA. Some are anticonvulsants (like divalproex and topiramate) and CGRP inhibitors (made just for headaches). Others are beta-blockers (like propranolol and timolol).

This critical study helps us learn more about migraines and lays the groundwork for improving treatments. By focusing on the found molecular pathways, new therapies could be created that help millions of migraine sufferers around the world.