For the millions who suffer from migraines, relief can seem out of reach. Now, however, researchers from the University of North Carolina School of Medicine may be able to change that. Their findings published in the Journal of Clinical Investigation reveal the potential cause of migraines, explaining why they hurt so much and how to treat them.

The offender? A small protein called calcitonin gene-related peptide, or CGRP. While scientists have known about the protein’s involvement in migraine pain for a while, this new study lays bare its surprising effect on the brain’s plumbing system.

“Our study has highlighted the importance of the brain’s lymphatic system in the pathophysiology of migraine pain,” says Kathleen M Caron, PhD, the Frederick L. Eldridge Distinguished Professor and chair of the Department of Cell Biology and Physiology and senior author on the study, in a media release. “We found that migraine pain is influenced by altered interactions with immune cells and by CGRP preventing cerebrospinal fluid from draining out of the meningeal lymphatic vessels.”

What does all that mean for migraine sufferers?

According to Dr Beverly Cheserem, a consultant neurosurgeon at Aga Khan University Hospital, Nairobi, the brain has its own drainage system -- kind of like the pipes in the sinks and toilets. This system is called the lymphatic system, and it helps remove excess fluid (cerebrospinal fluid) and allows immune cells to patrol the brain’s protective layers. During a migraine attack, CGRP levels increase sharply in these areas.

The surge in the proteins changes how the brain’s drainage vessels work. The proteins tighten up the pipes so that fluid can’t flow as easily. CGRP on its own is beneficial in that it acts on the walls of blood vessels and relaxes them to reduce blood pressure and increase blood flow but in excess, it can cause extreme pain and inflammation, hence migraine attacks.

Research published in the journal Neurology revealed that women with chronic migraine have heightened levels of CGRP than women who only had little to no migraine pain. The women with chronic migraine had high levels of CGRP in their blood even when not having a migraine attack.

While this research is a big step forward, according to the study authors, there’s still more to learn. 

The findings raise intriguing questions about why migraines affect women so much more frequently than men. For the millions living with migraines, this research offers hope. By understanding the intricate mechanisms behind the pain, scientists are one step closer to developing more effective treatments.

“This study opens up a new avenue in migraine treatment by highlighting the meningeal lymphatic system as a potential target for therapeutic intervention. The findings suggest that treatments aimed at regulating or blocking CGRP signalling reduce inflammation and pain in the nervous system of people who suffer migraine attacks. This could lead to more precise and effective treatments, bringing relief to millions of migraine sufferers worldwide,” reads the press release.