# Tear fluid calcitonin gene-related peptide (CGRP) is elevated during spontaneous migraine attacks – results from a pilot study

## TL;DR

Tear fluid levels of CGRP increase during migraine attacks, suggesting it could be a useful biomarker for the condition.

## Contribution

This study shows that tear fluid CGRP rises during spontaneous migraine attacks, offering a new non-invasive method for biomarker detection.

## Key findings

- Tear fluid CGRP levels were significantly higher during maximum headache intensity compared to baseline and post-headache.
- The increase in CGRP levels was more pronounced when measured within 3 hours of headache onset.
- Tear fluid CGRP detection may serve as a valid and non-invasive biomarker for migraine.

## Abstract

Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine. The peptide is elevated during interictal and ictal migraine and it might be a biomarker for the disease. However, CGRP detection in blood is limited by dilution and rapid degradation. Therefore, we investigated tear fluid CGRP during spontaneous migraine attacks.

Episodic migraine patients were investigated at two study days. At study day 1, tear fluid was sampled interictally (‘interictal’) and a thorough migraine history was conducted. At study day 2, participants were investigated during a spontaneous migraine attack. Participants were asked to call the study team when experiencing a migraine attack and to present to the outpatient headache center. After arrival, tear fluid was sampled and headache characteristics were assessed. Tear fluid CGRP levels at maximum headache intensity (‘headache’) and after headache improvement (‘post headache’) were analyzed using a commercial CGRP ELISA.

14 female migraine patients (28.4 ± 9.3 years) were included in the analysis. At the time of maximum headache, tear fluid CGRP levels were significantly higher compared to CGRP levels at baseline and after headache resolution (‘interictal’: 1.89 ± 1.68 ng/ml, headache: 2.34 ± 2.20 ng/ml, post headache: 1.23 ± 0.80 ng/ml; p = 0.004). The rise of tear fluid CGRP levels was significantly higher if time since headache onset was shorter (0–3 h: +1.80 ± 1.18 ng/ml, 3–6 h: +0.13 ± 0.93 ng/ml, > 6 h: -1.15 ± 1.63 ng/ml; p = 0.017).

Tear fluid CGRP levels are elevated during spontaneous migraine attacks, suggesting that the detection of CGRP in tear fluid is valid and might be a migraine biomarker in future.