Histamine plasma levels from dietary histidine/histamine intake correlate with CGRP in trigeminal tissues
Mora Pérez, Fernando de (Universidad Autónoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Dux, Mária (University of Szeged)
Vogler, Birgit (Friedrich-Alexander-University Erlangen-Nürnberg)
Kuhn, Annette (Friedrich-Alexander-University Erlangen-Nürnberg)
Schramm, Jana (Friedrich-Alexander-University Erlangen-Nürnberg)
Messlinger, Karl (Friedrich-Alexander-University Erlangen-Nürnberg)

Date:	2025
Abstract:	Trigeminal afferents innervating the meninges are likely involved in the generation of headaches and migraine. A major proportion of these afferents can release calcitonin gene-related peptide (CGRP) upon stimulation. Several substances, among them histamine, are known to induce headaches and trigger migraine. In addition to endogenous histamine, high dietary intake of histidine or histamine, or impaired histamine degradation in the gut, can lead to symptoms of histamine intolerance such as headache. However, it remains unclear whether and how dietary histamine impacts the trigeminal system, particularly trigeminal afferents releasing CGRP. In mice supplied with high dietary histidine/histamine, CGRP content in different tissues and CGRP release from the dura mater was utilized as a measure of potential histamine-induced sensitization of trigeminal afferents. After 19-32 days of feeding mice with a diet containing high histidine and histamine levels, CGRP concentrations were measured in plasma as well as in homogenized samples of ileum, trigeminal ganglia, spinal medulla and cerebellum, and compared with those from a control group fed a standard chow. CGRP content and release data were correlated with previously analysed histamine content and release data. Likewise, CGRP release from the cranial dura mater stimulated with the TRPV1 receptor agonist capsaicin was determined using our validated hemisected cranial preparation. Mice fed high histamine-histidine diets exhibited an increased trigeminal ganglion CGRP concentration that correlated with diet-derived plasma histamine levels. The capsaicin stimulated CGRP release from the dura mater was higher in animals supplied with high histidine/histamine diet compared to control animals. An exponentially higher amount of dietary histidine likely converted into histamine in the gut appeared to be the main contributor to modulating CGRP levels. Separating for sexes and normalizing to the body weight of the animals, this difference was attributable to male mice. High dietary histidine or histamine, by elevating plasma histamine levels, cause increased CGRP concentrations and ongoing CGRP release from peptidergic afferents in trigeminal tissues. Exogenous histamine-induced sensitization of trigeminal afferents may facilitate headache generation and contribute to trigger migraine attacks. The online version contains supplementary material available at 10. 1186/s10194-025-02178-x.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Calcitonin gene-related peptide ; CGRP ; Headache ; Histamine intolerance ; Migraine ; Trigeminal sensitization
Published in:	Journal of headache and pain, Vol. 26 (November 2025) , art. 258, ISSN 1129-2377

DOI: 10.1186/s10194-025-02178-x
PMID: 41233718

11 p, 1.9 MB

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