For years migraine has kept millions of people in check, “hitting and running” like the most skilled and elusive rogue. Now, a team of Danish researchers may have finally shed light on its mechanisms, with a discovery that could mark a turning point for therapies.
The mystery of unilateral migraine
Migraines affect millions of people around the world. A peculiar feature of this condition is the so-called “unilateral pain”, often preceded by an aura (temporary visual or sensory disturbances). Until now, the mechanism underlying this phenomenon had remained an enigma to the scientific community.
A new study conducted on mice by researchers from the University of Copenhagen, the Rigshospitalet and the Bispebjerg Hospital has finally revealed the mystery. Research has shown for the first time that proteins released by the brain during migraine aura are transported by cerebrospinal fluid to the nerves that signal pain.
The key role of the trigeminal ganglion
Martin Kaag Rasmussen, first author of the study (that I link to you here), explains:
We found that these proteins activate a group of sensory nerve cell bodies at the base of the skull, the so-called trigeminal ganglion, which can be described as a gateway to the peripheral sensory nervous system of the skull.
At the root of the trigeminal ganglion, the barrier that usually prevents substances from entering the peripheral nerves is absent. This allows substances in the cerebrospinal fluid to enter and activate sensory nerves that signal pain, resulting in migraines.
The voice of pain
This finding also offers a plausible explanation for the unilateral nature of migraine. Rasmussen says: “Our study of how brain proteins are transported shows that the substances are not transported to the entire intracranial space, but mainly to the sensory system on the same side, thus causing the one-sided headache typical of this event.”
Using cutting-edge techniques such as mass spectrometry, researchers analyzed the cocktail of substances released during the aura phase of a migraine attack. They identified 1.425 proteins in cerebrospinal fluid, of which 11% showed changes in concentration during migraine attacks.
Among the proteins identified is the CGRP, already known for its role in migraines and used in existing treatments. But she's not the only one, obviously. The researchers also discovered a number of other proteins that could pave the way for new treatment options.
Migraine, next steps in research
The research team is now working to identify the protein with the greatest therapeutic potential. Rasmussen hopes to identify proteins that trigger migraine phenotypes. Her team will then proceed with challenge tests in humans to determine whether exposure to one of the identified proteins can trigger a migraine attack.
From there it could be a short step to the development of targeted treatments. If some of these proteins can actually trigger migraine attacks in humans, they will become crucial targets for new preventative and treatment therapies.
In summary: we will soon give migraines a headache
The discovery of this new communication pathway between the brain and the peripheral nervous system represents a significant advance in our understanding of migraine. It offers both explanation for the symptoms and direction for finding more effective treatments.
The journey to fully understanding and treating migraine continues, but this discovery marks a crucial turning point. Soon, for millions of people, the one-sided pain of migraines could become a thing of the past.
