Researchers at the University of North Carolina School of Medicine have identified that a peptide known as CGRP can disrupt the flow of cerebrospinal fluid through the brain’s lymphatic vessels, a disruption that appears to contribute to the pain associated with migraine episodes. The findings were published in the Journal of Clinical Investigation (JCI).
Evidence from various studies indicates that during a migraine attack, the amount of CGRP molecules rises. These molecules interact with sensory neurons in the meninges to amplify pain signals. To understand the precise mechanism by which CGRP induces pain, scientists designed an experiment using two groups of mice for comparison.
One group consisted of genetically engineered mice that were resistant to the effects of CGRP, while the second group served as a control and had no genetic alterations. All mice were placed in a two-chamber setup: one brightly lit and the other dim. The CGRP-resistant mice tolerated bright light better, whereas the control mice showed a preference for the darker chamber. This observation aligns with the well-known migraine trigger of light sensitivity in many people who experience migraines.
In a study using cell culture techniques, researchers examined how a key protein, BE-cadherin, is distributed in the spaces between endothelial cells lining lymphatic vessels. BE-cadherin contributes to the cohesion of lymphatic endothelial cells and regulates the permeability of the vessel walls, determining how freely fluids such as cerebrospinal fluid can cross between cells and enter the lymphatic network.
The investigation revealed that when CGRP is present, lymphatic endothelial cells organize conspicuous VE-cadherin lines that impede fluid passage between neighboring cells. The researchers proposed that a migraine may stem from the impediment of cerebrospinal fluid drainage from the brain’s meningeal lymphatic system, which otherwise would allow immune cells to patrol the meninges and support the brain’s protective environment.
These findings add a new layer to the understanding of migraine physiology by linking CGRP activity with changes in the brain’s fluid drainage pathways and immune surveillance. The results suggest that restoring normal lymphatic flow and endothelial cell dynamics could be a potential avenue for mitigating migraine pain, especially in cases where CGRP plays a prominent role.
Overall, the study emphasizes the importance of the meningeal lymphatic system in maintaining a balanced brain environment. By clarifying how CGRP affects fluid movement and immune cell access, researchers are opening doors to targeted strategies that may complement existing migraine therapies and offer relief to individuals who struggle with this condition.