Background Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology and is a marker of trigeminal activity. We investigated tear fluid CGRP levels interictally and ictally using the glyceryl trinitrate (GTN) experimental migraine model. Methods Study participants were assessed interictally and during an experimental headache using GTN. Interictal tear fluid CGRP levels were assessed in episodic migraine (EM) patients and healthy controls (HC). At the day of experimental headache, tear fluid was sampled in EM patients before and after intravenous GTN application. Participants were free to use their usual abortive medication if needed. Tear fluid CGRP levels were analyzed using two different ELISAs. Results 26 EM patients and 20 healthy controls were examined interictally. Interictal tear fluid CGRP was significantly higher in EM patients compared to HCs (Abbexa® CGRP ELISA: interictal EM patients: 2.78 ± 1.99 ng/ml, HC: 1.35 ± 0.78 ng/ml, U = −2.969, p = 0.003). 17 EM patients were analyzed after intravenous GTN. Tear fluid CGRP levels were significantly elevated at maximum headache compared to baseline (Abbexa® CGRP ELISA: 3.84 ± 1.96 ng/ml vs. 2.78 ± 2.38 ng/ml, p = 0.025; Cusabio® CGRP ELISA: 1.43 ± 0.96 ng/ml vs. 0.75 ± 0.77 ng/ml, p < 0.001). Seven patients developed a headache with an intensity ≥ 5 on the numerical rating scale (NRS) and showed a significantly higher rise in tear fluid CGRP compared to patients with a headache < 5 on the NRS (Abbexa® CGRP ELISA: + 2.11 ± 2.14 ng/ml vs. + 0.32 ± 1.33 ng/ml, p = 0.033; Cusabio® CGRP ELISA: + 1.45 ± 0.81 ng/ml vs. + 0.09 ± 0.53 ng/ml; p < 0.001). Tear fluid CGRP levels were significantly more reduced after intake of abortive medication than after spontaneous headache improvement (Abbexa® CGRP ELISA: −0.82 ± 1.26 ng/ml vs. 1.24 ± 2.06 ng/ml, p = 0.014; Cusabio® CGRP ELISA: −0.66 ± 1.27 ng/ml vs. −0.12 ± 0.24 ng/ml, p = 0.033). Conclusion The present results demonstrate validity of tear fluid CGRP assessment during experimental migraine, detecting a rise of tear fluid CGRP levels during GTN-induced headache. The intake of abortive medication reduced tear fluid CGRP levels significantly more than spontaneous headache improvement. Graphical abstract

Tear fluid CGRP rises during glyceryl trinitrate-induced headache in migraine patients

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2025年11月14日

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Katharina Kamm,
Marie-Christine Khorsandian,
Andreas Straube,
Ruth Ruscheweyh

摘要

Background

Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology and is a marker of trigeminal activity. We investigated tear fluid CGRP levels interictally and ictally using the glyceryl trinitrate (GTN) experimental migraine model.

Methods

Study participants were assessed interictally and during an experimental headache using GTN. Interictal tear fluid CGRP levels were assessed in episodic migraine (EM) patients and healthy controls (HC). At the day of experimental headache, tear fluid was sampled in EM patients before and after intravenous GTN application. Participants were free to use their usual abortive medication if needed. Tear fluid CGRP levels were analyzed using two different ELISAs.

Results

26 EM patients and 20 healthy controls were examined interictally. Interictal tear fluid CGRP was significantly higher in EM patients compared to HCs (Abbexa® CGRP ELISA: interictal EM patients: 2.78 ± 1.99 ng/ml, HC: 1.35 ± 0.78 ng/ml, U = −2.969, p = 0.003). 17 EM patients were analyzed after intravenous GTN. Tear fluid CGRP levels were significantly elevated at maximum headache compared to baseline (Abbexa® CGRP ELISA: 3.84 ± 1.96 ng/ml vs. 2.78 ± 2.38 ng/ml, p = 0.025; Cusabio® CGRP ELISA: 1.43 ± 0.96 ng/ml vs. 0.75 ± 0.77 ng/ml, p < 0.001). Seven patients developed a headache with an intensity ≥ 5 on the numerical rating scale (NRS) and showed a significantly higher rise in tear fluid CGRP compared to patients with a headache < 5 on the NRS (Abbexa® CGRP ELISA: + 2.11 ± 2.14 ng/ml vs. + 0.32 ± 1.33 ng/ml, p = 0.033; Cusabio® CGRP ELISA: + 1.45 ± 0.81 ng/ml vs. + 0.09 ± 0.53 ng/ml; p < 0.001). Tear fluid CGRP levels were significantly more reduced after intake of abortive medication than after spontaneous headache improvement (Abbexa® CGRP ELISA: −0.82 ± 1.26 ng/ml vs. 1.24 ± 2.06 ng/ml, p = 0.014; Cusabio® CGRP ELISA: −0.66 ± 1.27 ng/ml vs. −0.12 ± 0.24 ng/ml, p = 0.033).

Conclusion

The present results demonstrate validity of tear fluid CGRP assessment during experimental migraine, detecting a rise of tear fluid CGRP levels during GTN-induced headache. The intake of abortive medication reduced tear fluid CGRP levels significantly more than spontaneous headache improvement.

Graphical abstract