• Matthias Feuerecker, Willebrordus P J van Oosterhout, Benedikt Feuerecker, Sandra Matzel, Gustav Schelling, Markus Rehm, Alla A Vein, and Alexander Choukèr.
• aDepartment of Anaesthesiology, Klinikum Großhadern, University of Munich, Munich, Germany bDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands cDepartment of Nuclear Medicine, Technische Universität München, Munich, Germany.
• Pain. 2016 May 1; 157 (5): 1072-8.

AbstractHead-down-tilted bed rest (HDTBR) induces headaches similar to headaches during space flights. The objective of this investigation was to study hematological, endocrinological, fluid changes and tight junctions in HDTBR-induced headaches as a proxy for space headache. The randomized crossover HDTBR design by the European Space Agency included 12 healthy, nonheadache male subjects. Before, during, and after confined HDTBR periods, epinephrine (urine), cortisol (saliva), hematological, endothelium markers, and fluid distribution parameters were measured. Headaches were assessed with a validated headache questionnaire. Compared with baseline, HDTBR in all subjects was associated with higher hematocrit, hemoglobin, and epinephrine levels, higher erythrocyte counts, and lower relative plasma volumes (all P < 0.05). In total, 26 headache episodes occurred. In subjects with headaches during HDTBR, epinephrine levels were exaggerated (vs headache-free subjects; HDTBR day 3; 5.1 ± 1.7 vs 3.4 ± 2.4; P = 0.023), cortisol levels were decreased (vs headache-free subjects; HDTBR day 1; 0.37 ± 0.16 vs 0.50 ± 0.20; P < 0.001) and the tight junction marker zonulin was elevated (vs headache-free subjects in HDTBR days 1, 3, 5; P < 0.05). HDTBR induces hemoconcentration and fluid redistribution in all subjects. During headache episodes, endocrinological changes, fluid distribution, and tight junctions were more pronounced, suggesting an additional role in headache pathophysiology.

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