Increased CGRP Levels in Tear Fluid May Be Associated With Migraine

A man crying
A man crying
Researchers found data that showed despite the short half-life of calcitonin gene-related peptide levels found in tears, levels were significantly increased in patients with interictal migraine and unmedicated ictal migraine.

According to a study published in Cephalalgia, detection of calcitonin gene-related peptide (CGRP) from tear fluid is a more direct and more sensitive approach than plasma sampling for measuring CGRP released from the trigeminal nerve.

The researchers sought to compare CGRP concentrations in tear fluid and plasma from healthy controls and patients with episodic and chronic migraine; CGRP levels were assessed interictally as well as during treated and untreated migraine attacks.

The study included 48 patients with episodic migraine, 45 patients with chronic migraine, and 48 healthy adults. Patients were further characterized by interictal migraine (30 episodic migraine patients and 19 chronic migraine patients), medicated ictal migraine (12 episodic migraine patients and 13 chronic migraine patients), and unmedicated ictal migraine (3 episodic migraine patients and 10 chronic migraine patients). Tear CGRP was carefully collected from the right and left eyes, and plasma CGRP was drawn from the antecubital vein; CGRP levels were assessed using an enzyme-linked immunosorbent assay kit.

Average tear fluid CGRP levels (0.94±1.11 ng/mL) were 138 times higher than average plasma CGRP levels (6.81±4.12 pg/mL); the difference between eyes was not significantly different. Tear fluid CGRP concentrations were significantly elevated in patients with interictal migraine compared with healthy participants (1.10±1.27 ng/mL vs 0.75±0.80 ng/mL; P =.022); tear CGRP levels did not differ between patients with interictal episodic migraine (1.09±1.47 ng/mL) and patients with interictal chronic migraine (1.10±0.89 ng/mL). Furthermore, there was no correlation between headache frequency and tear CGRP or plasma CGRP levels in patients with interictal migraine.

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Compared with interictal migraine, unmedicated ictal migraine patients had even higher tear fluid CGRP levels (1.92±1.84 ng/mL; P =.102), whereas medicated ictal migraine patients had lower tear fluid CGRP levels (0.56±0.47 ng/mL; P =.011). The latter group was clinically indistinguishable from the healthy participants (P =.609). No significant differences were found in plasma CGRP levels among the 4 groups (interictal migraine, unmedicated ictal migraine, medicated ictal migraine, and control).

Limitations to the study included the difficulty of storing and processing CGRP because it has a half-life of approximately 7 minutes in blood; variations in tear fluid production were not accounted for and may have affected CGRP levels. The investigators did not contact interictal patients following tear fluid collection and therefore the possibility that some interictal patients may have been pre-ictal cannot be excluded. Finally, preprocessing differed between tear fluid and plasma samples, potentially affecting CGRP levels, and the accuracy of enzyme-linked immunosorbent assay may have been less than optimal.

The investigators of the study indicate that CGRP can be detected in tear fluid at concentrations nearly 140 times greater than in plasma sampling, and that tear CGRP levels were significantly increased in patients with interictal migraine and unmedicated ictal migraine independent of headache frequency. Detection of CGRP in tear fluid is a noninvasive approach that is more sensitive and more accessible for collecting CGRP released from the trigeminal nerve.

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Kamm K, Straube A, Ruscheweyh R. Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls [published online June 10, 2019]. Cephalalgia. doi: 10.1177/0333102419856640

This article originally appeared on Neurology Advisor