Background & Aims

Conditioning is a well-established mechanism of placebo hypoalgesia and nocebo hyperalgesia (Colloca, 2014). Standard conditioning paradigms and the implementation of instructions create conscious expectations and an awareness for the relationship between the conditioned (CS) and the painful stimuli (i.e., unconditioned stimuli). However, it would be relevant for clinical practice if learning did also take place without conscious expectations. There is some evidence that so-called implicit conditioning using subliminal stimuli as CS is possible (Jensen et al. 2015; Jensen et al. 2012). However, implicit conditioning paradigms with supraliminal presented stimuli are rare. A previous study in that realm induced a conditioned nocebo effect in the perceived unpleasantness of painful stimuli and the skin conductance level (Bräscher et al., 2019). The aim of this study is to replicate the study of Bräscher et al., 2019 with some adjustments and to confirm the results.

Methods

We randomly assigned 144 healthy adults to an experimental and a control group. The differential conditioning paradigm (c.f. Bräscher et al., 2019) consisted of three phases. 1) Acquisition: the cues (symmetric or asymmetric images; counterbalanced) were paired with high and low painful electrical stimuli. The control group received moderate pain stimuli coupled to both cues. 2) Test phase: both cues, CS+ (which was coupled with high painful stimuli in acquisition phase) and CS- (which was coupled with low painful stimuli), were always followed by the moderately painful stimulus in both groups. In both phases, participants rated perceived intensity and unpleasantness after each stimulation. 3) Contingency test phase: no electrical stimuli were applied; only the cues (CS) were shown and participants rated the stimulus intensity and unpleasantness they would expect after these cues in both groups. In addition, we collected tonic and phasic components of electrodermal activity (EDA).

Results

As a prerequisite of successful learning, participants successfully distinguished high and low painful stimuli in the learning phase. We expected that in the test phase the experimental group would show a stronger differential learning effect than the control group and that in the contingency test phase the subjects of both groups would show no differential learning effect, which would indicate that there was no conscious expectation regarding the contingencies. We found no significant interaction effect of group (control vs. experimental), phase (test vs. contingency test) and CS (CS+ vs. CS-) for perceived or expected intensity and unpleasantness. Further, analyses in the experimental group on average showed no differential learning in the test phase. Subgroup analyses of subjects who perceived the stimuli as more painful in CS+ trials than in CS- trials (58% of the experimental group) showed that this is most likely due to a placebo effect.

Conclusions

Our results improve the understanding of implicit learning in the pain domain. The lack of a conditioned effect in the perception of the painful stimulus at the group level may indicate that implicit learning is not well captured by explicit measures, such as asking about perception on a VAS scale. Future studies should investigate subgroup specific characteristics of participants with and without successful differential learning in implicit conditioning experiments.

References

Bräscher, A. K., & Witthöft, M. (2019). Nocebo hyperalgesia induced by implicit conditioning. Journal of Behavior Therapy and Experimental Psychiatry, 64, 106-112. https://doi.org/10.1523/JNEUROSCI.23-10-04315.2003

Colloca, L. (2014). Placebo, nocebo, and learning mechanisms. In F. Benedetti, P. Enck, E. Frisaldi, & M. Schedlowski (Eds.), Placebo. Handbook of Experimental Pharmacology (Vol. 225, pp. 17-35). Springer. https://doi.org/10.1007/978-3-662-44519-8_2

Jensen, K., Kirsch, I., Odmalm, S., Kaptchuk, T. J., & Ingvar, M. (2015). Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness. Proceedings of the National Academy of Sciences, 112(25), 7863-7867. https://doi.org/10.1073/pnas.1504567112

Jensen, K. B., Kaptchuk, T. J., Kirsch, I., Raicek, J., Lindstrom, K. M., Berna, C., Gollub, R. L., Ingvar, M., & Kong, J. (2012). Nonconscious activation of placebo and nocebo pain responses. Proceedings of the National Academy of Sciences, 109(39), 15959-15964. https://doi.org/10.1073/pnas.1202056109

Presenting Author

Lisa Garcia Rodriguez

Poster Authors

Lisa Garcia Rodriguez

MSc

Heinrich Heine University

Lead Author

E-mail

Simon Desch

PhD

Clinical Psychology, Department of Experimental Psychology, Heinrich Heine University Düsseldorf

Lead Author

E-mail

Anne-Kathrin Bräscher

PhD

Department of Clinical Psychology, Psychotherapy, and Experimental Psychopathology, Johannes Gutenbe

Lead Author

E-mail

Susanne Becker

Heinrich Heine University Düsseldorf, Institute of Experimental Psychology

Lead Author

E-mail

Topics

  • Mechanisms: Psychosocial and Biopsychosocial