Fig 1

Rationale of the study.

High altitude headache can be due to at least two pathways. The first is the reduction of blood oxygen saturation (SO2), which triggers compensatory hyperventilation and excessive elimination of carbon dioxide (CO2) which, in turn, increases blood pH (alkalosis). The importance of alkalosis in high altitude headache is shown by the therapeutic effects of acetazolamide, that reduces blood pH. The second pathway is the activation of cyclooxygenase (COX) by hypoxia with an increase in prostaglandin (PG) synthesis which, in turn, induces cerebral vasodilation. High altitude headache can be treated with oxygen or COX inhibitors, like aspirin, and these treatments require two different therapeutic rituals. In the former, oxygen is breathed through a mask, in the latter, aspirin is a pill that is taken orally. This allows the study of the mechanisms of two different placebos associated to two different rituals.