Identification of Disease- and Headache-Specific Mediators and Pathways in Migraine Using Blood Transcriptomics

The mechanisms underlying migraine susceptibility and headache are still not fully understood. Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) of migraineurs in a self-controlled manner during and between attacks to identify headache-specific pathophysiological pathways. In addition, metabolite measurements were performed from plasma samples taken as a same time. Twenty-four migraineurs were recruited and blood samples were collected during headache and in a headache-free period. Control samples were collected from 13 age- and gender-matched healthy volunteers. RNA was isolated and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Metabolomic measurement was performed with a Biocrates MxP Quant 500 Kit. We have identified 144 differentially-expressed genes between headache and headache-free samples and 163 between symptom-free patients and healthy controls. Network analysis revealed that enriched pathways and processes included inflammation, cytokine activity and mitochondrial function. Significant differences were found in plasma levels of spermine, spermidine, lactate, succinate and aconitate, as well as methionine sulfoxide. In conclusion, we demonstrated a considerable difference between PBMC transcriptome and various plasma metabolites of healthy controls and migraineurs even in the headache-free period. Our results suggest that enhanced immune cell activity and oxidative stress generation plays a role in migraine susceptibility and headache-generation.