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Placebo pp 139–147Cite as

Great Expectations: The Placebo Effect in Parkinson’s Disease

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 225))

Abstract

Our understanding of the neural mechanisms underlying the placebo effect has increased exponentially in parallel with the advances in brain imaging. This is of particular importance in the field of Parkinson’s disease, where clinicians have described placebo effects in their patients for decades. Significant placebo effects have been observed in clinical trials for medications as well as more invasive surgical trials including deep-brain stimulation and stem-cell implantation. In addition to placebo effects occurring as a byproduct of randomized controlled trials, investigation of the placebo effect itself in the laboratory setting has further shown the capacity for strong placebo effects within this patient population. Neuroimaging studies have demonstrated that placebos stimulate the release of dopamine in the striatum of patients with Parkinson’s disease and can alter the activity of dopamine neurons using single-cell recording. When taken together with the findings from other medical conditions discussed elsewhere in this publication, a unified mechanism for the placebo effect in Parkinson’s disease is emerging that blends expectation-induced neurochemical changes and disease-specific nigrostriatal dopamine release.

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References

  • Benedetti F (2010) No prefrontal control, no placebo response. Pain 148(3):357–358

    Article  PubMed  Google Scholar 

  • Benedetti F (2012) Placebo-induced improvements: how therapeutic rituals affect the patient’s brain. J Acupunct Meridian Stud 5(3):97–103

    Article  PubMed  Google Scholar 

  • Benedetti F (2013) Placebo and the new physiology of the doctor-patient relationship. Physiol Rev 93(3):1207–1246

    Article  PubMed  PubMed Central  Google Scholar 

  • Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I (2003) Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 23(10):4315–4323

    PubMed  CAS  Google Scholar 

  • Benedetti F, Colloca L, Torre E, Lanotte M, Melcarne A, Pesare M, Bergamasco B, Lopiano L (2004) Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nat Neurosci 7(6):587–588

    Article  PubMed  CAS  Google Scholar 

  • Benedetti F, Arduino C, Costa S, Vighetti S, Tarenzi L, Rainero I, Asteggiano G (2006) Loss of expectation-related mechanisms in Alzheimer’s disease makes analgesic therapies less effective. Pain 121(1–2):133–144

    Article  PubMed  CAS  Google Scholar 

  • Bishop MP, Elder ST, Heath RG (1963) Intracranial self-stimulation in man. Science 140:394–396

    Article  PubMed  CAS  Google Scholar 

  • Breiter HC, Rosen BR (1999) Functional magnetic resonance imaging of brain reward circuitry in the human. Ann N Y Acad Sci 877:523–547

    Article  PubMed  CAS  Google Scholar 

  • Calne SM, Lidstone SC, Kumar A (2008) Psychosocial issues in young-onset Parkinson’s disease: current research and challenges. Parkinsonism Relat Disord 14(2):143–150

    Article  PubMed  Google Scholar 

  • Colloca L, Lopiano L, Lanotte M, Benedetti F (2004) Overt versus covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurol 3(11):679–684

    Article  PubMed  Google Scholar 

  • de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ (2001) Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease. Science 293(5532):1164–1166

    Article  PubMed  Google Scholar 

  • de la Fuente-Fernandez R, Phillips AG, Zamburlini M, Sossi V, Calne DB, Ruth TJ, Stoessl AJ (2002) Dopamine release in human ventral striatum and expectation of reward. Behav Brain Res 136(2):359–363

    Article  PubMed  Google Scholar 

  • de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2004) Placebo mechanisms and reward circuitry: clues from Parkinson’s disease. Biol Psychiatry 56(2):67–71

    Article  PubMed  Google Scholar 

  • Diamond SG, Markham CH, Treciokas LJ (1985) Double-blind trial of pergolide for Parkinson’s disease. Neurology 35(3):291–295

    Article  PubMed  CAS  Google Scholar 

  • Dreher JC, Kohn P, Berman KF (2006) Neural coding of distinct statistical properties of reward information in humans. Cereb Cortex 16:561–573

    Article  PubMed  Google Scholar 

  • Fiorillo CD, Tobler PN, Schultz W (2003) Discrete coding of reward probability and uncertainty by dopamine neurons. Science 299(5614):1898–1902

    Article  PubMed  CAS  Google Scholar 

  • Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344(10):710–719

    Article  PubMed  CAS  Google Scholar 

  • Goetz CG, Leurgans S, Raman R (2002a) Objective changes in motor function during placebo treatment in PD. Neurology 54(3):710–714

    Article  Google Scholar 

  • Goetz CG, Leurgans S, Raman R (2002b) Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson’s disease. Mov Disord 12(2):283–288

    Article  Google Scholar 

  • Haber SN, Fudge JL (1997) The primate substantia nigra and VTA: integrative circuitry and function. Crit Rev Neurobiol 11(4):323–342

    Article  PubMed  CAS  Google Scholar 

  • Horvitz JC (2000) Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events. Neuroscience 96:651–656

    Article  PubMed  CAS  Google Scholar 

  • Koepp MJ, Gunn RN, Lawrence AD, Cunningham VJ, Dagher A, Jones T, Brooks DJ, Bench CJ, Grasby PM (1998) Evidence for striatal dopamine release during a video game. Nature 393:266–268

    Article  PubMed  CAS  Google Scholar 

  • Lanotte M, Lopiano L, Torre E, Bergamasco B, Colloca L, Benedetti F (2005) Expectation enhances autonomic responses to stimulation of the human subthalamic limbic region. Brain Behav Immun 19(6):500–509

    Article  PubMed  Google Scholar 

  • Lidstone SC, Stoessl AJ (2007) Understanding the placebo effect: contributions from neuroimaging. Mol Imaging Biol 9(4):176–185

    Article  PubMed  Google Scholar 

  • Lidstone SC, Schulzer M, Dinelle K, Mak E, Sossi V, Ruth TJ, Fuente-Fernandez R, Phillips AG, Stoessl AJ (2010) Effects of expectation on placebo-induced dopamine release in Parkinson disease. Arch Gen Psychiatry 67(8):857–865

    Article  PubMed  CAS  Google Scholar 

  • Ljungberg T, Apicella P, Schultz W (1992) Responses of monkey dopamine neurons during learning of behavioral reactions. J Neurophysiol 67:145–163

    PubMed  CAS  Google Scholar 

  • McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, Dillon S, Winfield H, Bjugstad KB, Freed CR (2004) Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 61(4):412–420

    Article  PubMed  Google Scholar 

  • Mercado R, Constantoyannis C, Mandat T, Kumar A, Schulzer M, Stoessl AJ, Honey CR (2006) Expectation and the placebo effect in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation. Mov Disord 21(9):1457–1461

    Article  PubMed  Google Scholar 

  • Mirenowicz J, Schultz W (1994) Importance of unpredictability for reward responses in primate dopamine neurons. J Neurophysiol 72:1024–1027

    PubMed  CAS  Google Scholar 

  • Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54(3):403–414

    Article  PubMed  Google Scholar 

  • Olds J, Milner P (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol 47:419–427

    Article  PubMed  CAS  Google Scholar 

  • Pollo A, Torre E, Lopiano L, Rizzone M, Lanotte M, Cavanna A, Bergamasco B, Benedetti F (2002) Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients. NeuroReport 13(11):1383–1386

    Article  PubMed  Google Scholar 

  • Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80(1):1–27

    PubMed  CAS  Google Scholar 

  • Schultz W (2000) Multiple reward signals in the brain. Nat Rev Neurosci 1:199–207

    Article  PubMed  CAS  Google Scholar 

  • Schultz W (2001) Reward signaling by dopamine neurons. Neuroscientist 7(4):293–302

    Article  PubMed  CAS  Google Scholar 

  • Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK (2007) Individual differences in reward responding explain placebo-induced expectations and effects. Neuron 55(2):325–336

    Article  PubMed  CAS  Google Scholar 

  • Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK (2008) Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry 65(2):220–231

    Article  PubMed  Google Scholar 

  • Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D (1999) The placebo response in Parkinson’s disease. Parkinson Study Group. Clin Neuropharmacol 22(4):207–212

    PubMed  CAS  Google Scholar 

  • Small DM, Jones-Gotman M, Dagher A (2003) Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. NeuroImage 19:1709–1715

    Article  PubMed  Google Scholar 

  • Strafella AP, Ko JH, Monchi O (2006) Therapeutic application of transcranial magnetic stimulation in Parkinson’s disease: the contribution of expectation. NeuroImage 31(4):1666–1672

    Article  PubMed  PubMed Central  Google Scholar 

  • Tobler PN, Fiorillo CD, Schultz W (2005) Adaptive coding of reward value by dopamine neurons. Science 307(5715):1642–1645

    Article  PubMed  CAS  Google Scholar 

  • Watts RL, Freeman TB, Hauser RA, Bakay RAE, Ellias SA, Stoessl AJ, Eidelberg D, Fink JS (2001) A double-blind, randomised, controlled, multicenter clinical trial of the safety and efficacy of stereotaxic intrastriatal implantation of fetal porcine ventral mesencephalic tissue (NeurocellTM-PD) vs. imitation surgery in patients with Parkinson’s disease (PD). Parkinsonism Relat Disord 7(S87)

    Google Scholar 

  • Zald DH, Boileau I, El Dearedy W, Gunn R, McGlone F, Dichter GS, Dagher A (2004) Dopamine transmission in the human striatum during monetary reward tasks. J Neurosci 24:4105–4112

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Neurology Residency Program, University of Toronto, Toronto, ON, Canada

    Sarah Christine Lidstone

Authors
  1. Sarah Christine Lidstone
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Correspondence to Sarah Christine Lidstone .

Editor information

Editors and Affiliations

  1. Neuroscience Department and National Institute of Neuroscience Labs, University of Turin Medical School, Turin, Italy

    Fabrizio Benedetti

  2. Department of Psychosomatic Medicine, University Hospitals Tuebingen, Tuebingen, Germany

    Paul Enck

  3. Neuroscience Department and National Institute of Neuroscience Labs, University of Turin Medical School, Turin, Italy

    Elisa Frisaldi

  4. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany

    Manfred Schedlowski

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© 2014 Springer-Verlag Berlin Heidelberg

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Lidstone, S.C. (2014). Great Expectations: The Placebo Effect in Parkinson’s Disease. In: Benedetti, F., Enck, P., Frisaldi, E., Schedlowski, M. (eds) Placebo. Handbook of Experimental Pharmacology, vol 225. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44519-8_8

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