The Role of Calcitonin Gene-Related Peptide in High-Altitude Headache: A Prospective Field Study

High-altitude headache (HAH) is a common neurological condition associated with rapid ascent to high altitude. The pathophysiological mechanisms underlying HAH remain incompletely understood. Calcitonin gene-related peptide (CGRP), a neuropeptide implicated in migraine pathophysiology, may play a key role in the pathophysiology of the disorder due to the shared clinical presentation of migraine and HAH. This study investigated tear fluid CGRP concentrations in response to high-altitude exposure and headache in healthy volunteers.

A prospective field study was conducted during a high-altitude trekking expedition in the Alps. Headache and accompanying symptoms were raised using a structured questionnaire, and tear fluid samples were collected at study Day 1 (baseline, 450 m), at study Day 3 (3647 m), and at study Day 4 (4554 m). Tear fluid CGRP concentrations were quantified using a commercial ELISA kit.

Thirteen participants were included in the analysis. At 4554 m, 61.5% of participants reported a HAH. In participants with HAH, increase of tear fluid CGRP was significantly higher compared to participants without HAH (HAH: +1.49 ± 1.74 ng/mL, no HAH: -0.42 ± 0.64 ng/mL; p = 0.011). Increase of tear fluid CGRP levels was significantly higher in participants with a moderate-to-severe headache (+1.86 ± 1.86 ng/mL) compared to participants with mild headache (-0.19 ± 0.75 ng/mL; p = 0.008).

The results support a potential role for CGRP in the pathophysiology of HAH. Further studies with a larger number of participants are needed to determine the mechanisms of the disorder.