Dynamic fluctuations of salivary CGRP levels during migraine attacks : association with clinical variables and phenotypic characterization
Alpuente, Alicia (Hospital Universitari Vall d'Hebron)
Gallardo López, Victor José (Vall d'Hebron Institut de Recerca (VHIR))
Asskour, Laila (Vall d'Hebron Institut de Recerca (VHIR))
Caronna, Edoardo (Vall d'Hebron Institut de Recerca (VHIR))
Torres-Ferrús, Marta (Vall d'Hebron Institut de Recerca (VHIR))
Pozo-Rosich, Patricia (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2024
Resum:	Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables. A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype. A total of 44 migraine patients were included (90. 9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19. 4 [5. 8], p = 0. 001) and quadratic terms of time (-19. 1 [6. 0], p = 0. 002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18. 5 [6. 2], p = 0. 005; quadratic-term: 19. 2 [6. 8], p = 0. 005) was also found. Molecular phenotyping revealed that 72. 7% (32/44) of patients presented only CGRP-dependent attacks, while 27. 3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (p < 0. 05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks. Our study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.
Ajuts:	Ministerio de Economía y Competitividad PI16/01525
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Migraine ; Salivary CGRP ; Biomarker ; Endophenotyping ; Personalized medicine
Publicat a:	Journal of headache and pain, Vol. 25 Núm. 1 (April 2024) , ISSN 1129-2377

DOI: 10.1186/s10194-024-01772-9
PMID: 38637736

10 p, 2.6 MB

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