title: Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes.
abstract: Head-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.
authors.affiliation: Department of Anaesthesiology, Klinikum Großhadern, University of Munich, Munich, Germany Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Feuerecker
authors.forename: Willebrordus P J
authors.initials: WPJ
authors.lastname: van Oosterhout
authors.forename: Benedikt
authors.initials: B
authors.lastname: Feuerecker
authors.forename: Sandra
authors.initials: S
authors.lastname: Matzel
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.forename: Markus
authors.initials: M
authors.lastname: Rehm
authors.forename: Alla A
authors.initials: AA
authors.lastname: Vein
authors.forename: Alexander
authors.initials: A
authors.lastname: Choukèr
mesh_terms: D000328:Adult; D002772:Cholera Toxin / Q000378:metabolism; D018592:Cross-Over Studies; D004326:Drinking; D004727:Endothelium / Q000378:metabolism; D004837:Epinephrine / Q000652:urine; D004906:Erythrocyte Count; D019276:Glycocalyx / Q000378:metabolism; D006242:Haptoglobins; D018475:Head-Down Tilt; D006261:Headache / Q000378:metabolism* / Q000473:pathology*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement; D011498:Protein Precursors; D012463:Saliva; D019108:Tight Junctions / Q000473:pathology*; D014893:Weightlessness; D018474:Weightlessness Simulation; D055815:Young Adult
chemical_list: D006242:Haptoglobins; D006454:Hemoglobins; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin; D006854:Hydrocortisone; D004837:Epinephrine