Multi-omic analyses of triptan-treated migraine attacks gives insight into molecular mechanisms

Lisette J.A. Kogelman*, Katrine Falkenberg, Filip Ottosson, Madeleine Ernst, Francesco Russo, Valdemar Stentoft-Hansen, Samuel Demharter, Peer Tfelt-Hansen, Arieh S. Cohen, Jes Olesen, Thomas Folkmann Hansen

*Corresponding author af dette arbejde

Abstract

Migraine is a common, polygenic disorder that is characterized by moderate to severe headache attacks. Migraine attacks are commonly treated with triptans, i.e. serotonin receptor agonists. However, triptans are effective in ~ 60% of the population, and the mechanisms of triptans are debated. Here, we aim to expose the mechanisms of triptan using metabolomics and transcriptomics in spontaneous migraine attacks. We collected temporal multi-omics profiles on 24 migraine patients, using samples collected at a migraine attack, 2 h after treatment with a triptan, when headache-free, and after a cold-pressor test. Differential metabolomic analysis was performed to find metabolites associated with treatment. Their effect was further investigated using correlation analysis and a machine learning approach. We found three differential metabolites: cortisol, sumatriptan and glutamine. The change in sumatriptan levels correlated with a change in GNAI1 and VIPR2 gene expression, both known to regulate cAMP levels. Furthermore, we found fatty acid oxidation to be affected, a mechanism known to be involved in migraine but not previously found in relation to triptans. In conclusion, using an integrative approach we find evidence for a role of glutamine, cAMP regulation, and fatty acid oxidation in the molecular mechanisms of migraine and/or the effect of triptans.

OriginalsprogEngelsk
Artikelnummer12395
TidsskriftScientific Reports
Vol/bind13
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - dec. 2023

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