Fig. 3

Possible influence of PPIs on CGRP and migraine/headache evolution. CGRP has multiple biological effects, like neuroinflammation, vasodilatation, and antiinflammation. It plays a crucial role in the evolution of headaches. PPI ingestion can lower the levels of CGRP, TRPV1, and Melatonin in the body and have a pro-inflammatory effect. Via a still unknown pathophysiological pathway – or even more than one – PPI use can lead to migraine or severe headache events. This is further influenced by CYP 2C19 metaboliser status, sex, and nutritional and environmental factors like magnesium intake