Short Report of Longitudinal CGRP-Measurements in Migraineurs During a Hypoxic Challenge

Abstract

BackgroundCalcitonin gene related peptide (CGRP) plays a key role in the pathophysiology of migraine and is therefore considered a potential biomarker for primary headache disorders. The challenge remaining is establishing standardized protocols for its assessment in various extracellular compartments and identifying pathological situations associated with an increase in CGRP.MethodsWe performed longitudinal measurements of CGRP plasma levels in 30 volunteers with the diagnosis of episodic migraine with and without aura under controlled circumstances during an induced migraine attack under a hypoxic challenge. Blood samples were collected from a cubital vein and CGRP plasma levels measured using ELISA.ResultsCGRP levels varied significantly between the subjects at baseline (15.48–1,889.31 pg/ml) but were neither associated with socio-demographic data nor with headache/migraine frequency or intensity collected before hypoxic exposure. CGRP levels during hypoxia fluctuated around baseline and increased with prolonged hypoxia but did not differ significantly in subjects with migraine or headache compared to those without. However, subjects experiencing migraine without aura showed significantly higher levels than those with aura. Ictal CGRP levels were increased in females, in subjects with a negative family history regarding headaches, in those older than 30 years of age or with a recent headache attack before the experiment (p < 0.05).ConclusionCGRP plasma levels seem to be highly variable even at baseline in migraine patients and increased during hypoxic challenge and migraine attacks. This is the first in human longitudinal measurement of peripheral CGRP levels during induced migraine attacks using a highly standardized protocol.

Hypoxia-related mechanisms inducing acute mountain sickness and migraine

“…Using this standardized ELISA based approach, in a longitudinal measurement of CGRP during a normobaric hypoxic challenge in migraine patients, we found elevated CGRP levels with increasing duration of the hypoxic challenge ( Frank et al, 2022 in press).…”

Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat

“…Increased CGRP expression in the TG was not persistent in tongue neuropathic pain models [ 21 , 34 ]. Prolonged hypoxia was sufficient to increase CGRP plasma levels in patients with migraine [ 18 ]. Therefore, it can be inferred that hypoxia has a substantial impact on CGRP upregulation in the TG.…”

“…Recent studies have indicated that oral appliance treatment for OSA may be beneficial for treating headaches in patients with OSA [ 15 ], whereas hypoxia can trigger migraine-like headaches in patients and healthy individuals [ 16 ]. Calcitonin gene-related peptide (CGRP) levels in venous blood, but not substance P, are elevated during acute migraine attacks [ 17 ] and after hypoxic challenge, akin to migraine attacks [ 18 ]. The density of CGRP-positive fibers innervating the oral mucosa is increased in patients with OSA [ 19 ], which suggests that CGRP is a critical factor causing orofacial pain in OSA-like conditions.…”

Kopfschmerzen und Sport

“…Bei 2 Patienten war es die erste Aura überhaupt [47]. Bei diesen Patienten wurden die venösen Calcitonin Gene-Related Peptide (CGRP)-Spiegel vor und nach einer 6-stündigen normobaren Hypoxie (Sauerstoffpartialdruck 4500 m Seehöhe) [48] bestimmt. Im Gruppenmittel stiegen die CGRP-Spiegel im Verlauf der Hypoxie an, wobei eine große interindividuelle Streuung bestand.…”