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Placebos and Nocebos in Headaches pp 65–74Cite as

Placebo Response in Human Models of Headache

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Part of the book series: Headache ((HEAD))

Abstract

Human models of migraine are important to better understand the underlying mechanisms of action of potential anti-migraine compounds as well as to explore the pathophysiology of the condition. Like in other interventions, participant expectations, content and delivery of information, and unspecific effects of the intervention may exert a placebo or nocebo effect on the outcomes. However, the recorded placebo responses are modest in human studies for migraine. With the use of an appropriate control intervention, this effect may be mitigated and taken into account. In this chapter all human models of migraine are summarized in relation to the placebo response.

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References

  1. Antonova M, Wienecke T, Olesen J, Ashina M. Prostaglandin E(2) induces immediate migraine-like attack in migraine patients without aura. Cephalalgia. 2012;32:822–33.

    Article  Google Scholar 

  2. Arngrim N, Schytz HW, Britze J, Amin FM, Vestergaard MB, Hougaard A, Wolfram F, de Koning PJ, Olsen KS, Secher NH, Larsson HB, Olesen J, Ashina M. Migraine induced by hypoxia: an MRI spectroscopy and angiography study. Brain. 2016;139:723–37.

    Article  Google Scholar 

  3. Asghar MS, Hansen AE, Kapijimpanga T, van der Geest RJ, van der Koning P, Larsson HB, Olesen J, Ashina M. Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers. Neurology. 2010;75:1520–6.

    Article  CAS  Google Scholar 

  4. Ashina M. Human models—screening models. Oxford: Oxford University Press; 2008.

    Book  Google Scholar 

  5. Ashina M, Bendtsen L, Jensen R, Olesen J. Nitric oxide-induced headache in patients with chronic tension-type headache. Brain. 2000;123(Pt 9):1830–7.

    Article  Google Scholar 

  6. Ashina M, Hansen JM, Bo AD, Olesen J. Human models of migraine—short-term pain for long-term gain. Nat Rev Neurol. 2017;13:713–24.

    Article  Google Scholar 

  7. Birk S, Kruuse C, Petersen KA, Tfelt-Hansen P, Olesen J. The headache-inducing effect of cilostazol in human volunteers. Cephalalgia. 2006;26:1304–9.

    Article  CAS  Google Scholar 

  8. Diener HC, Dowson AJ, Ferrari M, Nappi G, Tfelt-Hansen P. Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials. Cephalalgia. 1999;19:699–700.

    Article  CAS  Google Scholar 

  9. Guo S, Olesen J, Ashina M. Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase. Brain. 2014;137:2951–9.

    Article  Google Scholar 

  10. Hansen EK, Olesen J. Towards a pragmatic human migraine model for drug testing: 2. Isosorbide-5-mononitrate in healthy individuals. Cephalalgia. 2017;37(1):11–9.

    Article  Google Scholar 

  11. Hansen JM, Sitarz J, Birk S, Rahmann AM, Oturai PS, Fahrenkrug J, Olesen J, Ashina M. Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers. Cephalalgia. 2006;26:992–1003.

    Article  CAS  Google Scholar 

  12. Hansen JM, Pedersen D, Larsen VA, Sanchez-del-Rio M, Alvarez Linera JR, Olesen J, Ashina M. Magnetic resonance angiography shows dilatation of the middle cerebral artery after infusion of glyceryl trinitrate in healthy volunteers. Cephalalgia. 2007;27:118–27.

    Article  CAS  Google Scholar 

  13. Hrobjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010;(1):CD003974.

    Google Scholar 

  14. IHS. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.

    Article  Google Scholar 

  15. Jensen K, Tfelt-Hansen P, Hansen EW, Krois EH, Pedersen OS. Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice. Cephalalgia. 1995;15:423–9.

    Article  CAS  Google Scholar 

  16. Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med. 2014;6:218ra5.

    Article  Google Scholar 

  17. Kruuse C, Frandsen E, Schifter S, Thomsen LL, Birk S, Olesen J. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache. Cephalalgia. 2004;24:547–53.

    Article  CAS  Google Scholar 

  18. Kruuse C, Thomsen LL, Birk S, Olesen J. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 2003;126:241–7.

    Article  Google Scholar 

  19. Kruuse C, Thomsen LL, Jacobsen TB, Olesen J. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects. J Cereb Blood Flow Metab. 2002;22:1124–31.

    Article  CAS  Google Scholar 

  20. Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia. 2002;22:54–61.

    Article  CAS  Google Scholar 

  21. Loder E, Goldstein R, Biondi D. Placebo effects in oral triptan trials: the scientific and ethical rationale for continued use of placebo controls. Cephalalgia. 2005;25:124–31.

    Article  CAS  Google Scholar 

  22. Macedo A, Farre M, Banos JE. A meta-analysis of the placebo response in acute migraine and how this response may be influenced by some of the characteristics of clinical trials. Eur J Clin Pharmacol. 2006;62:161–72.

    Article  Google Scholar 

  23. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabe E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2197–223.

    Article  Google Scholar 

  24. Nichols FT 3rd, Mawad M, Mohr JP, Stein B, Hilal S, Michelsen WJ. Focal headache during balloon inflation in the internal carotid and middle cerebral arteries. Stroke. 1990;21:555–9.

    Article  Google Scholar 

  25. Olesen J, Tfelt-Hansen P, Ashina M. Finding new drug targets for the treatment of migraine attacks. Cephalalgia. 2009;29:909–20.

    Article  CAS  Google Scholar 

  26. Perrotta A, Serrao M, Tassorelli C, Arce-Leal N, Guaschino E, Sances G, Rossi P, Bartolo M, Pierelli F, Sandrini G, Nappi G. Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: a double-blind, placebo-controlled, cross-over study. Eur J Pain. 2011;15:482–90.

    Article  CAS  Google Scholar 

  27. Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia. 2008;28:226–36.

    Article  CAS  Google Scholar 

  28. Russell MB, Rasmussen BK, Brennum J, Iversen HK, Jensen RA, Olesen J. Presentation of a new instrument: the diagnostic headache diary. Cephalalgia. 1992;12:369–74.

    Article  CAS  Google Scholar 

  29. Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain. 2009;132:16–25.

    Article  Google Scholar 

  30. Schytz HW, Wienecke T, Olesen J, Ashina M. Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura. Cephalalgia. 2010;30:337–45.

    Article  CAS  Google Scholar 

  31. Schytz HW, Wienecke T, Oturai PS, Olesen J, Ashina M. The cholinomimetic agent carbachol induces headache in healthy subjects. Cephalalgia. 2009;29:258–68.

    Article  CAS  Google Scholar 

  32. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1545–602.

    Google Scholar 

  33. Thomsen LL, Iversen HK, Brinck TA, Olesen J. Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers. Cephalalgia. 1993;13:395–9; discussion 376.

    Article  CAS  Google Scholar 

  34. Thomsen LL, Kruuse C, Iversen HK, Olesen J. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks. Eur J Neurol. 1994;1:73–80.

    Article  CAS  Google Scholar 

  35. Tvedskov JF, Thomsen LL, Iversen HK, Gibson A, Wiliams P, Olesen J. The prophylactic effect of valproate on glyceryltrinitrate induced migraine. Cephalalgia. 2004;24:576–85.

    Article  CAS  Google Scholar 

  36. Tvedskov JF, Thomsen LL, Iversen HK, Williams P, Gibson A, Jenkins K, Peck R, Olesen J. The effect of propranolol on glyceryltrinitrate-induced headache and arterial response. Cephalalgia. 2004;24:1076–87.

    Article  CAS  Google Scholar 

  37. Wienecke T, Olesen J, Ashina M. Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia. 2010;30:179–90.

    Article  CAS  Google Scholar 

  38. Wienecke T, Olesen J, Oturai PS, Ashina M. Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain. 2008;139:106–16.

    Article  CAS  Google Scholar 

  39. Wienecke T, Olesen J, Oturai PS, Ashina M. Prostaglandin E2(PGE2) induces headache in healthy subjects. Cephalalgia. 2009;29:509–19.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Danish Headache Center, Rigshospitalet, Glostrup, Denmark

    Jakob Møller Hansen & Messoud Ashina

  2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Jakob Møller Hansen & Messoud Ashina

Authors
  1. Jakob Møller Hansen
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  2. Messoud Ashina
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Corresponding author

Correspondence to Messoud Ashina .

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Editors and Affiliations

  1. Neurology Department, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Dimos D. Mitsikostas

  2. Neuroscience Department, University of Turin Medical School, Torino, Italy

    Fabrizio Benedetti

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Hansen, J.M., Ashina, M. (2019). Placebo Response in Human Models of Headache. In: Mitsikostas, D., Benedetti, F. (eds) Placebos and Nocebos in Headaches. Headache. Springer, Cham. https://doi.org/10.1007/978-3-030-02976-0_6

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  • DOI: https://doi.org/10.1007/978-3-030-02976-0_6

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-02975-3

  • Online ISBN: 978-3-030-02976-0

  • eBook Packages: MedicineMedicine (R0)

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