Hypoxic mechanisms in primary headaches

Abstract

Background Hypoxia causes secondary headaches such as high-altitude headache (HAH) and headache due to acute mountain sickness. These secondary headaches mimic primary headaches such as migraine, which suggests a common link. We review and discuss the possible role of hypoxia in migraine and cluster headache. Methods This narrative review investigates the current level of knowledge on the relation of hypoxia in migraine and cluster headache based on epidemiological and experimental studies. Findings Epidemiological studies suggest that living in high-altitude areas increases the risk of migraine and especially migraine with aura. Human provocation models show that hypoxia provokes migraine with and without aura, whereas cluster headache has not been reliably induced by hypoxia. Possible pathophysiological mechanisms include hypoxia-induced release of nitric oxide and calcitonin gene-related peptide, cortical spreading depression and leakage of the blood-brain barrier. Conclusion There is a possible link between hypoxia and migraine and maybe cluster headache, but the exact mechanism is currently unknown. Provocation models of hypoxia have yielded interesting results suggesting a novel approach to study in depth the mechanism underlying hypoxia and primary headaches.

Migraine associated with altitude: results from a population‐based study in Nepal

“…Britze et al . recently discussed hypoxic mechanisms that might be involved in migraine pathophysiology, but we are inclined to discount these as being relevant since high‐altitude dwellers are fully adapted in order to maintain adequate tissue oxygenation. Finally, cerebral blood flow appears also not to be a relevant factor.…”

“…High-altitude headache is a well-known consequence of rapid ascent to high altitude above 2500 m, whereas the associations between altitude and migraine were strongest below 2500 m [12] and occurred in people chronically exposed to high altitude. Britze et al [17] recently discussed hypoxic mechanisms that might be involved in migraine pathophysiology, but we are inclined to discount these as being relevant since high-altitude Figure 2 Box-plot of migraine attack frequency by altitude. Asterisks denote 'extreme values'; that is, values that are more than three box lengths from either end of the box.…”

Headache in Children: Selected Factors of Vascular Changes Involved in Underlying Processes of Idiopathic Headaches

“…Hypoxia is one of the mechanisms related to migraine. Enhanced expression of PAI-1 may be caused by arterial oxygen desaturation, followed by decreased expression of plasminogen activators, which cause blood hypercoagulability and paradoxical microembolism [ 29 , 110 , 111 ].…”

Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc‐HMPAO Brain SPECT Study

“…Although we cannot completely rule out hypoxia as a primary cause of stroke, accumulating evidence suggests that migraine‐related hyperexcitability may sensitize brain tissue to ischemic damage, so that the migraineurs’ brain is more prone to ischemia, resulting in a higher rate of CSD and brain infarction occurring after mild hypoxia . Not only is hypoxia a well‐known trigger factor for aura, but in mice with CACNA1 gene mutation, even mild hypoxia can readily prompt a cerebral infarction, and the expansion of the core infarct is far more rapid than in wild‐type mice . Therefore, we propose that hypoxia subsequent to bouts of coughing facilitated the occurrence of CSD and, due to its extended length, also migrainous infarction.…”