Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.

[1]  B. Rosen,et al.  Functional connectivity of the frontoparietal network predicts cognitive modulation of pain , 2013, PAIN®.

[2]  George Lewith,et al.  Acupuncture for chronic pain: individual patient data meta-analysis. , 2012, Archives of internal medicine.

[3]  F. Miller,et al.  Lessons from recent research about the placebo effect--from art to science. , 2011, JAMA.

[4]  T. Kaptchuk Placebo studies and ritual theory: a comparative analysis of Navajo, acupuncture and biomedical healing , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[5]  K. Wiech,et al.  The Effect of Treatment Expectation on Drug Efficacy: Imaging the Analgesic Benefit of the Opioid Remifentanil , 2011, Science Translational Medicine.

[6]  K. Linde,et al.  How large are the nonspecific effects of acupuncture? A meta-analysis of randomized controlled trials , 2010, BMC medicine.

[7]  Stephanie L. Fowler,et al.  Dispositional optimism predicts placebo analgesia. , 2010, The journal of pain : official journal of the American Pain Society.

[8]  K. Linde,et al.  Are Sham Acupuncture Interventions More Effective than (Other) Placebos? A Re-Analysis of Data from the Cochrane Review on Placebo Effects , 2010, Complementary Medicine Research.

[9]  R. Gollub,et al.  The impact of placebo, psychopathology, and expectations on the response to acupuncture needling in patients with chronic low back pain. , 2010, The journal of pain : official journal of the American Pain Society.

[10]  T. Kaptchuk,et al.  Biological, clinical, and ethical advances of placebo effects , 2010, The Lancet.

[11]  Wael El-Deredy,et al.  Reproducibility of placebo analgesia: Effect of dispositional optimism , 2009, PAIN.

[12]  Ted J. Kaptchuk,et al.  An fMRI study on the interaction and dissociation between expectation of pain relief and acupuncture treatment , 2009, NeuroImage.

[13]  Ted J. Kaptchuk,et al.  Expectancy and treatment interactions: A dissociation between acupuncture analgesia and expectancy evoked placebo analgesia , 2008, NeuroImage.

[14]  B. Rosen,et al.  A Functional Magnetic Resonance Imaging Study on the Neural Mechanisms of Hyperalgesic Nocebo Effect , 2008, The Journal of Neuroscience.

[15]  Domenica Le Pera,et al.  Learning potentiates neurophysiological and behavioral placebo analgesic responses , 2008, PAIN.

[16]  L. Lasagna,et al.  Do "placebo responders" exist? , 2008, Contemporary clinical trials.

[17]  M. Hyland,et al.  Consistency of the placebo effect. , 2008, Journal of psychosomatic research.

[18]  Jian Kong,et al.  Acupuncture de qi, from qualitative history to quantitative measurement. , 2007, Journal of alternative and complementary medicine.

[19]  Pierre Rainville,et al.  Direct Comparison of Placebo Effects on Clinical and Experimental Pain , 2006, The Clinical journal of pain.

[20]  Roger B. Davis,et al.  Sham device v inert pill: randomised controlled trial of two placebo treatments , 2006, BMJ : British Medical Journal.

[21]  M. Vangel,et al.  Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging , 2006, The Journal of Neuroscience.

[22]  C. Büchel,et al.  Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network , 2006, Pain.

[23]  Andrew L. Geers,et al.  Reconsidering the role of personality in placebo effects: dispositional optimism, situational expectations, and the placebo response. , 2005, Journal of psychosomatic research.

[24]  Jian Kong,et al.  Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain. , 2005, The journal of pain : official journal of the American Pain Society.

[25]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[26]  A. Hrõbjartsson,et al.  Placebo interventions for all clinical conditions. , 2004, The Cochrane database of systematic reviews.

[27]  Val Hopwood,et al.  The placebo needle, is it a valid and convincing placebo for use in acupuncture trials? A randomised, single-blind, cross-over pilot trial , 2003, Pain.

[28]  Vilfredo De Pascalis,et al.  The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting , 2002, Pain.

[29]  T. Kaptchuk,et al.  Acupuncture: Theory, Efficacy, and Practice , 2002, Annals of Internal Medicine.

[30]  A. Hrõbjartsson,et al.  Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. , 2001, The New England journal of medicine.

[31]  T. Kaptchuk,et al.  Do medical devices have enhanced placebo effects? , 2000, Journal of clinical epidemiology.

[32]  J. Tijssen,et al.  Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos , 2000, Journal of Neurology.

[33]  E. Martin,et al.  Randomised clinical trial comparing the effects of acupuncture and a newly designed placebo needle in rotator cuff tendinitis , 1999, PAIN.

[34]  D. Price,et al.  An analysis of factors that contribute to the magnitude of placebo analgesia in an experimental paradigm , 1999, PAIN.

[35]  David Harley,et al.  The powerful placebo: from ancient priest to modern physician , 1999, BMJ.

[36]  K. Streitberger,et al.  Introducing a placebo needle into acupuncture research , 1998, The Lancet.

[37]  R. Peters The powerful placebo: from ancient priest to modern physician , 1998 .

[38]  I. Kirsch,et al.  Classical conditioning and the placebo effect , 1997, PAIN.

[39]  G. Stux Channels, Organs, and Points , 1995 .

[40]  M. Hovell,et al.  The power of nonspecific effects in healing: Implications for psychosocial and biological treatments , 1993 .

[41]  Nicholas J. Voudouris,et al.  The role of conditioning and verbal expectancy in the placebo response , 1990, Pain.

[42]  P. Wall,et al.  Textbook of pain , 1989 .

[43]  Dr. med. Gabriel Stux,et al.  Basics of Acupuncture , 1988, Springer Berlin Heidelberg.

[44]  R L Iman,et al.  Analysis of covariance using the rank transformation. , 1982, Biometrics.

[45]  W. Hall,et al.  On “Ratio scales of sensory and affective verbal pain descriptors” , 1981, Pain.

[46]  R. Dubner,et al.  Validity and sensitivity of ratio scales of sensory and affective verbal pain descriptors: Manipulation of affect by diazepam , 1978, Pain.

[47]  Ronald Dubner,et al.  Ratio scales of sensory and affective verbal pain descriptors , 1978, Pain.

[48]  P. J. Huber Robust Regression: Asymptotics, Conjectures and Monte Carlo , 1973 .

[49]  A. R. Goldman,et al.  THE DRUG‐GIVING RITUAL, VERBAL INSTRUCTIONS AND SCHIZOPHRENICS WARD ACTIVITY LEVELS , 1965, The Journal of nervous and mental disease.

[50]  S. Gelfand THE RELATIONSHIP OF EXPERIMENTAL PAIN TOLERANCE TO PAIN THRESHOLD. , 1964, Canadian journal of psychology.

[51]  Lu Cc,et al.  Chinese acupuncture and moxibustion. , 1962 .

[52]  C C LU,et al.  Chinese acupuncture and moxibustion. , 1962, Indian medical journal.

[53]  W. Holland,et al.  A double-blind study of the treatment of hypertension. , 1961, JAMA.

[54]  E. Traut,et al.  Placebos in the Treatment of Rheumatoid Arthritis and other Rheumatic Conditions * , 1957, Annals of the rheumatic diseases.

[55]  E. Traut,et al.  Study in the controlled therapy of degenerative arthritis. , 1956, A.M.A. archives of internal medicine.