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      Highlights from the 2013 Science of Placebo thematic workshop

      meeting-report

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          Abstract

          In the last 30 years, a converging series of laboratory experiments, clinical trials, and neurocognitive studies have identified several key mechanisms of placebo effects. These studies suggest not only that placebo responses may be ubiquitous across research and clinical settings, but also that they can significantly modulate symptoms across a wide spectrum of highly prevalent conditions such as acute pain, chronic pain, anxiety, depression, Parkinson’s disease, and nausea, just to name a few. In order to inform the medical community about the most recent advances in the field of placebo studies, a thematic workshop entitled “The Science of Placebo” was held at the Beth Israel Deaconesses Medical Center (BIDMC), Harvard Medical School, in Boston (MA), on the 19–20 of June 2013. The workshop, sponsored by The Robert Wood Johnson Foundation, was organised by the Program in Placebo Studies and the Therapeutic Encounter, a Harvard-wide network of researchers dedicated to the study of the placebo phenomenon hosted by the BIDMC. The event was structured as a series of four public lectures, each delivered by a leading investigator in the field of placebo studies. The four keynote speakers were Fabrizio Benedetti, professor of neurophysiology and human physiology at the University of Turin Medical School and at the National Institute of Neuroscience in Italy; Tor Wager, director of the Cognitive and Affective Control Laboratory and associate professor of psychology and neuroscience at the University of Colorado; Predrag Petrovic, psychiatrist and researcher in the Department of Clinical Neuroscience at the Karolinska Institute in Stockholm; and Ted Kaptchuk, director of the Program in Placebo Studies and associate professor of medicine at Harvard Medical School.

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          Most cited references11

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          Ventromedial prefrontal-subcortical systems and the generation of affective meaning.

          The ventromedial prefrontal cortex (vmPFC) comprises a set of interconnected regions that integrate information from affective sensory and social cues, long-term memory, and representations of the 'self'. Alhough the vmPFC is implicated in a variety of seemingly disparate processes, these processes are organized around a common theme. The vmPFC is not necessary for affective responses per se, but is critical when affective responses are shaped by conceptual information about specific outcomes. The vmPFC thus functions as a hub that links concepts with brainstem systems capable of coordinating organism-wide emotional behavior, a process we describe in terms of the generation of affective meaning, and which could explain the common role played by the vmPFC in a range of experimental paradigms. Copyright © 2012 Elsevier Ltd. All rights reserved.
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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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              Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.

              Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.
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                Author and article information

                Journal
                Ecancermedicalscience
                Ecancermedicalscience
                ecancermedicalscience
                ecancermedicalscience
                Cancer Intelligence
                1754-6605
                2013
                04 September 2013
                : 7
                : 346
                Affiliations
                University of Milan, Department of Health Sciences, Milan 20142, Italy
                European School of Molecular Medicine, Milan 20139, Italy
                European Institute of Oncology, Milan 20141, Italy
                FOLSATEC, Milan 20139, Italy
                Author notes
                Correspondence to: Marco Annoni. marco.annoni@ 123456ieo.eu
                Article
                can-7-346
                10.3332/ecancer.2013.346
                3760811
                24019848
                ae76337e-5690-4ca2-bba4-1e4c6f4ce10f
                © the authors; licensee ecancermedicalscience.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 July 2013
                Categories
                Conference Report

                Oncology & Radiotherapy
                placebo,placebo effect,placebo response,pain,chronic pain,depression,parkinson,fmri,pet,randomisation,clinical trial,acupuncture

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