Abstract
The magnitude of placebo analgesia effect appears to be large in chronic pain patients experiencing hyperalgesic states. So far, placebo effects have primarily been investigated in idiopathic pain conditions, such as irritable bowel pain syndrome, but more recently they have also been investigated in neuropathic pain patients, in which the underlying nerve injury is known. Expected pain levels and emotional feelings are central to placebo effects in both types of pain. They appear to help patients to engage in a mindset for pain relief and activate the pain-modulating system. Furthermore, expectations, emotional feelings, and the experience of pain seem to interact over time, thereby maintaining or enhancing the pain-relieving effect. Expectations and emotional feelings also contribute to the effect of active drugs, and recent studies indicate that drug effects and placebo effects interact in ways that may complicate the interpretations of the findings from clinical trials. It is suggested that expectations and emotional feelings may act as additional or alternative measures in the testing of new pharmacological agents, thereby improving the understanding of the interaction between pharmacological effects and placebo effects, which may have far-reaching implications for research and clinical practice.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Amanzio M, Pollo A, Maggi G, Benedetti F (2001) Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 90:205–215
Amanzio M, Corrazini LL, Vase L, Benedetti F (2009) A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain 146:261–269
Andersen LO (1997) Placebo – historisk og kulturelt. In: Andersen OK, Claësson MH, Hjóbjartsson A, Sørensen AN (eds) Placebo. Historie, biologi, og effekt. Akademisk Forlag A/S, Copenhagen, pp 69–120
Benedetti F (2009) Placebo effects. Understanding the mechanisms in health and disease. Oxford University Press, Oxford
Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M et al (2011) The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med 3:70ra14
Conboy LA, Wasserman RH, Jacobson EE, Davis RB, Legedza AT, Park M et al (2006) Investigating placebo effects in irritable bowel syndrome: a novel research design. Contemp Clin Trials 27:123–134
Craggs JG, Price DD, Verne GN, Perlstein WM, Robinson MM (2007) Functional brain interactions that serve cognitive-affective processing during pain and placebo analgesia. NeuroImage 38:720–729
Craggs JG, Price DD, Perlstein WM, Verne GN, Robinson ME (2008) The dynamic mechanisms of placebo induced analgesia: evidence of sustained and transient regional involvement. Pain 139:660–669
Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I et al (2012) Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain 153:1148–1158
Finnerup NB, Sindrup SH, Jensen TS (2010) The evidence for pharmacological treatment of neuropathic pain. Pain 150:573–581
Flaten MA, Aslaksen PM, Lyby PS, Bjørkedal E (2011) The relation of emotions to placebo analgesia. Philos Trans R Soc Lond B Biol Sci 366:1818–1827
Hammami MM, Al-Gaai EA, Alvi S, Hammami MB (2010) Interaction between drug and placebo effects: a cross-over balanced placebo design trial. Trials 11:1–10
Harrington A (1997) The placebo effect. An interdisciplinary exploration. Harvard University Press, Cambridge
Hróbjartsson A, Gøtzsche PC (2001) Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 344:1594–1602
Hróbjartsson A, Gøtzsche PC (2004) Is the placebo powerless? Update of a systematic review with 52 new randomised trials comparing placebo with no treatment. J Intern Med 256:91–100
Hróbjartsson A, Gøtzsche PC (2010) Placebo interventions for all clinical conditions. Cochrane Database Syst Rev 1, CD003974
Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice AS et al (2011) A new definition of neuropathic pain. Pain 152:2204–2205
Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP et al (2010) Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS ONE 5:e15591
Katz J, Finnerup NB, Dworkin RH (2008) Clinical trial outcome in neuropathic pain: relationship to study characteristics. Neurology 70:263–272
Khan A, Detke M, Khan SR, Mallinckrodt C (2003) Placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 191:211–218
Lieberman MD, Jarcho JM, Berman S, Naliboff BD, Suyenobu BY, Mandelkern M et al (2004) The neural correlates of placebo effects: a disruption account. NeuroImage 22:447–455
Lund K, Vase L, Petersen GL, Jensen TS, Finnerup NB (2014) Randomised controlled trials may underestimate drug effects: balanced placebo trial design. PLoS ONE 9(1):e84104. doi:10.1371/journal.pone.0084104. eCollection 2014
Moerman DE (2000) Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure. Med Anthropol Q 14:51–72
Montgomery G, Kirsch I (1997) Classical conditioning and the placebo effect. Pain 72:107–113
Petersen GL, Finnerup NB, Nørskov KN, Grosen K, Pilegaard HK, Benedetti F et al (2012) Placebo manipulations reduce hyperalgesia in neuropathic pain. Pain 153:1292–1300
Piche M, Bouin M, Arsenault M, Poitras P, Rainville P (2011) Decreased pain inhibition in irritable bowel syndrome depends on altered descending modulation and higher-order brain processes. Neuroscience 195C:166–175
Price DD (1999) Psychological mechanisms of pain and analgesia. IASP Press, Seattle
Price DD, Barrell JJ (2012) Inner experience and neuroscience: merging both perspectives. MIT Press, Cambridge
Price DD, Vase L (2013) The contributions of desire, expectation and reduced negative emotions to placebo anti-hyperalgesia in irritable bowel syndrome. In: Colloca L, Flaten M, Meissner K (eds) Placebo and pain. From bench to bedside. Elsevier, Amsterdam, pp 215–226
Price DD, Milling LS, Kirsch I, Duff A, Montgomery GH, Nicholls SS (1999) An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm. Pain 83:147–156
Price DD, Riley JL III, Vase L (2003) Reliable differences in placebo effects between clinical analgesic trials and studies of placebo analgesia mechanisms. Pain 104:715–716
Price DD, Craggs J, Verne GN, Perlstein WM, Robinson ME (2007) Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 127:63–72
Price DD, Finniss DG, Benedetti F (2008) A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol 59:565–590
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 55:325–336
Silberman S (2009) Placebos are getting more effective. Drugmakers are desperate to know why. Wired Magazine. http://www.wired.com. Accessed 24 Aug 2009
Usdin S (2011) Product discovery and development: shaking the cup for pain. BioCentury 19:13–14
Vase L, Petersen GL (2013) Conceptualizations and magnitudes of placebo analgesia effects across meta-analyses and experimental studies. In: Colloca L, Flaten M, Meissner K (eds) Placebo and pain. From bench to bedside. Elsevier, Amsterdam, pp 203–213
Vase L, Riley JL III, Price DD (2002) A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain 99:443–452
Vase L, Robinson ME, Verne GN, Price DD (2003) The contribution of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients. An empirical investigation. Pain 105:17–25
Vase L, Price DD, Verne GN, Robinson ME (2004) The contribution on changes in expected pain levels and desire for pain relief to placebo analgesia. In: Price DD, Bushnell MC (eds) Psychological methods of pain control: basic science and clinical perspectives. IASP Press, Seattle, pp 207–234
Vase L, Robinson ME, Verne GN, Price DD (2005) Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain 115:338–347
Vase L, Petersen GL, Riley JL 3rd, Price DD (2009) Factors contributing to large analgesic effects in placebo mechanism studies conducted between 2002 and 2007. Pain 145:36–44
Vase L, Nørskov KN, Petersen GL, Price DD (2011) Patients’ direct experiences as central elements of placebo analgesia. Philos Trans R Soc Lond B Biol Sci 366:1913–1921
Verne GN, Robinson ME, Vase L, Price DD (2003) Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Pain 105:223–230
Verne GN, Price DD, Callam CS, Zhang B, Peck J, Zhou Q (2012) Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N-Methyl-D-aspartate receptors. J Pain 13:901–909
Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ et al (2004) Placebo-induced changes in fMRI in the anticipation and experience of pain. Science 303:1162–1167
Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54:1063–1070
Acknowledgment
“The research leading to these results is part of the Europain Collaboration, which has received support from the Innovative Medicines Initiative Joint Undertaking, under Grant Agreement No. 115007, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution” www.imi.europa.eu. The funding source had the possibility to comment on the design and reporting of the study, but had no role in the collection, analysis and interpretation of data and decision to submit for publication. Ethical approval: This study was approved by the ethical committee of the Central Denmark Region
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Vase, L., Petersen, G.L., Lund, K. (2014). Placebo Effects in Idiopathic and Neuropathic Pain Conditions. 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_7
Download citation
DOI: https://doi.org/10.1007/978-3-662-44519-8_7
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-44518-1
Online ISBN: 978-3-662-44519-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)