• Katharina Kamm, Andreas Straube, and Ruth Ruscheweyh.
• Department of Neurology, Ludwig-Maximilians-University Hospital, Munich, Germany.
• Cephalalgia. 2019 Oct 1; 39 (12): 1535-1543.

BackgroundCalcitonin gene-related peptide (CGRP) released from trigeminal nerve fibres indicates trigeminal activation and has a key role in migraine pathophysiology. The trigeminal nerve directly innervates the eye. Therefore, in this study, we compared Calcitonin gene-related peptide in tear fluid of migraine patients and healthy controls.MethodsCalcitonin gene-related peptide concentrations in tear fluid and plasma of 48 episodic and 45 chronic migraine patients and 48 controls were assessed using ELISA.ResultsCalcitonin gene-related peptide levels in tear fluid (0.94 ± 1.11 ng/ml) were ∼140 times higher than plasma concentrations (6.81 ± 4.12 pg/ml). Tear fluid CGRP concentrations were elevated in interictal migraine patients (1.10 ± 1.27 ng/ml, n = 49) compared to controls (0.75 ± 0.80 ng/ml, p = 0.022). There was no difference in tear fluid CGRP levels between interictal episodic and chronic migraine patients (episodic: 1.09 ± 1.47 ng/ml, n = 30 and chronic: 1.10 ± 0.89 ng/ml, n = 19) and no correlation of tear fluid CGRP levels with headache frequency in interictal patients (rho = 0.062, p = 0.674). Unmedicated ictal migraine patients had even more elevated tear fluid CGRP levels than interictal migraine patients (1.92 ± 1.84 ng/ml, n = 13, p = 0.102), while medicated ictal migraine patients had lower levels (0.56 ± 0.47 ng/ml, n = 25, p = 0.011 compared to interictal patients), which were undistinguishable from controls (p = 0.609). In contrast to tear fluid, no significant group differences were found in plasma CGRP levels.ConclusionTo the best of our knowledge, this study shows, for the first time, increased CGRP tear fluid levels in migraine patients compared to healthy subjects. Detection of calcitonin gene-related peptide in tear fluid is non-invasive, and likely allows a more direct access to CGRP released from the trigeminal nerve than plasma sampling.

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