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Open Access 01-12-2024 | Migraine | Research

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

Authors: Gabriel Gárate, Julio Pascual, Marta Pascual-Mato, Jorge Madera, María Muñoz-San Martín, Vicente González-Quintanilla

Published in: The Journal of Headache and Pain | Issue 1/2024

Abstract

Background

Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker.

Methods

Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age.

Results

Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women.

Conclusions

We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations.

Graphical Abstract

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Title: Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience
Authors: Gabriel Gárate
Julio Pascual
Marta Pascual-Mato
Jorge Madera
María Muñoz-San Martín
Vicente González-Quintanilla
Publication date: 01-12-2024
Publisher: Springer Milan
Keywords: Migraine
Biomarkers
Published in: The Journal of Headache and Pain / Issue 1/2024
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-024-01769-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

Abstract

Background

Methods

Results

Conclusions

Graphical Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Graphical Abstract

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