Evidence of Hypoxia Signaling and Endothelial Activation in Migraine: Relationships Between HIF-1α, VEGF-A, and Arginine Metabolism.

Migraine is a common neurovascular disorder that causes significant disability. This study explored the role of hypoxia signaling and endothelial dysfunction in chronic migraine. Researchers analyzed plasma samples from 28 migraine patients and 28 healthy controls. They measured levels of HIF-1α, VEGF-A, and arginine pathway metabolites. Results showed that migraine patients had significantly higher levels of VEGF-A and HIF-1α compared to controls. VEGF-A effectively distinguished migraine status with an AUC of 0.973. HIF-1α also showed good discrimination with an AUC of 0.794. The arginine-to-citrulline ratio was higher in migraine patients, while ornithine levels were lower. In multivariable analyses, both VEGF-A and HIF-1α were strongly linked to migraine status. These findings suggest that hypoxia-related signaling and endothelial activation may influence chronic migraine. Further research is needed to confirm these findings and their implications for treatment. Clinical relevance: This research indicates that targeting hypoxia signaling may improve chronic migraine treatments.