Understanding placebo and nocebo responses for pain management.
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ABSTRACT:
SUBMITTER: Colloca L
PROVIDER: S-EPMC4142751 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Publications
Understanding placebo and nocebo responses for pain management.
Colloca Luana L Grillon Christian C
Current pain and headache reports 20140601 6
Placebo analgesia makes individuals experience relief of their pain simply by virtue of the anticipation of a benefit. A reduction of pain can occur also when placebos follow the administration of active and effective painkillers. In fact, studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids in both humans and animals. Finally, social support and observational learning also lead to analgesic effects. Thus, different psychological fact ...[more]
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Project description:Introduction:Research on learning in placebo and nocebo has relied predominantly on Pavlovian conditioning procedures. Operant learning procedures may more accurately model learning in real-life situations in which placebo and nocebo effects occur. Objectives:To investigate the development and persistence of placebo and nocebo effects using an operant avoidance learning task. Methods:Pain-free participants (n = 58) could learn to avoid pain by performing movements that differed in difficulty and intensity of painful stimulation. Participants performed movements in 2 contexts. In the high cost of avoidance context, pain stimulus intensity reduced with increasing movement difficulty. In the low cost of avoidance context, contingencies were reversed. Participants rated pain expectations and pain intensity. During test, movement difficulties were unchanged, but participants always received a medium-intensity pain stimulus. Placebo and nocebo effects were defined as lower/higher pain intensity ratings for trajectories that previously resulted in low/high-intensity compared with medium-intensity stimulation. Results:As expected, participants acquired differential movement-pain expectations and differential movement choices. Testing with a medium-intensity pain stimulus quickly erased differences in movement choice across contexts, but differences in pain expectations were maintained. Pain modulation across context was in line with movement-pain expectations. However, we only observed placebo effects within the low cost of avoidance context and found no evidence of nocebo effects. Conclusion:Operant learning can change pain expectations, pain modulation, and pain-related avoidance behavior. Persisting pain expectations suggest that acquired pain beliefs may be resistant to disconfirmation, despite self-initiated experience with novel pain-movement contingencies.
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Project description:BackgroundResearch has demonstrated that personality characteristics, such as optimism are associated with placebo/nocebo responding. The present study investigated whether written information about the optimism of a placebo/nocebo provider can influence the occurrence of reported placebo/nocebo side effects.MethodWe analyzed data from 201 females (mean age = 26 years) who participated in a "clinical study on a new massage oil with stone clover extract." The oil (sunflower oil) was introduced as either eliciting a negative side effect (unpleasant itching; "nocebo oil") or a positive side effect (pleasant tingling; "placebo oil"). The administration of the oil was combined with written information about the maker of the product. The oil maker was either portrayed as a very optimistic person or no personal information was provided (only the company name). The participants had no personal contact with the experimenter and received all materials and instructions per post.ResultsThe participants reported more frequent and intense itching when they received a nocebo suggestion compared to a placebo suggestion. Positive tingling sensations were reported more frequently than itching but did not differ between the placebo/nocebo conditions. Information about the optimism of the oil maker was associated with a lower frequency of reported side effects (adverse and beneficial).ConclusionThis study demonstrated that it is sufficient to provide participants with written information about an inert substance to elicit the suggested side effect. Information about the provider's optimistic personality did not specifically influence reported side effects. Future studies should focus on how to adapt written information about a drug/product to minimize adverse side effects and to maximize positive side effects.
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Project description:This study aimed to identify electrophysiological correlates of nocebo-augmented pain. Nocebo hyperalgesia (i.e., increases in perceived pain resulting from negative expectations) has been found to impact how healthy and patient populations experience pain and is a phenomenon that could be better understood in terms of its neurophysiological underpinnings. In this study, nocebo hyperalgesia was induced in 36 healthy participants through classical conditioning and negative suggestions. Electroencephalography was recorded during rest (pre- and post-acquisition) and during pain stimulation (baseline, acquisition, evocation) First, participants received baseline high thermal pain stimulations. During nocebo acquisition, participants learned to associate an inert gel applied to their forearm with administered high pain stimuli, relative to moderate intensity control stimuli administered without gel. During evocation, all stimuli were accompanied by moderate pain, to measure nocebo responses to the inert gel. Pre- to post-acquisition beta-band alterations in long-range temporal correlations (LRTC) were negatively associated with nocebo magnitudes. Individuals with strong resting LRTC showed larger nocebo responses than those with weaker LRTC. Nocebo acquisition trials showed reduced alpha power. Alpha power was higher while LRTC were lower during nocebo-augmented pain, compared to baseline. These findings support nocebo learning theories and highlight a role of nocebo-induced cognitive processing.
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Project description:Classical theories suggest placebo analgesia and nocebo hyperalgesia are based on expectation and conditioned experience. Whereas the neural mechanism of how expectation modulates placebo and nocebo effects during pain anticipation have been extensively studied, little is known about how experience may change brain networks to produce placebo and nocebo responses. We investigated the neural pathways of direct and observational conditioning for conscious and nonconscious conditioned placebo/nocebo effects using magnetoencephalography and a face visual cue conditioning model. We found that both direct and observational conditioning produced conscious conditioned placebo and nocebo effects and a nonconscious conditioned nocebo effect. Alpha band brain connectivity changes before and after conditioning could predict the magnitude of conditioned placebo and nocebo effects. Particularly, the connectivity between the rostral anterior cingulate cortex and middle temporal gyrus was an important indicator for the manipulation of placebo and nocebo effects. Our study suggests that conditioning can mediate our pain experience by encoding experience and modulating brain networks.
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Project description:Health care providers use treatments whose effectiveness derives partially or completely from 'nonspecific' factors, frequently referred to as placebo effects. Although the ethics of interventional placebo use continues to be debated, evidence suggests that placebos can produce clinically meaningful analgesic effects. Burgeoning evidence suggest that patients with chronic pain might be open to placebo treatments in certain contexts despite limited knowledge of their well-established psychoneurobiological underpinnings. In this investigation we sought to examine the effects of a brief, mechanism-based placebo analgesia educational intervention on aspects placebo knowledge and acceptability. Participants with chronic musculoskeletal pain completed a web-based survey in which they rated their knowledge of placebo analgesia, assessed placebo acceptability across different medical contexts, and evaluated 6 unique patient-provider treatment scenarios to assess the role of treatment effectiveness and deception on patient-provider attributions. Using a pre-post design, participants were randomized to receive either a placebo educational intervention or an active control education. Results showed that the educational intervention greatly improved perceptions of placebo knowledge, effectiveness, and acceptability, even in deceptive treatment contexts. This was the first study of its kind to show the value of an educational intervention in increasing openness to and knowledge of placebo analgesic interventions among patients with chronic musculoskeletal pain.In this we article highlight how patients with chronic pain might be open to placebo interventions, particularly adjunct and/or complementary treatments, when provided education on the neurobiological and psychological mechanisms that underlie placebo effects. Study findings highlight ethically acceptable ways to potentially use placebo factors to enhance existing pain treatments and improve patient health outcomes.
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Project description:Harnessing placebo and nocebo effects has significant implications for research and medical practice. Placebo analgesia and nocebo hyperalgesia, the most well-studied placebo and nocebo effects, are thought to initiate from the dorsal lateral prefrontal cortex (DLPFC) and then trigger the brain's descending pain modulatory system and other pain regulation pathways. Combining repeated transcranial direct current stimulation (tDCS), an expectancy manipulation model, and functional MRI, we investigated the modulatory effects of anodal and cathodal tDCS at the right DLPFC on placebo analgesia and nocebo hyperalgesia using a randomized, double-blind and sham-controlled design. We found that compared with sham tDCS, active tDCS could 1) boost placebo and blunt nocebo effects and 2) modulate brain activity and connectivity associated with placebo analgesia and nocebo hyperalgesia. These results provide a basis for mechanistic manipulation of placebo and nocebo effects and may lead to improved clinical outcomes in medical practice.
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Project description:BACKGROUND:Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. METHODS:A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. RESULTS:There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. CONCLUSIONS:The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.
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Project description:The aim of this study was to examine the relationships among classical conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia. A total of 42 healthy volunteers were randomly assigned to three groups: placebo, nocebo, and control. They received 96 electrical stimuli, preceded by either orange or blue lights. A hidden conditioning procedure, in which participants were not informed about the meaning of coloured lights, was performed in the placebo and nocebo groups. Light of one colour was paired with pain stimuli of moderate intensity (control stimuli), and light of the other colour was paired with either nonpainful stimuli (in the placebo group) or painful stimuli of high intensity (in the nocebo group). In the control group, both colour lights were followed by control stimuli of moderate intensity without any conditioning procedure. Participants rated pain intensity, expectancy of pain intensity, and fear. In the testing phase, when both of the coloured lights were followed by identical moderate pain stimuli, we found a significant analgesic effect in the placebo group, and a significant hyperalgesic effect in the nocebo group. Neither expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia. It appears that a hidden conditioning procedure, without any explicit verbal suggestions, elicits placebo and nocebo effects, however we found no evidence that these effects are predicted by either expectancy or fear. These results suggest that classical conditioning may be a distinct mechanism for placebo and nocebo effects.
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Project description:INTRODUCTION:Placebo and nocebo effects form part of all therapeutic environments and play a significant role in the effectiveness of treatment outcomes. Patient expectancies drive these phenomena, which can be shaped through contextual factors including verbal suggestions, conditioning, and social observation. OBJECTIVES:This review seeks to identify the biopsychosocial factors of the patient-practitioner interaction that play a role in the development of placebo and nocebo effects, as well as the anthropological elements of the biodynamic process of relating that are meaningful in the development of expectancies. METHODS:We conducted a narrative review of frameworks of the placebo and nocebo effect, including the impact of expectancies and interpersonal relationships in the context of healing and the clinical setting. RESULTS:Expectancies leading to placebo and nocebo effects can be modified by macro and micro factors, such as culture and society, as well as individual psychobiological traits, respectively. The developmental sociobiological adaptations that form and consolidate mindsets and meaningful contexts play an important role in shaping patient expectancies, as well as patients' conscious and subconscious reactions to signs and actions taking place within the clinical environment. Practitioner characteristics, like empathy, friendliness, and competence, favor the formation of positive expectancies. Caring and warm patient-practitioner interactions can enhance the therapeutic value of clinical encounters when patients' positive expectancies are actively encouraged and engaged. CONCLUSION:A patient-centered approach rooted in demonstrating care and empathy can positively enhance a patient's experience within the clinical environment and activate psychosociobiological adaptations associated with the placebo phenomenon. Pain patients could particularly benefit from non-invasive approaches for improving treatment effectiveness and quality-of-life.
| S-EPMC6176716 | biostudies-literature