PAIN
Volume 114, Issue 1 , Pages 3-6 , March 2005

Mechanisms of the placebo response and their impact on clinical trials and clinical practice

  • Damien G. Finniss

      Affiliations

    • Pain Management Research Institute, University of Sydney and Royal North Shore Hospital, Pacific Highway, St Leonards, 2065 Sydney, NSW, Australia
    • Corresponding Author InformationCorresponding author. Tel.: +61 294607095.
  • ,
  • Fabrizio Benedetti

      Affiliations

    • Department of Neuroscience, Clinical and Applied Physiology Program, University of Turin Medical School, Turin, Italy

Received 30 November 2004 ,Accepted 6 December 2004.

References 

  1. Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 1999;19:484–494
  2. Amanzio M, Pollo A, Maggi G, Benedetti F. Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain. 2001;90:205–215
  3. Bausell RB, Lao L, Bergman S, Lee W-L, Berman BM. Is acupuncture analgesia an expectancy effect? Preliminary evidence based upon participants' perceived assignments in two placebo controlled trials. Eval Health Prof 2005; in press.
  4. Benedetti F. How the doctor's words affect the patient's brain. Eval Health Prof. 2002;25:369–386
  5. Benedetti F, Amanzio M, Maggi G. Potentiation of placebo analgesia by proglumide. Lancet. 1995;346:1231
  6. Benedetti F, Amanzio M, Casadio C, Oliaro A, Maggi G. Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain. 1997;71:135–140
  7. Benedetti F, Amanzio M, Baldi S, Casadio C, Maggi G. Inducing placebo respiratory depressant responses in humans via opioid receptors. Eur J Neurosci. 1999;11:625–631
  8. Benedetti F, Arduino C, Amanzio M. Somatotopic activation of opioid systems by target-directed expectations of analgesia. J Neurosci. 1999;19:3639–3648
  9. Benedetti F, Maggi G, Lopiano L, Lanotte M, Rainero I, Vighetti S, et al. Open versus hidden medical treatments: the patient's knowledge about a therapy affects the therapy outcome. Prev Treat. 2003;http://journals.apa.org/prevention/volume6/toc-jun-03.html
  10. Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci. 2003;23:4315–4323
  11. Benedetti F, Colloca L, Torre E, Lanotte M, Melcarne A, Pesare M, et al. Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus. Nat Neurosci. 2004;7:587–588
  12. Colloca L, Lopiano L, Lanotte M, Benedetti F. Overt versus covert treatment for pain, anxiety, and Parkinson's disease. Lancet Neurol. 2004;3:679–684
  13. de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science. 2001;293:1164–1166
  14. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context effects on health outcomes: a systematic review. Lancet. 2001;357:757–762
  15. Gracely RH, Dubner R, Wolskee PJ, Deeter WR. Placebo and naloxone can alter post-surgical pain by separate mechanisms. Nature. 1983;306:264–265
  16. Herrnstein R. Placebo effect in the rat. Science. 1962;138:677–678
  17. Kaptchuk TJ. The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance?. Ann Intern Med. 2002;136:817–825
  18. Kirsch I. Hidden administration as ethical alternatives to the balanced placebo design. Prev Treat. 2003;http://journals.apa.org/prevention/volume6/toc-jun-03.html
  19. Levine JD, Gordon NC. Influence of the method of drug administration on analgesic response. Nature. 1984;312:755–756
  20. Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet. 1978;2:654–657
  21. Lieberman MD, Jarcho JM, Berman S, Naliboff BD, Suyenobu BY, Mandelkern M, et al. The neural correlates of placebo effects: a disruption account. Neuroimage. 2004;22:447–455
  22. McRae C, Cherin E, Yamazaki G, Diem G, Vo AH, Russell D, et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry. 2004;61:412–420
  23. Petrovic P, Kalso E, Petersson KM, Ingvar M. Placebo and opioid analgesia—imaging a shared neuronal network. Science. 2002;295:1737–1740
  24. Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G, Benedetti F. Response expectancies in placebo analgesia and their clinical relevance. Pain. 2001;93:77–84
  25. Price DD. Assessing placebo effects without placebo groups: an untapped possibility?. Pain. 2001;90:201–203
  26. Price DD, Milling LS, Kirsch I, Duff A, Montgomery GH, Nicholls SS. An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm. Pain. 1999;83:147–156
  27. Siegel S. Explanatory mechanisms for placebo effects: Pavlovian conditioning. In:  Guess HA,  Kleinman A,  Kusek JW,  Engel LW editor. The science of the placebo: toward an interdisciplinary research agenda. London: BMJ Books; 2002;p. 133–157
  28. Stewart-Williams S, Podd J. The placebo effect: dissolving the expectancy versus conditioning debate. Psychol Bull. 2004;130:324–340
  29. Stoessl AJ, de la Fuente-Fernandez R. Willing oneself better on placebo-effective in its own right. Lancet. 2004;364:227–228
  30. Vase L, Riley JL, Price DD. A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain. 2002;99:443–452
  31. Volkow ND, Wang G, Ma Y, Fowler JS, Zhu W, Maynard L, et al. Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers. J Neurosci. 2003;23:11461–11468
  32. Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, et al. Placebo-induced changes in fMRI in the anticipation and experience of pain. Science. 2004;303:1162–1166
  33. World Medical Association . Declaration of helsinki. Amended by the 52nd WMA general assembly. J Am Med Assoc. 2000;284:3043–3045
  34. World Medical Association, Note of Clarification on Paragraph 29, Washington; 2002, http://www.wma.net/e/policy/b3.htm

PII: S0304-3959(04)00582-2

doi: 10.1016/j.pain.2004.12.012

PAIN
Volume 114, Issue 1 , Pages 3-6 , March 2005