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      The Influence of Expectation on Nondeceptive Placebo and Nocebo Effects

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          Abstract

          Nondeceptive placebo has demonstrated its efficiency in clinical practice. Although the underlying mechanisms are still unclear, nondeceptive placebo effect and nondeceptive nocebo effect may be mediated by expectation. To examine the extent to which expectation influences these effects, the present study compared nondeceptive placebo and nocebo effects with different expectation levels. Seventy-two healthy female participants underwent a standard conditioning procedure to establish placebo and nocebo effects. Sequentially, participants were randomized to one of the four experimental groups—baseline (BL), no expectation intervention (NoEI), expectation increasing (EI), and expectation decreasing (ED) groups, to receive either no intervention or interventions through different verbal suggestions that modulated their expectation. Placebo and nocebo effects were established in all four groups after the conditioning phase. However, after disclosing the placebo and nocebo, the analgesic and the hyperalgesic effects only persisted in the EI group, when compared with the BL group. Our results provide evidence highlighting the critical role of increased expectation in nondeceptive placebo and nocebo effects. The finding suggests that open-label placebo or nocebo per se might be insufficient to induce strong analgesic or hyperalgesic response and sheds insights into administrating open-label placebo and avoiding open-label nocebo in clinical practice.

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          Most cited references35

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          Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome

          Background Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent. Trial Registration ClinicalTrials.gov NCT01010191
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            Habituation: A model phenomenon for the study of neuronal substrates of behavior.

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              Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses.

              The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT(1B/1D) agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.
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                Author and article information

                Contributors
                Journal
                Pain Res Manag
                Pain Res Manag
                PRM
                Pain Research & Management
                Hindawi
                1203-6765
                1918-1523
                2018
                19 March 2018
                : 2018
                : 8459429
                Affiliations
                1CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China
                2Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
                3Faculty of Psychology, Southwest University, Chongqing, China
                4Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, Hunan, China
                Author notes

                Academic Editor: Filippo Brighina

                Author information
                http://orcid.org/0000-0003-0645-4428
                http://orcid.org/0000-0001-7628-1820
                http://orcid.org/0000-0001-7698-8842
                http://orcid.org/0000-0002-6264-9812
                http://orcid.org/0000-0001-7586-5576
                http://orcid.org/0000-0001-7003-2903
                Article
                10.1155/2018/8459429
                5884148
                29755621
                bc4478fe-848e-49b5-97c2-e800a6c9b125
                Copyright © 2018 Hua Wei et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2017
                : 30 January 2018
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31471082
                Award ID: 31671141
                Award ID: 31701000
                Award ID: 31771240
                Funded by: Chongqing Research Program of Basic Research and Frontier Technology
                Award ID: cstc2015jcyjBX0050
                Funded by: Chinese Academy of Sciences
                Award ID: Y6CX021008
                Award ID: Y6CX281007
                Funded by: Hunan Normal University
                Award ID: CBL201605
                Categories
                Clinical Study

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