Background & Aims
Placebo hypoalgesia and nocebo hyperalgesia refer to pain decrease and increase, respectively, that occur after administering an inert intervention (a placebo). As placebo hypoalgesia and nocebo hyperalgesia are known to be learning phenomena, it seems essential to study their susceptibility to extinction, i.e. how long the effects last once established. The current systematic review and meta-analysis is the first to summarise and analyse the available data on the extinction of placebo effects in pain shaped by various learning procedures: classical conditioning, operant conditioning, verbal suggestion, and observational learning.
Methods
This systematic review and meta-analysis specifically focus on quantitative data related to extinction but is part of a broader project examining the efficacy of various learning procedures in modifying placebo effects in pain. 7 databases (PubMed, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus, Academic Search Ultimate) were searched. Inclusion criteria comprised 1) enrolled healthy volunteers; 2) placebo or nocebo effects in pain were induced experimentally, 3) extinction, counterconditioning, observational learning, operant conditioning or verbal suggestion were used to change previously induced effects. To investigate the extinction over time, trial-by-trial data from the testing phase (i.e., the phase in which learning effects were tested) were extracted and analyzed. Difference scores were calculated by subtracting the low cue pain rating from the high cue rating (i.e., nocebo – control or control – placebo). Risk of bias was assessed for all the included studies.
Results
25 studies were included in the systematic review with 8 studies on the extinction. Regarding extinction analysis, 2 studies [1, 2] aimed to induce placebo hypoalgesia by observational learning and in 6 studies nocebo hyperalgesia was induced via classical conditioning with verbal suggestion [3-7]. For placebo hypoalgesia, significant differences were found between high and low pain cues in the 1st trial (Mdif = 1.81; CI [1.37, 2.25]) and 2nd trial (Mdif = 1.39; CI [0.63, 2.15]). Differences between high and low cues were insignificant starting from the 3rd trial (Mdif = -0.04; CI [-0.78, 0.70]). Concerning nocebo hyperalgesia, significant differences were observed between high and low pain cues in the 1st trial (Mdif = 0.69; CI [0.69, 0.99]), 2nd trial (Mdif = 0.52; CI [0.28, 0.76]), 3rd trial (Mdif = 0.55; CI [0.18, 0.93]), and 4rth trial (Mdif = 0.41; CI [0.16, 0.67]). Differences between high and low cues were insignificant from the 5th trial (Mdif = 0.03; CI [-0.29, 0.35]).
Conclusions
Placebo hypoalgesia seems to extinguish starting from the third trial, whereas extinction of nocebo hyperalgesia could be indicated starting from the fifth trial. Both placebo hypoalgesia and nocebo hyperalgesia exhibit a trend of extinction over time. Nevertheless, nocebo hyperalgesia seems to be more resistant to extinction as compared to placebo hyperalgesia.
References
[1] Bieniek, H., & B?bel, P. (2022). The Effect of the Model’s Social Status on Placebo Analgesia Induced by Social Observational Learning. Pain Medicine (Malden, Mass.), 23(1), 81–88.
[2] Br?czyk, J., & B?bel, P. (2021). The Role of the Observers’ Perception of a Model’s Self-Confidence in Observationally Induced Placebo Analgesia. The Journal of Pain, 22(12), 1672–1680.
[3] Colagiuri, B., et al. (2021). Pre-Exposure, But Not Overshadowing, Inhibits Nocebo Hyperalgesia. The Journal of Pain, 22(7), 864–
[4] Skvortsova, A., et al. (2020). Effects of Oxytocin on Placebo and Nocebo Effects in a Pain Conditioning Paradigm: A Randomized Controlled Trial. The Journal of Pain, 21(3), 430–439.
[5] Thomaidou, M. A., et al. (2022). A randomized pharmacological fMRI trial investigating D-cycloserine and brain plasticity mechanisms in learned pain responses. Scientific Reports, 12(1), Article 1.
[6] Thomaidou, M. A., et al. (2021). An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia. Pain, 162(1), 287–299.
[7] Thomaidou, M. A., et al. (2020). Learning mechanisms in nocebo hyperalgesia: The role of conditioning and extinction processes. Pain, 161(7), 1597–1608.
Presenting Author
Daryna Rubanets
Poster Authors
Daryna Rubanets
MA
Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
Lead Author
Izabela Laska
Uniwersytet Jagiello?ski
Lead Author
Magdalena ?egle?
PhD
Institute of Psychology, Jagiellonian University, Kraków, Poland
Lead Author
El?bieta A. Bajcar
PhD
Jagiellonian University
Lead Author
Przemys?aw B?bel
Prof.
Jagiellonian University, Institute of Psychology, Pain Research Group
Lead Author
Topics
- Placebo