Migraine and aura triggered by normobaric hypoxia

Abstract

Background For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. Methods To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO2 of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. Findings Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO2 during hypoxia was 83.39%. Conclusion Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.

The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack

“…It has been shown that exposure of migraine subjects to normobaric hypoxia can trigger both the migraine attacks and the manifestations of the aura [29]. These findings have been replicated in a recent study [30] in which aura occurred for the first time under experimental hypoxic conditions also in two migraine without aura volunteers. These studies agree in considering hypoxia a powerful trigger of migraine attack with or without aura.…”

Cortical spreading depression and meningeal nociception

“…The mechanisms responsible for these metabolic responses are likely numerous, although the release of cyclooxygenase (COX)-derived vasoconstricting prostanoids and other eicosanoid metabolites of arachidonic acid plays a key role ( Fordsmann et al, 2013 , Gariepy et al, 2017 , Shibata et al, 1992 ). Reduced blood flow and tissue oxygenation can trigger a migraine attack in susceptible individuals ( Appenzeller, 1994 , Arngrim et al, 2016 , Broessner et al, 2016 , Frank et al, 2020 , Schoonman et al, 2006 ). These findings, together with the notion that reduced blood flow and tissue oxygenation lead to the sensitization of nociceptors in other tissues ( Hillery et al, 2011 , MacIver and Tanelian, 1992 , Mense and Stahnke, 1983 ), raises the possibility that the mechanisms responsible for driving dural nociceptors in the wake of CSD involve similar vascular and metabolic changes.…”

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

“…These include higher prevalence of migraines in elevated regions ( 9 , 10 ) oxidative stress as mechanism for migraine triggers ( 11 ), detection of tissue hypoxia during cortical spreading depression ( 12 ) and, foremost, safe and successful induction of migraine headache in experimental settings utilizing hypoxia ( 13 ). The hypoxic challenge performed in this study has been described in an earlier publication of our group ( 14 ).…”