Learned Nocebo Effects on Cutaneous Sensations of Pain and Itch: A Systematic Review and Meta-analysis of Experimental Behavioral Studies on Healthy Humans

Thomaidou, Mia A.; Blythe, Joseph S.; Peerdeman, Kaya J.; Laarhoven, Antoinette I. M. van; Schothorst, Myrthe M E van; Veldhuijzen, Dieuwke S.; Evers, Andrea

doi:10.1097/psy.0000000000001194

Cited by 7 publications

(3 citation statements)

References 72 publications

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“…Secondly, while interindividual variability is a highly relevant aspect to consider, it could at the same time hamper the detection of small effects. The sample size with a goal of N = 30 per experimental group was determined based on a prior power calculation and is consistent with (or even larger than) similar experimental work on visceral pain modulation [e.g., (40)] and the broader field [reviewed in (90)]. While the inclusion of diverse and complementary secondary outcome measures at different levels (behavioral, psychophysiological, brain) is consistent with sustainability goals in scientific research and will allow exploratory analyses of diverse study aims, multiple tests and comparisons will be accomplished.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study ‘NoVis’

Aulenkamp,

Icenhour,

Elsenbruch

2023

Front. Psychiatry

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The role of psychological factors in the pathophysiology and treatment of chronic visceral pain in disorders of gut-brain interactions (DGBI) is increasingly appreciated. Placebo research has underscored that expectations arising from the psychosocial treatment context and from prior experiences shape treatment responses. However, effects of negative expectations, i.e., nocebo effects, as they are likely crucial elements of DGBI patients’ clinical reality, have thus far only rarely been investigated in the context of visceral pain, with untapped potential for improved prevention and treatment. The experimental randomized-controlled pain study “NoVis,” carried out within the Collaborative Research Center (CRC) 289 (“Treatment Expectation”), aims to close gaps regarding the generation and persistence of nocebo effects in healthy volunteers. It is designed to elucidate effects of negative expectations in a multiple-threat paradigm with intensity-matched rectal distensions and cutaneous thermal stimuli, allowing to test nocebo effects in the visceral and somatic pain modalities. Negative expectations are experimentally induced by elements of doctor-patient communication (i.e., instruction) and/or by surreptitious amplification of symptom intensity (i.e., experience/learning) within a treatment context. Accordingly, the repeated measures between-subject design contains the between-group factors “treatment instruction” (negative vs. control) and “treatment experience” (negative vs. control), with volunteers randomized into four experimental groups undergoing several pain stimulation phases (repeated factor). This allows to compare the efficacy of instruction vs. experience, and more importantly, their combined effects on the magnitude of negative expectations and their impact on pain responses, which we expect will be greatest for the visceral modality. After a Baseline, short-term effects are assessed during a test phase accomplished on study day 1 (Test-1 Phase). To explore the persistence of effects, a second test phase is accomplished 1 week later (Test-2 Phase). Effects of negative expectations within and across pain modalities are assessed at the subjective and objective levels, with a focus on psychophysiological and neuroendocrine measures related to stress, fear, and anxiety. Since nocebo effects can play a considerable role in the generation, maintenance, or worsening of chronic visceral pain, and may even constitute risk factors for treatment failure, knowledge from experimental nocebo research has potential to improve treatment outcomes in DGBI and other clinical conditions associated with chronic visceral pain.

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Section: Strengths and Limitationsmentioning

confidence: 99%

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study ‘NoVis’

Aulenkamp,

Icenhour,

Elsenbruch

2023

Front. Psychiatry

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“…Experts in placebo research consented that there are several strategies to optimize placebo effects and minimize nocebo effects through communication in clinical practice [ 4 , 13 ]. For example, healthcare providers could enhance treatment effects if they outline the expected benefits from treatment [ 14 ], prevent side effects by fine-tuning the information they give to patients [ 15 – 17 ], and increase trust and satisfaction through an empathetic attitude [ 18 – 21 ]. However, experts also agree that these communication strategies are currently underutilized, and that healthcare providers should preferably be trained to address placebo and nocebo effects via their communication [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Optimizing placebo and minimizing nocebo effects through communication: e-learning and virtual reality training development

Westendorp,

van Vliet,

Meeuwis

et al. 2024

BMC Med Educ

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Background The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients’ expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands. Methods The development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases. Results Placebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0–10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0–10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future. Conclusions We have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.

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“…This phenomenon is important in clinical practice, as underlined by a large body of research demonstrating placebo and nocebo effects on painof which expectancies are the putative core mechanism (4,5). Generally, pain experiences have been found to be biased towards expectancies, known as assimilation (6,7). The influential Bayesian and predictive coding frameworks consider both the magnitude and precision of expectancies to be key determinants of their effects (1,8,9).…”

Section: Introductionmentioning

confidence: 99%

How the magnitude and precision of pain predictions shape pain experiences

Derksen¹,

Konttinen²,

Myronenko³

et al. 2023

Preprint

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In Bayesian and predictive coding frameworks, the magnitude and precision of pain expectancies are key determinants of perceptual experience However, relatively few studies have directly tested whether this holds for pain, and results so far have been inconclusive. Here, we investigated expectancy effects on pain experiences and affective responses. In two studies, healthy participants (n=30 in each study) received painful electrical stimuli preceded by explicit pain predictions. In study 1, the magnitude of pain predictions and administered pain intensities were varied. In study 2, the magnitude and precision of pain predictions were varied, while administered pain intensity was kept constant. Experienced pain intensity was the primary outcome in both studies. Study 1 found that pain experiences assimilated towards both under- and overpredictions of pain for moderate and very high pain stimuli, but this was not observed for non-painful stimuli. In addition, effects were not necessarily larger with predictions of greater magnitude. Study 2 found assimilation of pain experiences upon under- and overpredictions of pain, regardless of precision level, but no effects on EMG eyeblink startle responses. Moreover, results of both studies showed that under- and overpredictions caused disappointment and relief, respectively. In conclusion, the influence of pain predictions on pain may be more complex than assumed in current theoretical frameworks, with no systematically stronger assimilation of pain experiences to larger and more precise predictions. Since overpredictions are associated with relief, but underpredictions with disappointment, these findings underline the importance of providing realistic predictions when preparing for upcoming painful procedures.

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Learned Nocebo Effects on Cutaneous Sensations of Pain and Itch: A Systematic Review and Meta-analysis of Experimental Behavioral Studies on Healthy Humans

Cited by 7 publications

References 72 publications

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study ‘NoVis’

Nocebo effects in visceral pain: concept and design of the experimental randomized-controlled pain study ‘NoVis’

Optimizing placebo and minimizing nocebo effects through communication: e-learning and virtual reality training development

How the magnitude and precision of pain predictions shape pain experiences

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