Summary:
This study is breakthrough research related to migraines, explaining the correlation between the neurological symptoms that occur with ‘aura’ and migraine. Aura consists of a set of sensory disturbances that often happen before a migraine begins and can include loss of eyesight, the appearance of zig-zag lines, or flashing lights. The study identifies new proteins that could be responsible for headaches, which could lead to more targeted drug therapy. The researchers analyzed molecules and identified twelve proteins, known as ligands, that bind to receptors on sensory nerves in the trigeminal ganglion. Following a Cortical Spreading Depression (CSD is wave of electrophysiological hyperactivity followed by a wave of inhibition), the currently known cause of aura, the concentrations of several of these proteins more than doubled. Some of these molecules were already linked to migraines, but their exact role and location of action were previously unknown. “Understanding the role of these newly identified ligand-receptor pairs may lead to new pharmacological targets, benefiting the many patients who do not respond to current therapies,” said Martin Kaag Rasmussen, PhD, and author of the study.
Abstract:
Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, ~11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naïve mice in part by CSF-borne calcitonin gene–related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache.
Article Publication Date: 4/7/2024
DOI: 10.1126/science.adl0544
