Changes in the gene expression profile during spontaneous migraine attacks

Abstract

ObjectiveMigraine occurs in clearly defined attacks and thus lends itself to investigate changes during and outside attack. Gene expression fluctuates according to environmental and endogenous events and therefore is likely to reveal changes during a migraine attack. We examined the hypothesis that changes in RNA expression during and outside of a spontaneous migraine attack exist which are specific to the migraine attack. MethodsWe collected blood samples from 27 migraine patients during an attack, two hours after treatment with subcutaneous sumatriptan, on a headache-free day and after a cold pressor test. All patients were deeply phenotyped, including headache characteristics and treatment effect during the sampling. RNA-Sequencing, genotyping, and steroid profiling was performed on all samples. RNA-Sequences were analyzed at gene level (differential expression analysis) and at network level, and we integrated transcriptomic and genomic data. ResultsWe found 29 differentially expressed (DE) genes between attack and after treatment, after subtracting non-migraine specific genes, i.e. genes related to a general pain/stress response. DE genes were functioning in fatty acid oxidation, signaling pathways and immune-related pathways. Network analysis revealed molecular mechanisms affected by change in gene interactions during the migraine attack, e.g. ion transmembrane transport and response to stress. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. 5HT1 type receptor mediated signaling pathway. InterpretationUsing a paired-sample design, we uniquely investigated intra-individual changes in the gene expression during a migraine attack. We revealed both genes and pathway potentially involved in the pathophysiology of migraine.