Why do migraines only hurt on one side of the head? New study explains

in collaboration with

Wilfrid Casseron (Neurologist)

A disabling condition affecting millions of people worldwide, migraine is characterized by severe headaches, usually affecting half of the skull. In some cases, the migraine attack will be preceded by an aura, which causes temporary visual or sensory disturbances. In this study, published in the prestigious journal ScienceDanish scientists are trying to shed light on why the pain is one-sided in most migraines.

Proteins transported in the cerebrospinal fluid

For this study, the researchers from the University of Copenhagen worked on mice. They were able to demonstrate that proteins were released by the brain during a migraine with aura and transported via the cerebrospinal fluid (CSF) to the nerves responsible for pain. The study also included MRI scans of the human trigeminal ganglion and, according to the scientists, everything indicates that the pain signaling pathway is the same in mice as in humans.

“We found that these proteins activate a group of sensory nerve cell bodies at the base of the skull called the trigeminal ganglion, which can be described as a gateway to the peripheral sensory nervous system of the skull.” explains Dr Martin Kaag Rasmussen from the Center for Translational Neuromedicine at the University of Copenhagen, first author of the study.

New pain signaling pathway revealed

At the root of the trigeminal ganglion, the barrier that usually prevents substances from entering the peripheral nerves is missing. This allows proteins present in the cerebrospinal fluid to enter and activate the sensory nerves that signal pain, leading to pain and therefore, migraine.Our results suggest that we have identified the main communication channel between the brain and the peripheral sensory nervous system. This is a previously unknown signaling pathway that is important for the development of migraines and may also be associated with other headache-causing diseases.” adds Professor Maiken Nedergaard, lead author of the study.

A study that explains why migraine is one-sided

“Most patients suffer from headache unilateral, and this signaling pathway may help explain why. Our study shows how proteins in the brain are transported. And it’s not to the entire intracranial space, but mainly to the sensory system on the same side, which is why headaches are unilateral.” Martin Kaag Rasmussen further specifies.

The results of the study therefore provide for the first time insight into why migraine only affects one side, which until now was a mystery to scientists.

Towards new treatments to relieve patients?

These proteins could represent new treatment options for patients, according to the scientists. In the study, they analyzed the mixture of substances released during the “aura” stage of a migraine attack.The concentration of 11% of the 1,425 proteins we identified in the cerebrospinal fluid changed during migraine attacks. Among these, 12 proteins whose concentration had increased acted as transmitter substances capable of activating sensory nerves.” according to Martin Kaag Rasmussen.

“We hope that the proteins we have identified – apart from CGRP (a pain-causing protein in migraine and targeted by anti-CGRP antibodiesin monoclonal antibody therapy, editor’s note) – could be used in the design of new preventive treatments for patients who do not respond to available CGRP antagonists. The next step for us is to identify the protein with the greatest potential“.