High-altitude headache

the effects of real vs sham oxygen administration

Abstract

High-altitude, or hypobaric hypoxia, headache has recently emerged as an interesting model to study placebo and nocebo responses, and particularly their peripheral mechanisms. In this study, we analyze the response of this type of headache to either real or sham (placebo) oxygen (O₂) administration at an altitude of 3500 m, where blood oxygen saturation (SO₂) drops from the normal value of about 98% to about 85%. In a trial in which a double-blind administration of either 100% O₂ or sham O₂ was administered, we tested pre- and post-exercise headache, along with fatigue, heart rate (HR) responses, and prostaglandin E₂ (PGE₂) salivary concentration. Although real O₂ breathing increased SO₂ along with a decrease in pre- and post-exercise headache, fatigue, HR, and PGE₂, placebo O₂ changed neither pre-/post-exercise headache nor SO₂/HR/PGE₂, but it decreased fatigue. However, in another group of subjects, when sham O₂ was delivered after 2 previous exposures to O₂ (O₂ preconditioning), it decreased fatigue, post-exercise headache, HR, and PGE₂, yet without any increase in SO₂. Three main findings emerge from these data. First, placebo O₂ is effective in reducing post-exercise headache, along with HR and PGE₂ decrease, only after O₂ preconditioning. Second, pre-exercise (at rest) headache is not affected by placebo O₂, which emphasizes the limits of a placebo treatment at high altitude. Third, fatigue is affected by placebo O₂ even without prior O₂ conditioning, which suggests the higher placebo sensitivity of fatigue compared with headache pain at high altitude.

In Brief

Sham (placebo) oxygen reduces high-altitude headache and prostaglandin E₂ only after oxygen preconditioning, highlighting the important role of learning in placebo analgesia.