title: How the number of learning trials affects placebo and nocebo responses.
abstract: Conditioning procedures are used in many placebo studies because evidence suggests that conditioning-related placebo responses are usually more robust than those induced by verbal suggestions alone. However, it has not been shown whether there is a causal relation between the number of conditioning trials and the resistance to extinction of placebo and nocebo responses. Here we test the effects of either one or four sessions of conditioning on the modulation of both non-painful and painful stimuli delivered to the dorsum of the foot. Placebo and nocebo manipulations were obtained by pairing green or red light to a series of stimuli that were made lower or higher with respect to a yellow light associated with a series of control stimuli. Subjects were told that the lights would indicate a treatment that would reduce or increase non-painful and painful stimuli to the foot. They were randomly assigned to either Group 1 or 2. Group 1 underwent one session of conditioning and Group 2 received four sessions of conditioning. We found that one session of conditioning (Group 1) induced nocebo responses, but not placebo responses in no pain condition. After one session of conditioning, we observed both nocebo and placebo responses to painful stimulation. However, these effects extinguished over time. Conversely, four sessions of conditioning (Group 2) induced robust placebo and nocebo responses to both non-painful and painful stimuli that persisted over the entire experiment. These findings suggest that the strength of learning may be clinically important for producing long-lasting placebo effects.
authors.affiliation: Department of Neuroscience, University of Turin Medical School and National Institute of Neuroscience, Turin, Italy MR-Research Center and Osher Center, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden National Center for Complementary and Alternative Medicine (NCCAM) & Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, USA Department of Psychology and Neuroscience, University of Colorado, Boulder, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Colloca
authors.forename: Predrag
authors.initials: P
authors.lastname: Petrovic
authors.forename: Tor D
authors.initials: TD
authors.lastname: Wager
authors.forename: Martin
authors.initials: M
authors.lastname: Ingvar
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003213:Conditioning, Psychological / Q000502:physiology*; D004558:Electric Stimulation / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use*; D011581:Psychological Tests; D011601:Psychophysics / Q000379:methods; D013223:Statistics as Topic; D013997:Time Factors; D055815:Young Adult
chemical_list: D010919:Placebos
references.citation: J Psychosom Res. 2005 Feb;58(2):121-7
references.pmid: 15820839
references.citation: Am J Med. 1954 Jun;16(6):770-9
references.pmid: 13158365
references.citation: Science. 1955 Jul 22;122(3160):157-8
references.pmid: 14396377
references.citation: Pain. 2009 Nov;146(1-2):194-8
references.pmid: 19692178
references.citation: Cognition. 2009 Dec;113(3):350-364
references.pmid: 18722597
references.citation: Pain. 2008 May;136(1-2):211-8
references.pmid: 18372113
references.citation: Neuron. 2005 Jun 16;46(6):957-69
references.pmid: 15953423
references.citation: Pain. 2009 Jul;144(1-2):28-34
references.pmid: 19278785
references.citation: Pain. 2006 Sep;124(1-2):126-33
references.pmid: 16701952
references.citation: J Physiol. 1967 Jun;190(3):541-62
references.pmid: 6051786
references.citation: Annu Rev Psychol. 2008;59:565-90
references.pmid: 17550344
references.citation: Arch Gen Psychiatry. 1961 Jun;4:561-71
references.pmid: 13688369
references.citation: Headache. 1973 Apr;13(1):1-11
references.pmid: 4572208
references.citation: Science. 2009 Feb 27;323(5918):1226-9
references.pmid: 19197022
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:33-60
references.pmid: 17666008
references.citation: Pain. 1997 Aug;72(1-2):107-13
references.pmid: 9272794
references.citation: Eur J Neurosci. 2008 Jul;28(2):379-88
references.pmid: 18702709
references.citation: Pain. 2009 Sep;145(1-2):2-3
references.pmid: 19559528
references.citation: Pain. 2007 Mar;128(1-2):31-9
references.pmid: 17030095
references.citation: Brain Behav Immun. 2010 Feb;24(2):176-85
references.pmid: 19698779
references.citation: Pain. 1989 Jul;38(1):109-116
references.pmid: 2780058
references.citation: Science. 2004 Feb 20;303(5661):1162-7
references.pmid: 14976306
references.citation: Neuron. 2008 Jul 31;59(2):195-206
references.pmid: 18667148
references.citation: Pain. 2009 Sep;145(1-2):24-30
references.pmid: 19523766
references.citation: Psychol Rep. 1965 Oct;17(2):555-62
references.pmid: 5833741
references.citation: J Pers Soc Psychol. 1985 Jan;48(1):47-53
references.pmid: 3981392
references.citation: Annu Rev Psychol. 2010;61:273-301
references.pmid: 19575617
references.citation: Pain. 1990 Oct;43(1):121-128
references.pmid: 2277714
references.citation: Psychol Bull. 2004 Mar;130(2):341-3; discussion 344-5
references.pmid: 14979776
references.citation: Clin Pharmacol Ther. 1966 Jul-Aug;7(4):447-54
references.pmid: 5939967
references.citation: Science. 2001 Aug 10;293(5532):1164-6
references.pmid: 11498597
references.citation: Pain. 2008 Oct 15;139(2):306-314
references.pmid: 18538928
references.citation: Am Psychol. 1988 Mar;43(3):151-60
references.pmid: 3364852
references.citation: Physiol Behav. 2005 Apr 13;84(5):807-14
references.pmid: 15885259
references.citation: J Clin Psychol. 2004 Apr;60(4):369-92
references.pmid: 15022268
references.citation: Curr Ther Res Clin Exp. 1968 Mar;10(3):136-43
references.pmid: 4967001
references.citation: Nat Neurosci. 2004 Jun;7(6):587-8
references.pmid: 15146189
references.citation: J Neurosci. 1999 Jan 1;19(1):484-94
references.pmid: 9870976
references.citation: FASEB J. 2002 Dec;16(14):1869-73
references.pmid: 12468450
references.citation: J Neurosci. 2003 May 15;23(10):4315-23
references.pmid: 12764120
references.citation: Pain. 1999 Nov;83(2):147-56
references.pmid: 10534585