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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 \u2018attack\u2019 and \u2018after treatment\u2019, 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. \u2018ion transmembrane transport\u2019. Integration of genomic and transcriptomic data revealed pathways related to sumatriptan treatment, i.e. \u20185HT1 type receptor mediated signaling pathway\u2019. 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.<\/jats:p>","DOI":"10.1038\/s41598-021-87503-5","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T06:18:05Z","timestamp":1618467485000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Changes in the gene expression profile during spontaneous migraine attacks"],"prefix":"10.1038","volume":"11","author":[{"given":"Lisette J. 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