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

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 similar to 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.

Automated summary

This study aimed to uncover the mechanisms of triptan using metabolomics and transcriptomics in spontaneous migraine attacks. It found three differential metabolites associated with triptan treatment: cortisol, sumatriptan, and glutamine. The change in sumatriptan levels correlated with a change in the expression of GNAI1 and VIPR2 genes, which are known to regulate cAMP levels. Additionally, the study revealed the effect of triptans on fatty acid oxidation, a mechanism previously not associated with triptans but known to be involved in migraine.