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Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in understanding the mechanisms underlying placebo response. In the present study, we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain. First, we found that part of...
Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this assumption, we tested the placebo response in a population...
This systematic review assesses six experimental studies into the mechanism of placebo analgesia in human subjects suffering from clinical pain or experimentally induced ischaemic arm pain. Due to their sophisticated designs, these studies probably provide the best evidence that placebo analgesia exists. They also indicate that placebo analgesia is mediated by endogenous opiates. However, there...
Placebo analgesia was produced by conditioning trials wherein heat induced experimental pain was surreptitiously reduced in order to test psychological factors of expectancy and desire for pain reduction as possible mediators of placebo analgesia. The magnitudes of placebo effects were assessed after these conditioning trials and during trials wherein stimulus intensities were reestablished to original...
This study reports how placebo analgesia was produced by conditioning whereby the intensity of electric stimulation was surreptitiously reduced in order to examine the contribution of psychological factors of suggestibility and expectancy on placebo analgesia. This strategy was used in order to manipulate expectancy for pain reduction. The magnitudes of the placebo effects were estimated after a manipulation...
A previous meta-analysis of clinical analgesic trial studies showed generally low magnitudes of placebo analgesia (N. Engl. J. Med. 344 (2001) 1594). However, as studies included in their analysis used only placebo as a control condition, we conducted two meta-analyses, one in which 23 studies used only placebo as a control condition, and one in which 14 studies investigated placebo analgesic mechanisms...
In order to investigate external factors that may influence the magnitude of placebo analgesia as well as psychological factors that mediate placebo analgesia, 13 irritable bowl syndrome (IBS) patients rated evoked rectal distension and cutaneous heat pain under the conditions of natural history (NH), rectal placebo (RP), rectal nocebo (RN), rectal lidocaine (RL) and oral lidocaine (OL). Patients...
Some studies indicate that placebo analgesia is stronger when pre-conditioning with effective analgesic treatments is performed, thereby suggesting that the placebo response is a learning phenomenon. Here we further tested this hypothesis in order to better understand when and how previous experience affects the placebo analgesic response. To do this, we used a conditioning procedure whereby the intensity...
Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. This functional magnetic resonance imaging (fMRI) study examined whether placebo analgesia...
The effectiveness of placebos is unchallenged. However, it is still not clear on which mechanisms the placebo effect is based. Besides expectancy theories, classical conditioning is discussed as a major explanatory model. In an experimental conditioning design we tested 96 participants, 48 with atopic dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female). All of them received...
Expectation and conditioning are supposed to be the two main psychological mechanisms for inducing a placebo response. Here, we further investigate the effects of both expectation, which was induced by verbal suggestion alone, and conditioning at the level of N1 and N2–P2 components of CO 2 laser-evoked potentials (LEPs) and subjective pain reports. Forty-four healthy volunteers were pseudorandomly...
Previously, we demonstrated that placebo analgesia (PA) accompanies reductions in neural activity during painful stimulation. This study investigated areas of the brain where the neural activity was increased during PA. The literature has associated PA with two potential mechanisms of action; one sustained (e.g., engaged for the duration of PA), the other, transitory (e.g., a feedback mechanism)....
The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before,...
Recent meta-analyses find various magnitudes of placebo analgesia effects in placebo mechanism trials versus placebo control trials, which have led to debate. To further investigate the magnitude of placebo analgesia in placebo mechanism trials the databases “PubMed”, “PsycINFO” and “Web of Science” (2002–2007) were searched with the term “placebo analgesia”. Twenty-one articles including 24 studies...
Expectations and beliefs modulate the experience of pain, which is particularly evident in placebo analgesia. The dorsolateral prefrontal cortex (DLPFC) has been associated with pain regulation and with the generation, maintenance and manipulation of cognitive representations, consistent with its role in expectation. In a heat-pain paradigm, we employed non-invasive low-frequency repetitive transcranial...
Placebo analgesia is the occurrence of an analgesic drug effect without drugs. The response is learned through conditioning and mediated by expectancy. It lies on the up-regulation of the pain-modulating areas and the down-regulation of the pain-encoding regions. A further mechanism is the retrieval of the brain circuit activity previously excited by drugs. We describe the case of an infant affected...
Fear of pain (FOP) and its effect on placebo analgesia was investigated. It was hypothesized that FOP should interfere with placebo-mediated pain inhibition and result in weaker placebo responding in pain intensity, pain unpleasantness, stress, and event-related potentials to contact heat pain. Thirty-three subjects participated in a balanced 2 condition (natural history, placebo)×3 test (pretest,...
Investigating dose-dependent effects of placebo analgesia (PA) in laboratory subjects undergoing pain testing, we evaluated 2 hypotheses: (1) greater expectancy for relief produces greater PA, and (2) cued expectancy for relief triggered by a predictive cue leads to more enhanced analgesia than does passive expectancy (no predictive cue). We used conditioning procedures in which 84 subjects experienced...
This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level–dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing...
Fear was induced by the anticipation of electric shock in order to investigate whether fear reduced the effectiveness of a placebo intervention on reported pain and the acoustic startle reflex. Thirty-three subjects participated in a 3 Condition (Natural History [NH], Placebo [P], Placebo+Fear [PF])×3 Test (Pretest, Posttest 1, Posttest 2) within-subject design, tested on 3 separate days. Measures...
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