From Relief to Relief and Back Again: Placebo Hypoalgesia Induced by Operant Conditioning with Negative Reinforcement

Operant conditioning has been shown to induce placebo hypoalgesia in experimental settings using verbal, token-based, or social reinforcement. However, in clinical contexts, the most relevant reinforcement appears to be pain relief. This study investigated whether pain relief as reinforcement increases the likelihood of placebo choice and leads to placebo hypoalgesia, while also examining differences between medical and non-medical placebos.Participants were divided into four groups: two experimental (medical and non-medical placebo) and two corresponding controls. During conditioning, pain intensity decreased contingent on placebo choice in experimental groups, whereas in the control groups, pain relief was delivered randomly and was unrelated to placebo choice. In testing, the intensity of all stimuli remained unchanged.Results demonstrated that operant conditioning effectively induced placebo hypoalgesia with the use of both medical and non-medical placebo, as reflected by self-reported pain ratings. However, some differences emerged in response patterns. Unexpectedly, participants in the medical placebo control group chose the placebo more often than those in the experimental group, with no such pattern for the non-medical placebo. Pain expectations shifted over time in the medical placebo experimental group, accompanied by reduced skin conductance amplitude, suggesting physiological changes consistent with hypoalgesia. The placebo effect persisted without extinction particularly in the non-medical placebo group.These findings confirm that pain relief as reinforcement induces placebo hypoalgesia within an operant conditioning framework, highlighting the critical roles of patient agency and reinforcement type in shaping placebo responses, with important implications for optimizing clinical pain management through operant learning mechanisms.