Advertisement

Pain and the Placebo Effect

  • Antonella Pollo
  • Fabrizio Benedetti
Chapter

Psychological Modulation of Pain

Since ancient times it has been recognized that many psychological factors can strongly influence and modulate the multidimensional experience of pain. Attending a distracting toy can make a distressed child stop crying, and expectation of pain relief can lessen the unpleasantness of stomach-aches. Attention, emotions, suggestions and expectations, anxiety, fear, mood are among the best known examples of factors that can shape the processing of nociceptive information as it travels from the spinal cord to higher centers in the brain.

The understanding of the neurobiological basis of this top-down modulation of pain represents a challenge in pain research and many efforts are currently devoted to the development of models illustrating its “modus operandi”. One such model is offered by placebo analgesia, i.e. the lessening of pain experienced in response to a therapeutic act devoid of intrinsic analgesic activity. As it will be detailed in this chapter,...

Keywords

Irritable Bowel Syndrome Anterior Cingulate Cortex Placebo Effect Irritable Bowel Syndrome Patient Placebo Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ader, R. (1997). The role of conditioning in pharmacotherapy. In: Harrington, A. (Ed.). The placebo effect: An interdisciplinary exploration (pp. 138–165). Cambridge, MA: Harvard University Press.Google Scholar
  2. Ader, R., & Cohen, N. (1982). Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science, 215:1534–1536.CrossRefPubMedGoogle Scholar
  3. Amanzio, M., & Benedetti, F. (1999). Neuropharmacological dissection of placebo analgesia: Expectation-activated 7/26/2008 3:28AMopioid systems versus conditioning-activated specific sub-systems. Journal of Neuroscience, 19:484–494.PubMedGoogle Scholar
  4. Amanzio, M., Pollo, A., Maggi, G., & Benedetti, F. (2001). Response variability and to analgesics: A role for non-specific activation of endogenous opioids. Pain, 90:205–215.CrossRefPubMedGoogle Scholar
  5. Andre, J., Zeau, B., Pohl, M., Cesselin, F., Benoliel, J. J., & Becker, C. (2005). Involvement of cholecystokininergic systems in anxiety-induced hyperalgesia in male rats: behavioural and biochemical studies. Journal of Neuroscience. 25:7896–7904.CrossRefPubMedGoogle Scholar
  6. Bausell, R. B., Lao, L., Bergman, S., Lee, W. L., & Berman, B. M. (2005). Is acupuncture analgesia an expectancy effect? Evaluation and The Health Professions, 215:9–26.Google Scholar
  7. Bencherif, B., Fuchs, P. N., Sheth, R., Dannals, R. F., Campbell, J. N., & Frost, J. J. (2002). Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET). Pain, 215:589–598.CrossRefGoogle Scholar
  8. Benedetti, F. (1996). The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia. Pain, 215:535–543.CrossRefGoogle Scholar
  9. Benedetti, F. (2002). How the doctor’s words affect the patient’s brain. Evaluation and The Health Professions, 215:369–386.Google Scholar
  10. Benedetti, F., Amanzio, M., & Maggi, G. (1995). Potentiation of placebo analgesia by proglumide. Lancet, 215:1231.CrossRefGoogle Scholar
  11. Benedetti, F., Amanzio, M., Casadio, C., Oliaro, A., & Maggi, G. (1997). Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain, 215:135–140.CrossRefGoogle Scholar
  12. Benedetti, F., Arduino, C., & Amanzio, M. (1999a). Somatotopic activation of opioid systems by target-directed expectations of analgesia. Journal of Neuroscience, 215:3639–3648.Google Scholar
  13. Benedetti, F., Amanzio, M., Baldi, S., Casadio, C., & Maggi, G. (1999b). Inducing placebo respiratory depressant responses in humans via opioid receptors. European Journal of Neuroscience, 215:625–631.Google Scholar
  14. Benedetti, F., Maggi, G., Lopiano, L., Lanotte, M., Rainero, I., Vighetti, S., et al. (2003). Open versus hidden medical treatments: The patient’s knowledge about a therapy affects the therapy outcome. Prevention and Treatment. http://content2.apa.org/journals/pre/6/1/1
  15. 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. Journal of Neuroscience, 23:4315–4323.PubMedGoogle Scholar
  16. Benedetti, F., Amanzio, M., Vighetti, S., & Asteggiano, G. (2006) The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. Journal of Neuroscience, 215:12014–12022.CrossRefGoogle Scholar
  17. Benedetti, F., Arduino, C., Costa, S., Vighetti, S., Tarenzi, L., Rainero, I., et al. (2006). Loss of expectation-related mechanisms in Alzheimer’s disease makes analgesic therapies less effective. Pain, 215:133–144.CrossRefGoogle Scholar
  18. Benedetti, F., Lanotte, M., Lopiano, L., & Colloca, L. (2007) When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience, 215:260–271.CrossRefGoogle Scholar
  19. Bingel, U., Lorenz, J., Schoell, E., Weiller, C., & Büchel, C. (2006). Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network. Pain, 215:8–15.CrossRefGoogle Scholar
  20. Brody, H. (2000). The placebo response. New York. Harper Collins.Google Scholar
  21. Charron, J., Rainville, P., & Marchand, S. (2006). Direct comparison of placebo effects on clinical and experimental pain. Clinical Journal of Pain 22:204–211.CrossRefPubMedGoogle Scholar
  22. Colloca, L., & Benedetti, F. (2005). Placebos and painkillers: is mind as real as matter? Nature Reviews Neuroscience, 215:545–552.CrossRefGoogle Scholar
  23. Colloca, L., Lopiano, L., Lanotte, M., & Benedetti, F. (2004). Overt versus covert treatment for pain, anxiety, and Parkinson’s disease. Lancet Neurology,3:679–684.CrossRefPubMedGoogle Scholar
  24. Davis, C. E. (2002). Regression to the mean or placebo effect? In: Guess, H. A., Kleinman, A., Kusek, J. W., & Engel, L. W. (Eds.), The science of the placebo: Toward an interdisciplinary research agenda (pp. 158–166). London: BMJ Books.Google Scholar
  25. Di Blasi, Z., Harkness, E., Ernst, E., Georgiou, A., & Kleijnen, J. (2001). Influence of context effect on health outcomes: A systematic review. Lancet 357:757–762.CrossRefPubMedGoogle Scholar
  26. Dworkin, S. F., Chen, A. C., LeResche, L., & Clark, D. W. (1983). Cognitive reversal of expected nitrous oxide analgesia for acute pain. Anesthesia and Analgesia, 215:1073–1077.Google Scholar
  27. Fields, H. (2004). State-dependent opioid control of pain. Nature Reviews Neuroscience, 215:565–575.CrossRefGoogle Scholar
  28. Fields, H. L., & Levine, J. D. (1984). Placebo analgesia -- a role for endorphins? Trends Neuroscience, 215:271–273.CrossRefGoogle Scholar
  29. Giang, D. W., Goodman, A. D., Schiffer, R. B., Mattson, D. H., Petrie, M., Cohen, N., et al. (1996). Conditioning of cyclophosphamide-induced leukopenia in humans. Journal of Neuropsychiatry and Clinical Neurosciences, 215:194–201.Google Scholar
  30. Goebel, M. U., Trebst, A. E., Steiner, J., Xie, Y. F., Exton, M. S., Frede, S., et al. (2002). Behavioral conditioning of immunosuppression is possible in humans. FASEB Journal, 215:1869–1873.CrossRefGoogle Scholar
  31. Gracely, R. H., Dubner, R., Wolskee, P. J., & Deeter, W. R. (1983). Placebo and naloxone can alter post-surgical pain by separate mechanisms. Nature, 215:264–265.CrossRefGoogle Scholar
  32. Gracely, R. H., Dubner, R., Deeter, W. D., & Wolskee, P. J. (1985). Clinician’s expectations influence placebo analgesia. Lancet, 215:43.CrossRefGoogle Scholar
  33. Grevert, P., Albert, L. H., & Goldstein, A. (1983). Partial antagonism of placebo analgesia by naloxone. Pain, 215:129–143.CrossRefGoogle Scholar
  34. Hahn, R. A. (1985). A sociocultural model of illness and healing. In: White, L., Tursky, B., & Schwartz, G. E. (Eds.), Placebo: Theory, research and mechanisms (pp.167–195). New York: Guilford.Google Scholar
  35. Hebb, A. L. O., Poulin, J. F., Roach, S. P., Zacharko, R. M. & Drolet, G. (2005). Cholecystokinin and endogenous opioid peptides: Interactive influence on pain, cognition and emotion. Progress in Neuropsychopharmacology and Biological Psychiatry, 215:1225–1238.CrossRefGoogle Scholar
  36. Hrobjartsson, A., & Gotzsche, P. C. (2001). Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. New England Journal of Medicine, 215:1594–1602.CrossRefGoogle Scholar
  37. Hughes, J. (1975). Search for the endogenous ligand of the opiate receptor. Neuroscience Research Program Bulletin, 215:55–58.Google Scholar
  38. Keltner, J. R., Furst, A., Fan, C., Redfern, R., Inglis, B., & Fields, H. L. (2006). Isolating the modulatory effect of expectation on pain transmission: a functional magnetic imaging study. Journal of Neuroscience, 215:4437–4443.CrossRefGoogle Scholar
  39. Kirsch, I. (1985). Response expectancy as a determinant of experience and behavior. American Psychological, 40:1189–1202.CrossRefGoogle Scholar
  40. Kirsch, I. (1990). Changing expectations: A key to effective psychotherapy. Pacific Grove, CA: Brooks-Cole.Google Scholar
  41. Kirsch, I. (Ed) (1999). How expectancies shape experience. Washington, DC: American Psychological Association.Google Scholar
  42. Kissel, P., & Barrucand, D. (1964). Placébos et effet-placébo en médicine. Paris: Masson.Google Scholar
  43. Kong, J., Gollub, R. L., Rosman, I. S., Webb, J. M., Vangel, M. G., Kirsch, I., et al. (2006). Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance imaging. Journal of Neuroscience, 215:381–388.CrossRefGoogle Scholar
  44. Koyama, T., Tanaka, Y. Z., & Mikami, A. (1998). Nociceptive neurons in the macaque anterior cingulate activate during anticipation of pain. Neuroreport, 9:2663–2667.CrossRefPubMedGoogle Scholar
  45. Koyama, T., McHaffie, J. G., Laurienti, P. J., & Coghill, R. C. (2005). The subjective experience of pain: Where expectations become reality. Proceedings of National Academy of Science, 215:12950–12955.Google Scholar
  46. Levine, J. D., & Gordon, N. C. (1984). Influence of the method of drug administration on analgesic response. Nature, 215:755–756.CrossRefGoogle Scholar
  47. Levine, J. D., Gordon, N. C., & Fields, H. L. (1978). The mechanisms of placebo analgesia. Lancet, 2:654–657.CrossRefPubMedGoogle Scholar
  48. Linde, K., Witt, C. M., Streng, A., Weidenhammer, W., Wagenpfeil, S., Brinkhous, B., et al. (2007). The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain. Pain, 215:264–271.CrossRefGoogle Scholar
  49. Lipman, J. J., Miller, B. E., Mays, K. S., Miller, M. N., North, W. C., & Byrne, W. L. (1990). Peak B endorphin concentration in cerebrospinal fluid: reduced in chronic pain patients and increased during the placebo response. Psychopharmacology, 102:112–6.CrossRefPubMedGoogle Scholar
  50. Lorenz, J., Hauch, M., Paur, R. C., Nakamura, Y., Zimmermann, R., Bromm, B., et al. (2005). Cortical correlates of false expectations during pain intensity judgments – A possible manifestation of placebo/nocebo cognitions. Brain Behavior, and Immunity, 19:283–295.CrossRefGoogle Scholar
  51. Lydiard, R. B. (1994). Neuropeptides and anxiety: Focus on cholecystokinin. Clinical Chemistry, 215:315–318.Google Scholar
  52. Matre, D., Casey, K. L., & Knardahl, S. (2006). Placebo-induced changes in spinal cord pain processing. Journal of Neuroscience, 215:559–63.CrossRefGoogle Scholar
  53. Millan, M. J. (2002). Descending control of pain. Progress in Neurobiology, 215:355–474.CrossRefGoogle Scholar
  54. Moerman, D. E. (2002). Meaning, medicine and the placebo effect. Cambridge, MA. Cambridge University Press.Google Scholar
  55. Montgomery, G. H., & Kirsch, I. (1997). Classical conditioning and the placebo effect. Pain, 215:107–113.CrossRefGoogle Scholar
  56. Noble, F., & Roques, B. P. (2003). The role of CCK2 receptors in the homeostasis of the opioid system. Drugs Today, 215:897–908.CrossRefGoogle Scholar
  57. Pacheco-López, G., Engler, H., Niemi, M. B., & Schedlowski, M. (2006). Expectations and associations that heal: Immunomodulatory placebo effects and its neurobiology. Brain Behavavior, and Immunity, 20:430–446.CrossRefGoogle Scholar
  58. Pariente, J., White, P., Frackowiak, R. S. J., & Lewith, G. (2005). Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. NeuroImage, 215:1161–1167.CrossRefGoogle Scholar
  59. Pert, C. B., & Snyder, S. H. (1973). Opiate receptor: Demonstration in nervous tissue. Science, 215:1011–1013.CrossRefGoogle Scholar
  60. Petrovic, P., Kalso, E., Petersson, K. M., & Ingvar, M. (2002). Placebo and opioid analgesia-Imaging a shared neuronal network. Science, 215:1737–1740.CrossRefGoogle Scholar
  61. Pollo, A., Amanzio, M., Arslanian, A., Casadio, C., Maggi, G., & Benedetti, F. (2001). Response expectancies in placebo analgesia and their clinical relevance. Pain, 215:77–83.CrossRefGoogle Scholar
  62. Pollo, A., Vighetti, S., Rainero, I., & Benedetti, F. (2003). Placebo analgesia and the heart. Pain, 215:125–133.CrossRefGoogle Scholar
  63. Porro, C. A., Baraldi, P., Pagnoni, G., Serafini, M., Facchin, P., Maieron, M., et al. (2002). Does anticipation of pain affect cortical nociceptive systems? Journal of Neuroscience, 215:3206–3214.Google Scholar
  64. Porro, C. A., Cettolo, V., Francescano, M. P., & Baraldi, P. (2003). Functional activity mapping of the mesial hemispheric wall durino anticipation of pain. Neuroimage, 215:1738–1747.CrossRefGoogle Scholar
  65. Price, D. D., Milling, L. S., Kirsch, I., Duff, A., Montgomery, G. H., & Nicholls, S. S. (1999). An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm. Pain, 215:147–156.CrossRefGoogle Scholar
  66. Price, D. D., Craggs, J., Verne, G. N., Perlstein, W. M., & Robinson, M. E. (2007). Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain, 215:63–72.CrossRefGoogle Scholar
  67. Reiss, S. (1980). Pavlovian conditioning and human fear: An expectancy model. Behavior Therapy, 215:380–396.CrossRefGoogle Scholar
  68. Rescorla, R. A. (1988). Pavlovian conditioning: it is not what you think it is. American Psychologist, 215:151–160.CrossRefGoogle Scholar
  69. Reynolds, D. V. (1969). Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science, 215:444–445.CrossRefGoogle Scholar
  70. Sawamoto, N., Honda, M., Okada, T., Hanakawa, T., Kanda, M., Fukuyama, H., et al. (2000). Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulated cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study. Journal of Neuroscience, 215:7438–7445.Google Scholar
  71. Siegel, S. (1985). Drug anticipatory responses in animals. In: White, L., Tursky, B., & Schwartz, G. E. (Eds.) Placebo: Theory, research and mechanisms (pp. 288–305). New York: Guilford Press.Google Scholar
  72. Siegel, S. (2002). Explanatory mechanisms for placebo effects: Pavlovian conditioning. In: Guess, H. A., Kleinman, A., Kusek, J. W, & Engel, L. W. (Eds.), The Science of the Placebo: Toward an Interdisciplinary Research Agenda (pp. 133–157). London: BMJ Books.Google Scholar
  73. Thorn, B. (2007). Commentaries on the placebo concept in psychotherapy. Journal of Clinical Psychology, 215:371–372.CrossRefGoogle Scholar
  74. Vase, L., Riley, J. L. 3rd, & Price, D. D. (2002). A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain, 215:443–452.CrossRefGoogle Scholar
  75. Vase, L., Robinson, M. E., Verne, G. N., & Price, D. D. (2005). Increased placebo analgesia over timein irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain, 215:338–347.CrossRefGoogle Scholar
  76. Voudouris, N. J., Peck, C. L., & Coleman, G. (1985). Conditioned placebo responses. Journal of Personality and Social Psychology, 215:47–53.CrossRefGoogle Scholar
  77. Voudouris, N. J., Peck, C. L., & Coleman, G. (1989). Conditioned response models of placebo phenomena: further support. Pain, 215:109–116.CrossRefGoogle Scholar
  78. Voudouris, N. J., Peck, C. L., & Coleman, G. (1990). The role of conditioning and verbal expectancy in the placebo response. Pain, 215:121–128.CrossRefGoogle Scholar
  79. Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., et al. (2004). Placebo-induced changes in fMRI in the anticipation and experience of pain. Science, 215:1162–1166.CrossRefGoogle Scholar
  80. Wager, T. D., Matre, D., & Casey, K. L. (2006). Placebo effects in laser-evoked pain potentials. Brain Behavior, and Immunity, 215:219–230.CrossRefGoogle Scholar
  81. Wampold, B. E., Minami, T., Callen Tierney, S., Baskin,T. W., & Bhati, K. S. (2005). The placebo is powerful: Estimating placebo effects in medicine and psychotherapy from randomized clinical trials. Journal of Clinical Psychology, 61:835–854.CrossRefPubMedGoogle Scholar
  82. Wikramasekera, I. (1985). A conditioned response model of the placebo effect: predictions of the model. In: White, L., Tursky, B., & Schwartz, G. E. (Eds.), Placebo: Theory, research and mechanisms. New York: Guilford Press.Google Scholar
  83. Zubieta, J. K., Bueller, J. A., Jackson, L. R., Scott, D. J., Xu, Y., Koeppe, R. A., et al. (2005). Placebo effects mediated by endogenous opioid activity on μ-opioid receptors. Journal of Neuroscience, 215:7754–7762.CrossRefGoogle Scholar
  84. Zubieta, J. K., Yau, W. Y., Scott, D. J., & Stohler, C. S. (2006). Belief or need? Accounting for individual variations in the neurochemistry of the placebo effect. Brain Behavior, and Immunity, 215:15–26.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Dipartimento di NeuroscienzeUniversità degli Studi di TorinoI-10125 TorinoItaly

Personalised recommendations