Pre-Exposure, But Not Overshadowing, Inhibits Nocebo Hyperalgesia

Colagiuri, Ben; Park, J.; Barnes, Kirsten; Sharpe, Louise; Boakes, Robert A.; Colloca, Luana; Livesey, Evan J.

doi:10.1016/j.jpain.2021.02.008

Cited by 11 publications

(4 citation statements)

References 49 publications

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“…The current results suggest that decreasing vaccine hesitancy levels is warranted in vaccinated persons as well, as it should lead to lower side-effect levels. Second, our results revealing a nocebo component of these side-effects suggest that these side-effects may be directly ameliorated by a variety of specific interventions that have been documented to reduce nocebo effects 18 ; e.g., interventions that decrease one’s anxiety 19 , interventions that include different forms of conditioning to induce more positive expectations 34 or methods that challenge negative expectations, such as pre-exposure 35 . In addition, the same information, which is typically framed negatively, can be communicated positively; such positive framing also reduces nocebo effects 36 , 37 .…”

Section: Discussionmentioning

confidence: 84%

Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination

Levin

Palgi

Ben–Ezra

et al. 2022

Sci Rep

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The directionality between vaccine hesitancy and COVID-19 vaccine side-effects has not been hitherto examined. We hypothesized a nocebo effect, whereby vaccine hesitancy towards the second Pfizer vaccination dose predicts subsequent side-effects for a booster dose, beyond other effects. We expected these nocebo effects to be driven by (mis)information in males and prior experience in females. A representative sample of older adults (n = 756, mean age = 68.9 ± 3.43) were questioned in a typical cross-lagged design (wave 1 following a second Pfizer dose, wave 2 after their booster). As hypothesized, earlier vaccine hesitancy predicted subsequent booster side-effects for females (β = 0.10 p = 0.025, f 2 = 0.02) and males (β = 0.34, p < 0.001, f 2 = 0.16); effects were stronger in males (χ2Δ (1) = 4.34, p = 0.03). The (W1-to-W2) side-effect autoregression was stronger in females (β = .34, p < 0.001; males β = 0.18, p < 0.001), χ2Δ (1) = 26.86, p < 0.001. Results show that a quantifiable and meaningful portion of COVID-19 vaccine side-effects is predicted by vaccine hesitancy, demonstrating that side-effects comprise a psychosomatic nocebo component in vaccinated individuals. The data reveal distinct risk levels for future side-effects, suggesting the need to tailor public health messaging.

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Section: Discussionmentioning

confidence: 84%

Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination

Levin

Palgi

Ben–Ezra

et al. 2022

Sci Rep

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“…Regarding learning trials, we found that increases in both the number of learning and test trials (separately) predicted decreasing nocebo effects. While this was somewhat expected for test trials as a number of studies have shown some evidence of extinction in nocebo effects (Colagiuri et al, 2021; Geuter & Büchel, 2013; Skvortsova et al, 2020; Thomaidou, Veldhuijzen et al, 2021), it was unexpected that increased learning trials would produce smaller nocebo effects. Such a result contradicts virtually everything we know about classical conditioning.…”

Section: Discussionmentioning

confidence: 93%

The nocebo effect across health outcomes: A systematic review and meta-analysis.

Rooney,

Sharpe,

Todd

et al. 2024

Health Psychology

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Objective: The nocebo effect represents a growing concern in clinical settings. Nocebo effects occur when the treatment context generates negative expectancies that trigger the experience or worsening of negative symptoms beyond any effects attributable to the treatment itself. Despite being identified in a range of outcomes and conditions, from pain to Parkinson's disease, there has not been an attempt to systematically quantify the nocebo effects across health outcomes. The purpose of the present review was thus to systematically review and meta-analyze the nocebo literature to quantify the size of the nocebo effect across outcomes and examine which factors moderate the size of the nocebo effect, including process of induction, treatment type, or health outcome. Method: Systematic searches of PubMed, PychInfo, Medline, and Web of Science identified 130 (n = 8,219) independent eligible studies. To be included, studies had to include both a nocebo and control group/condition, which were compared to isolate the nocebo effect size. Results: Overall, the magnitude of the nocebo effect was medium (g = 0.522) and highly heterogeneous. Two key moderators emerged: health outcome and process of induction. Here, the nocebo effect was medium for most somatic outcomes and affect, with no significant effect on worsening cognitive performance. Further, inducing nocebo effects through instruction in combination with conditioning produced larger nocebo effects. Conclusions: The present review suggests nocebo effects can be reliably induced across somatic health outcomes, and interventions that target the effect of instructions will be of critical importance to reducing the occurrence of nocebo effects. Public Significance StatementThis large meta-analysis including more than 100 studies and over 8,000 participants examined nocebo effects across health outcomes. We found a moderately sized nocebo effect (g = 0.522) overall, with strongest nocebo effects for somatic symptoms and when induced by instruction-whether alone or in conjunction with conditioning or social observation. The findings suggest that targeting instructions should be the highest priority for developing strategies to mitigate the enormous personal and societal burden nocebo effects cause, particularly for somatic symptoms.

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“…Third, it would be relevant to compare the efficacy of open-label counterconditioning to the nocebo-preventive strategies. Preliminary findings provide evidence for the efficacy of latent inhibition and overshadowing in inhibiting nocebo effects,54,55 while also contingency degradation is promising 54…”

Section: Discussionmentioning

confidence: 84%

Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction

Karacaoglu

Meijer

Peerdeman

et al. 2023

The Clinical Journal of Pain

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Objectives: The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia and psychological characteristics. Methods: Nocebo effects on pressure pain were first experimentally induced in 83 healthy female participants through conditioning with open-label instructions about the pain-worsening function of a sham TENS device to assess susceptibility to nocebo hyperalgesia. Participants were then randomized to 1 out of 2 nocebo-reduction conditions (counterconditioning/extinction) or to continued nocebo-conditioning (control), each combined with open-label instructions about the new sham device function. Dispositional optimism, trait and state anxiety, pain catastrophizing, fear of pain, and body vigilance were assessed at baseline. Results: The results showed that lower optimism and higher trait anxiety were related to a stronger induction of nocebo hyperalgesia. Moreover, a stronger induction of nocebo hyperalgesia and higher trait anxiety predicted a larger nocebo reduction across interventions. Also, nocebo hyperalgesia and optimism moderated the effects of the nocebo-reduction interventions, whereby larger nocebo hyperalgesia and lower optimism were associated with a larger nocebo reduction after counterconditioning, compared with control, and also extinction for larger nocebo hyperalgesia. Discussion: Our findings suggest that open-label conditioning leads to stronger nocebo hyperalgesia when trait anxiety is high and dispositional optimism is low, while these psychological characteristics, along with larger nocebo hyperalgesia, also predict open-label counterconditioning to be an effective nocebo-reduction strategy. Susceptibility to nocebo hyperalgesia, trait anxiety, and dispositional optimism might be indicators of a flexible pain regulatory system.

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Pre-Exposure, But Not Overshadowing, Inhibits Nocebo Hyperalgesia

Cited by 11 publications

References 49 publications

Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination

Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination

The nocebo effect across health outcomes: A systematic review and meta-analysis.

Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction

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