Background & Aims

While previous meta-analyses have included classically conditioned placebo effects [1–4], they often had limited database searches and did not focus solely on classical conditioning. Additionally, they did not take into account the influence of pure conditioning on the magnitude of the placebo/nocebo effect (e.g. studies in which hidden conditioning procedures were used to induce the placebo/nocebo effect, without any verbal suggestions) and did not seek to investigate various factors affecting the placebo effects induced by classical conditioning.?This review aimed to comprehensively analyse placebo hypoalgesia/analgesia and nocebo hyperalgesia induced by classical conditioning, while considering various factors affecting these effects

Methods

PubMed, Cochrane, Embase, PsycINFO, PsycARTICLES, Scopus and Web of Science were systematically searched for relevant publications. Experimental studies published in English, investigating placebo hypoalgesia/analgesia or nocebo hyperalgesia induced by classical conditioning alone or with the addition of other procedures in adult (>18 years of age) healthy volunteers or clinical population were included.

A robust Bayesian random-effects meta-analysis model with weakly informative priors is being used for the meta-analysis. Weakly informative priors are being used to improve identifiability. A heavy-tailed Student’s t distribution with a small number of degrees of freedom is applied to obtain interval estimates of effect heterogeneity.??Additional meta-analyses are being conducted on studies that include the data such as sex and age of the participants.

Results

After the final screening, 25 studies were included in the review. The majority of the studies included participants of both sexes, although some focused exclusively on females. The age range of the participants was between 18 and 53 years. The sample sizes ranged from 20 to 135 individuals. Most of the studies primarily involved healthy volunteers. The primary objective of the majority of the studies was to induce the placebo effect (15), although some aimed to bring on the nocebo effect (5) or both (5). Classical conditioning was successfully used to induce placebo hypoalgesia in 17 cases, and nocebo hyperalgesia in 10 cases. Placebo agents were mostly medically connoted (18), but some research used non-medically connoted alternatives (7). Meta-analyses are still in progress, and their results will be presented during the conference.

Conclusions

Final conclusions will be drawn after the final results of meta-analysis are obtained. However, qualitative data suggests that classical conditioning produces placebo and nocebo effects and contributes to the effects induced by other procedures, including verbal suggestions.

References

1. Blythe JS, Thomaidou MA, Peerdeman KJ, et al. Placebo effects on cutaneous pain and itch: a systematic review and meta-analysis of experimental results and methodology. Pain. 2023;164:1181.
2. Thomaidou MA, Blythe JS, Peerdeman KJ, et al. Learned Nocebo Effects on Cutaneous Sensations of Pain and Itch: A Systematic Review and Meta-analysis of Experimental Behavioral Studies on Healthy Humans. Psychosom Med. 2023;85:308.
3. Vase L, Riley JL, Price DD. A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain. 2002;99:443–52.
4. Petersen GL, Finnerup NB, Colloca L, et al. The magnitude of nocebo effects in pain: a meta-analysis. Pain. 2014;155:1426–34

Presenting Author

Elżbieta A. Bajcar

Poster Authors

Magdalena Zeglen, PhD

MSc, PhD

Institute of Psychology, Jagiellonian University, Kraków, Poland

Lead Author

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Elżbieta A. Bajcar

PhD

Jagiellonian University

Lead Author

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Justyna Braczyk

Jagiellonian University

Lead Author

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Helena Bieniek

Jagiellonian Univeristy

Lead Author

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Boryslaw Paulewicz

MA

Institute of Psychology, Jagiellonian University in Kraków

Lead Author

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Aleksandra Budzisz

MA

Institute of Psychology, Jagiellonian University in Kraków

Lead Author

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Jacek Neckar

MA

Institute of Psychology, Jagiellonian University in Kraków

Lead Author

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Julia Badzinska

Jagiellonian University

Lead Author

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Daryna Rubanets

Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland

Lead Author

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Magdalena Niedbal

MA

Jagiellonian University

Lead Author

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Izabela Laska

Uniwersytet Jagiellonski

Lead Author

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Karolina Wiercioch-Kuzianik

Institute of Psychology, Jagiellonian University in Kraków

Lead Author

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Przemyslaw Bsbel

Prof.

Jagiellonian University, Institute of Psychology, Pain Research Group

Lead Author

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Topics

  • Evidence, Clinical Trials, Systematic Review, Guidelines, and Implementation Science