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Papers: 2 Mar 2024 - 7 Mar 2024

2024 Mar 04

Drug Discov Today


Is calcitonin gene-related peptide (CGRP) the missing link in food histamine-induced migraine? A review of functional gut-to-trigeminovascular system connections.


de Mora F, Messlinger K


Calcitonin gene-related peptide (CGRP) and histamine plasma concentrations increase during migraine attacks. Both mediators are potent vasodilators, and they have been shown to reciprocally contribute to the release of each other in the trigeminovascular system, possibly driving migraine development. A high-histamine-content diet triggers migraine in patients who have histamine degradation deficiency owing to diaminooxidase (DAO) gene mutations. Therefore, studying functional links between exogenous histamine and CGRP seems promising for the understanding of diet-induced migraine generation. Notably, there is a lack of knowledge about the interplay of the enteric nervous system and the spinal/trigeminal somatosensory system with regard to CGRP and histamine. Based on background evidence, we propose that a functional interconnection between exogenous histamine and CGRP contributes to migraine development. Teaser Exogenous histamine may be functionally linked to calcitonin gene-related peptide (CGRP) production, uncovering a possible gut-to-trigeminal connection that may be key to food histamine-induced migraine attacks.