Calcitonin Gene-Related Peptide Higher in Tear Fluid Compared With Plasma in Migraine

Calcitonin gene-related peptide concentrations were compared via tear fluid collection from patients with either interictal migraine and medicated or unmedicated ictal migraine.

Calcitonin gene-related peptide (CGRP), which plays a major role in the pathophysiology of migraine, is found at higher levels in tear fluid than plasma in patients with migraine vs healthy controls according to study results published in Cephalalgia.

Patients with chronic migraine (n=45) or episodic migraine with or without aura (n=48) were enrolled from an outpatient headache center (age range, 18 to 65 years). Patients with migraine were also subdivided into either interictal migraine and medicated or unmedicated ictal migraine. In addition, a total of 48 healthy controls were recruited. Using enzyme-linked immunosorbent assay testing, the groups were compared with regard to CGRP concentrations in tear fluid and plasma.

The level of CGRP in plasma was 6.81±4.12 pg/ml, whereas levels of CGRP were approximately 138 times higher in tear fluid. Patients with interictal migraine had higher tear fluid CGRP concentrations than healthy controls (1.10±1.27 ng/ml vs 0.75±0.80 ng/ml, respectively; P =.022). Conversely, no difference was found between patients with interictal episodic migraine and chronic migraine with regard to tear fluid CGRP levels (1.09±1.47 ng/ml vs 1.10±0.89 ng/ml, respectively; P =.448).

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In patients with interictal migraine, no correlation was found between frequency of headache and either tear fluid CGRP levels (rho = 0.062; P =.674) or plasma CGRP levels (rho = ±0.141; P =.335). Patients with ictal migraine who were not administered treatment with medication had greater tear fluid levels of CGRP compared with patients with interictal migraine (1.92±1.84ng/ml; P =.102). Patients with ictal migraine who were given treatment with medication had lower levels of CGRP (0.56 ± 0.47 ng/ml; P =.011) vs patients with interictal migraine.

Study limitations were the possibility of misclassification of interictal and preictal migraine types and the small sample size of the study population.

The researchers concluded that the “detection of CGRP in tear fluid is non-invasive, and likely allows a more direct access to CGRP released from the trigeminal nerve than plasma sampling.”


Kamm K, Straube A, Ruscheweyh R. Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls. Cephalalgia. 2019;39(12):1535-1543.