Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.
Martin Kaag RasmussenKjeld MøllgårdPeter A R BorkPia WeikopTina EsmailLylia DriciNicolai J Wewer AlbrechtsenJonathan Frederik CarlsenNguyen P T HuynhNima GhitaniMatthias MannSteven A GoldmanYuki MoriAlexander T CheslerMaiken NedergaardPublished in: Science (New York, N.Y.) (2024)
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.
Keyphrases
- neuropathic pain
- spinal cord
- cerebrospinal fluid
- spinal cord injury
- end stage renal disease
- chronic kidney disease
- induced apoptosis
- newly diagnosed
- traumatic brain injury
- peritoneal dialysis
- prognostic factors
- type diabetes
- cell cycle arrest
- copy number
- functional connectivity
- patient reported outcomes
- multiple sclerosis
- sleep quality
- gene expression
- skeletal muscle
- high fat diet induced
- white matter
- transcription factor
- signaling pathway
- subarachnoid hemorrhage
- endoplasmic reticulum stress
- dna methylation
- metabolic syndrome
- patient reported