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The Special Case of High-Altitude Headache

  • Diletta Barbiani
  • Eleonora Camerone
  • Fabrizio BenedettiEmail author
Chapter
Part of the Headache book series (HEAD)

Abstract

Placebo responses have been widely studied in the clinical context and across a variety of different systems. Recent research has shown that placebos and nocebos induce powerful psychological effects that can change the physiology of different body functions and that these changes follow very similar pathways as those induced by drugs. For example, placebo and nocebo effects have been shown to affect both the clinical symptoms and the related biochemical and physiological changes of high-altitude hypoxia headache, where positive or negative expectations lead to the suppression or enhancement of the cyclooxygenase (COX)-prostaglandin (PG) pathway which, in turn, induces pain amelioration or worsening, respectively. High-altitude headache is one of the core neurological hallmarks of the acute mountain sickness (AMS) syndrome and is associated with the ascent to high altitudes and the concomitant drop in atmospheric oxygen pressure. Cellular hypoxia due to reduced barometric pressure seems to be the common final pathway for headache as altitude increases. Within this context, the high-altitude or hypobaric hypoxia headache model represents an extremely valuable opportunity to investigate placebo effects at high altitude, as it represents a borderline condition between the clinical and the experimental setting and allows to induce a clinical condition by bringing healthy subjects from a region of high oxygen pressure (sea level, 159 mmHg) to a region of lower oxygen pressure (high altitude, e.g., 3500 m, 102 mmHg), ruling out ethical constraints. Interestingly, placebo and nocebo research relying on the hypoxia headache model has shown how positive or negative psychosocial cues represent crucial triggers for the decrease and increase in perceived headache and salivary COX products, respectively, suggesting how placebo and nocebo responses are in all respects both psychological and biological phenomena.

Keywords

Hypoxia Oxygen Headache High altitude Placebo Nocebo 

References

  1. 1.
    Bartsch P, Baumgartner RW, Waber U, Maggiorini M, Oelz O. Comparison of carbondioxide-enriched, oxygen-enriched, and normal air in treatment of acute mountain sickness. Lancet. 1990;336:772–5.CrossRefGoogle Scholar
  2. 2.
    Benedetti F. Perspective placebo effects: from the neurobiological paradigm to translational implications. Neuron. 2014;84:623–37.CrossRefGoogle Scholar
  3. 3.
    Benedetti F, Dogue S. Different placebos, different mechanisms, different outcomes: lessons for clinical trials. PLoS One. 2015;10(11):e0140967.CrossRefGoogle Scholar
  4. 4.
    Benedetti F, Durando J, Giudetti L, Pampallona A, Vighetti S. High altitude headache: the effects of real versus sham oxygen administration. Pain. 2015;156:2326–36.CrossRefGoogle Scholar
  5. 5.
    Benedetti F, Durando J, Vighetti S. Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase-prostaglandins pathway. Pain. 2014;155(5):921–8.CrossRefGoogle Scholar
  6. 6.
    Burtscher M, Likar R, Nachbauer W, Philadelphy M. Aspirin for prophylaxis against headache at high altitudes: randomised, double blind, placebo controlled trial. Br Med J. 1998;316:1057–8.CrossRefGoogle Scholar
  7. 7.
    Busse R, Fosterman U, Matsuda H, Pohl U. The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia. Pflugers Arch. 1984;401:77–83.CrossRefGoogle Scholar
  8. 8.
    Davis RJ, Murdoch CE, Ali M, Purbrick S, Ravid R, Baxter GS, et al. EP4 prostanoid receptor-mediated vasodilation of human middle cerebral arteries. Br J Pharmacol. 2004;141:580–5.CrossRefGoogle Scholar
  9. 9.
    Fredericks KT, Liu Y, Rusch NJ, Lombard JH. Role of endothelium and arterial K+ channels in mediating hypoxic dilation of middle cerebral arteries. Am J Physiol. 1994;267:H580–6.Google Scholar
  10. 10.
    Imray C, Wright A, Subudhi A, Roach R. Acute mountain sickness: pathophysiology, prevention and treatment. Prog Cardiovasc Dis. 2010;52:467–84.CrossRefGoogle Scholar
  11. 11.
    International Society for Mountain Medicine. Non-Physician Altitude Tutorial. 2005. Archived from the original on 2011-06-06. Retrieved 22 Dec 2005.Google Scholar
  12. 12.
    Kawabata A. Prostaglandin E2 and pain—an update. Biol Pharm Bull. 2011;34:1170–3.CrossRefGoogle Scholar
  13. 13.
    Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. J Appl Physiol. 2007;102(1):313–22.Google Scholar
  14. 14.
    Marmura MJ, Hernandez PB. High-altitude headache. Curr Pain Headache Rep. 2015;19(5):483.CrossRefGoogle Scholar
  15. 15.
    Messina EJ, Sun D, Koller A, Wolin MS, Kaley G. Role of endothelium-derived prostaglandins in hypoxia elicited arteriolar dilation in rat skeletal muscle. Circ Res. 1992;71:790–6.CrossRefGoogle Scholar
  16. 16.
    Porcelli MJ, Gugelchuk GM. A trek to the top: a review of acute mountain sickness. J Am Osteopath Assoc. 1995;95:718–20.CrossRefGoogle Scholar
  17. 17.
    Ray CJ, Abbas MR, Coney AM, Marshall JM. Interactions of adenosine, prostaglandins and nitric oxide in hypoxia-induced vasodilatation: in vivo and in nitro studies. J Physiol. 2002;544:195–209.CrossRefGoogle Scholar
  18. 18.
    Richalet JP, Hornych A, Rathat C, Aumont J, Larmignat P, Rémy P. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol. 1991;85:205–15.CrossRefGoogle Scholar
  19. 19.
    Sutton JR, Coates G, Houston CS, Oelz O. The Lake Louise consensus on the definition and quantification of altitude illness. In: Sutton JR, Coates G, Houston CS, editors. Hypoxia and mountain medicine. Burlington: Queen City Printers; 1992. p. 327–30.Google Scholar
  20. 20.
    West JB. The physiologic basis of high-altitude diseases. Ann Intern Med. 2004;141:789–800.CrossRefGoogle Scholar
  21. 21.
    Wilson MH, Newman S, Imray CS. The cerebral effects of ascent to high altitudes. Lancet Neurol. 2009;8:175–91.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Diletta Barbiani
    • 1
    • 2
    • 3
  • Eleonora Camerone
    • 4
  • Fabrizio Benedetti
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of NeuroscienceUniversity of Turin Medical SchoolTurinItaly
  2. 2.Plateau Rosà LaboratoriesPlateau RosàBreuil-CerviniaItaly
  3. 3.Plateau Rosà LaboratoriesPlateau RosàZermattSwitzerland
  4. 4.Department of NeuroscienceUniversity of GenoaGenoaItaly

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