Tear Fluid Calcitonin Gene-Related Peptide Levels Are Elevated in Glycerol Trinitrate-Induced Cluster Headache Attacks: Results From an Exploratory Study.

BACKGROUND: Cluster headache (CH) is a primary headache disorder characterized by severe, unilateral headache attacks accompanied by trigemino-autonomic symptoms. Calcitonin gene-related peptide (CGRP) is thought to be released during CH attacks, although the role of CGRP has been questioned. In this exploratory study, we investigated tear fluid CGRP levels during experimentally induced CH attacks using glycerol trinitrate. METHODS: Active episodic and chronic CH patients were screened at study Day 1 and eligible patients received sublingual glycerol trinitrate 0.9 mg at study Day 2. Headache characteristics and tear fluid were sampled before and after intake of GTN. Tear fluid CGRP levels were analyzed using a commercial CGRP ELISA (Cusabio, Wuhan, China). RESULTS: 89 episodic (eCH) and chronic cluster headache (cCH) patients were screened. Of these, 18 CH patients (eCH n = 11, 42.6 ± 10.0 years) were included in the analysis. Of 16 CH patients reported an experimentally induced CH attack, tear fluid CGRP levels significantly increased from "baseline" to "headache" ("baseline": 2.34 ± 3.22 ng/mL, "headache": 3.70 ± 5.60 ng/mL; p = 0.019). Tear fluid CGRP levels increased significantly more in participants with an intense headache attack (NRS ≥ 5: +2.65 ± 3.51 ng/mL) compared to participants with a mild intensity (NRS < 5: +0.07 ± 0.83 ng/mL, p = 0.015). CONCLUSION: Our study results support the role of CGRP in the pathophysiology of CH. Further studies with a larger study sample and investigation of other neuropeptides are needed to better understand the underlying mechanisms.