No one really knows what causes migraines, but a number of studies have begun to piece together the mechanisms behind these hellish headaches.
There is evidence that short chains of amino acids called calcitonin gene-related peptides (CGRPs) may be the evil puppeteers behind painful migraine attacks, and treatments targeting CGRP are already on the market. There is also some evidence that malfunctions in the brain’s fluid drainage systems may sometimes be involved.
A research team from the University of North Carolina School of Medicine has found evidence that CGRP may be directly involved in blocking the drainage of cerebrospinal fluid from the brain, creating the pressure and pain felt during migraine.
“Our study highlighted the importance of the brain’s lymphatic system in the pathophysiology of migraine pain,” explains physiologist Kathleen Caron. “We found that migraine pain is influenced by altered interactions with immune cells and by CGRP, which prevents cerebrospinal fluid from leaking out of the meningeal lymphatics.”
This helpful neuropeptide is abundant in layers of brain tissue called the meninges during migraine attacks. Through a series of tests on mice and their cultured cells, the researchers found that CGRP not only transmitted pain between neurons, but also blocked the flow of fluid from the brain’s lymphatic system, which could explain the feeling of pressure associated with migraine.
In a mouse model of nitroglycerin-induced migraine, mice genetically engineered to lack lymphatic CGRP receptors—thus making them “immune” to the neuropeptide—showed a significant reduction in chronic migraine pain as measured using a grimace scale.
Cerebrospinal fluid (CSF) is stored in the nervous system in a number of chambers connected by a complex network of meningeal lymphatic vessels. These vessels facilitate the flow of fluid to brain tissue in the same way that a garden hose trickles water onto each plant in a garden. In addition, these lymphatic “seepers” also carry immune cells to the brain’s protective layer, where they can patrol the brain like tiny gardeners for parasites and diseases.
When the researchers injected CGRP directly into a crucial reservoir of CSF in the brains of mice with migraine models, pores along the VMLs closed, causing the brain’s plumbing to back up and dramatically reducing the amount of CSF flowing out of the skull.
While this new study adds to the growing body of evidence implicating CGRP in migraine and migraine pain in particular, it is still unclear what triggers this systemic breakdown. However, it does provide insight into why migraine therapies that target CGRP are effective and where in the body they make this difference.
The next step is to determine whether these lymphatic system problems might help explain why three times as many women suffer from migraines as men.
““Given that lymphatic dysfunction also has a high prevalence in women, it is tempting to speculate that neurological disorders such as migraine might be driven by sex differences in meningeal lymphatic vascularization,” Caron says.
“If this were true, then novel therapeutic strategies or drug targets that improve meningeal lymphatic and glymphatic flow in women would be desirable.”
This research was published in the Journal of clinical investigation.
News Source : www.sciencealert.com
Gn Health
