Changes in the gene expression profile during spontaneous migraine attacks

Lisette J A Kogelman,Tom Michoel,Julie Courraud,Thomas F Hansen,Pau Erola,Jes Olesen,Susan Svane Laursen,Alfonso Buil,Katrine Falkenberg

doi:10.1038/s41598-021-87503-5

Abstract

Migraine attacks are delimited, allowing investigation of changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore, we hypothesized that changes in RNA expression during and outside a spontaneous migraine attack exist which are specific to migraine. Twenty-seven migraine patients were assessed during a spontaneous migraine attack, including headache characteristics and treatment effect. Blood samples were taken during attack, two hours after treatment, on a headache-free day and after a cold pressor test. RNA-Sequencing, genotyping, and steroid profiling were performed. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and genomic and transcriptomic data were integrated. We found 29 differentially expressed genes between ‘attack’ and ‘after treatment’, after subtracting non-migraine specific genes, that were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed mechanisms affected by changes in gene interactions, e.g. ‘ion transmembrane transport’. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. ‘5HT1 type receptor mediated signaling pathway’. In conclusion, we uniquely investigated intra-individual changes in gene expression during a migraine attack. We revealed both genes and pathways potentially involved in the pathophysiology of migraine and/or migraine treatment.

Highlights

Considerable manpower, and has not previously been reported
We performed RNA-Sequencing on 27 female migraineurs (17 without aura [migraine without aura (MO)] and 10 with aura [migraine with aura (MA)]) longitudinally at four time points: two to measure gene expression during migraine attack (A and B [Fig. 1]) and, separated by a month two to measure a general pain-stress response after a cold-pressor test (C and D [Fig. 1])
Using RNA-Sequencing we investigated changes in gene expression during a migraine attack and revealed genes and pathways that are potentially involved in the underlying mechanisms of migraine

Summary

Introduction

Considerable manpower, and has not previously been reported. The research facilities at the Danish Headache Center enabled such a design. We here investigated the intra-individual changes in gene expression during a migraine attack which lasts between four and 72 h, enabling a paired-sample design. This design increases the statistical power substantially as factors that are not related to the migraine attack are strongly diminished[12]. Gene expression changes during a cold pressor test in the same individuals, enabled subtraction of genes putatively involved in general pain/stress response. Our hypothesis was that there are specific changes in RNA expression during migraine attack that are not seen during cold pressor test induced pain

Objectives

Methods

Results

Conclusion