What is the relative contribution of biological and psychosocial factors to the generation of hypoxia headache?

Background: The biopsychosocial model claims that illness is generated by both biological and psychosocial factors. Accordingly, several studies have shown that both factors contribute to the generation of pain. Aims: The aim of the present study is to manipulate biological, psychological, and social factors in hypobaric hypoxia headache in order to understand their relative contribution to the generation of headache pain. Methods: Healthy subjects were subdivided into three groups and brought to our high-altitude labs for the assessment of hypoxia-induced headache, blood oxygen saturation (SO2), prostaglandins, and cortisol during the first 24 h after arrival. The first group did not undergo any manipulation. The second group (negative expectation) was told that severe headache would occur if SO2 dropped to less than 80% and their oximeters were set to display a saturation of 75%, even though real SO2 was much higher. The third group (negative expectation and social interaction) underwent the same manipulation as the second group, but these subjects spent the night together with people experiencing headache and insomnia. Results: Although none of the three groups differed significantly for SO2, the second group, compared to the first, experienced more severe headache and showed an increase in prostaglandins and cortisol. The third group, compared to the second group, showed a further increase of headache as well as of prostaglandin (PG) E2 and cortisol. Conclusions: These findings indicate that biological, psychological, and social factors are additive not only in the generation of headache but also for the biochemical changes related to hypoxia.