Rewarded placebo analgesia: A new mechanism of placebo effects based on operant conditioning.

Background: Placebo analgesia is explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. We aimed to induce placebo analgesia by operant conditioning.

Methods: Three groups of participants received electrocutaneous pain stimuli of the same intensity, preceded by either an orange or blue stimulus. In the conditioning phase of the study, participants from the experimental group were rewarded for low pain responses following one of the colour stimuli (placebo) and for high pain responses following the other colour stimuli (non-placebo). Moreover, they were punished when their pain responses were high following placebo stimuli and low following non-placebo stimuli. To investigate the role of contingency, that is dependent relation between rewards/punishers and pain responses, the random-control group received rewards and punishers in a non-contingent manner. The colour-control group did not receive any rewards or punishers to control for nonassociative learning. Pain intensity ratings were used as an outcome measure, and verbal feedback on pain ratings was used as rewards/punishers.

Results: When rewarding and punishment were stopped, only participants from the experimental group experienced less pain following the placebo than following the non-placebo stimuli; that is, placebo analgesia was found in this group. This effect was not extinguished during the study.

Conclusions: Placebo analgesia can be induced by operant conditioning, which should be considered a third mechanism for producing placebo effects. Moreover, the contingency between pain responses and rewards/punishers is crucial to induce placebo analgesia through operant conditioning.

Significance: According to the current placebo literature, placebo analgesia can be explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. Our study reveals that patients can learn placebo analgesia as a result of operant conditioning, suggesting that randomized controlled trials could be improved by controlling the reinforcement that might occur spontaneously when patients interact with, for example, medical personnel.