# A Review of the Biochemical Diagnostic Biomarkers in Migraine: New Perspectives in Diagnostics

**Authors:** Karolina Różycka, Natalia Siwak, Aleksandra Rucka, Joanna Bielewicz, Konrad Rejdak

PMC · DOI: 10.1155/prm/9478767 · Pain Research & Management · 2025-12-08

## TL;DR

This review explores biochemical biomarkers for migraine, highlighting potential candidates like CGRP and PACAP for improved diagnosis.

## Contribution

The paper identifies promising biomarkers and emphasizes the need for standardized methods and multi-biomarker panels.

## Key findings

- CGRP and PACAP are highlighted as potential diagnostic biomarkers for migraine.
- Other agents like PTX3 and cytokines show promising but not yet definitive value.
- Standardized methods and multi-biomarker panels from blood, saliva, and urine are suggested for future research.

## Abstract

The aim of this review was to evaluate studies concerned with substances which can be used as biochemical biomarkers of migraine (MH). Current MH diagnosis is based on the clinical criteria provided by International Headache Society (IHS) in the third edition of International Classification of Headache Disorders from 2018. Biochemical biomarkers could be useful in more precise and differential diagnosis which is important for proper choice of treatment.

Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines (PRISMA) were applied. MEDLINE (via PubMed), Web of Science, and Embase databases were searched in the recent 5 years. Studies exclusively focused on MH and biochemical biomarkers in adults and children, which can be applied as diagnostic tools, were conducted.

Finally, 31 researchers were assessed and discussed. Most of the presented studies were focused on calcitonin gene–related peptide (CGRP), pituitary adenylate cyclase‐activating peptide (PACAP), pentraxin 3 (PTX3), cytokines, and markers related to mitochondrial metabolism, making CGRP and PACAP possible diagnostic biomarkers. However, other agents have promising value.

Based on the available studies, there are no specific substances which could be proposed as potential, practical, and useful biomarkers in HD. However, a few agents could be promising. The standardization of methodology would help in further investigations. Panels of biomarkers, easily obtained from blood but also from saliva and urine, could be interesting purposes for research in future.

## Linked entities

- **Proteins:** CALCA (calcitonin related polypeptide alpha), ADCYAP1 (adenylate cyclase activating polypeptide 1), PTX3 (pentraxin 3)
- **Diseases:** migraine (MONDO:0005277)

## Full-text entities

- **Genes:** CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, ADCYAP1 (adenylate cyclase activating polypeptide 1) [NCBI Gene 116] {aka PACAP}, PTX3 (pentraxin 3) [NCBI Gene 5806] {aka TNFAIP5, TSG-14}
- **Diseases:** HD (MESH:D006816), MH (MESH:C535694), Headache Disorders (MESH:D020773), Migraine (MESH:D008881), Headache (MESH:D006261)

## Full text

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## Figures

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## References

69 references — full list in the complete paper: https://tomesphere.com/paper/PMC12767422/full.md

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Source: https://tomesphere.com/paper/PMC12767422