Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia.

Przemysław Bąbel,Wacław Adamczyk,Natalia Lisińska,Karolina Świder,Luana Colloca,Paweł Kicman,Elżbieta A Bajcar,Alessio Avenanti

doi:10.1371/journal.pone.0181856

Abstract

The aim of this study was to examine the relationships among classical conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia. A total of 42 healthy volunteers were randomly assigned to three groups: placebo, nocebo, and control. They received 96 electrical stimuli, preceded by either orange or blue lights. A hidden conditioning procedure, in which participants were not informed about the meaning of coloured lights, was performed in the placebo and nocebo groups. Light of one colour was paired with pain stimuli of moderate intensity (control stimuli), and light of the other colour was paired with either nonpainful stimuli (in the placebo group) or painful stimuli of high intensity (in the nocebo group). In the control group, both colour lights were followed by control stimuli of moderate intensity without any conditioning procedure. Participants rated pain intensity, expectancy of pain intensity, and fear. In the testing phase, when both of the coloured lights were followed by identical moderate pain stimuli, we found a significant analgesic effect in the placebo group, and a significant hyperalgesic effect in the nocebo group. Neither expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia. It appears that a hidden conditioning procedure, without any explicit verbal suggestions, elicits placebo and nocebo effects, however we found no evidence that these effects are predicted by either expectancy or fear. These results suggest that classical conditioning may be a distinct mechanism for placebo and nocebo effects.

Highlights

There is a growing body of evidence that classical conditioning can enhance placebo analgesia induced by verbal suggestions [1,2,3,4] and that the effects of classical conditioning on placebo analgesia induced by verbal suggestions are likely to be mediated by expectancies [5,6]
Previous attempts to induce nocebo hyperalgesia by classical conditioning without verbal suggestions have failed [21], the effects of conditioning and verbal suggestions on nocebo hyperalgesia have been found not to be greater than the effects of verbal suggestions alone [21,22]. These results suggest that conditioning, per se, does not significantly increase the nocebo effects induced by verbal suggestions alone
Post-hoc tests revealed that there were no baseline differences in numeric rating scale (NRS) pain ratings for control stimuli across experimental groups, indicating that pain produced by control stimuli was rated among experimental groups

Summary

Introduction

There is a growing body of evidence that classical conditioning can enhance placebo analgesia induced by verbal suggestions [1,2,3,4] and that the effects of classical conditioning on placebo analgesia induced by verbal suggestions are likely to be mediated by expectancies [5,6]. Classical conditioning elicits placebo and nocebo effects

Objectives

Methods

Results

Conclusion