Nocebo Hyperalgesia, Partial Reinforcement, and Extinction

Abstract

Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result following partial reinforcement. We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (n=135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group only experienced the increase on 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. Partial reinforcement was sufficient to induce nocebo hyperalgesia, however, this was weaker than continuous reinforcement. Interestingly, nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between these and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. As such, partial reinforcement may be one method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence. Perspectives: This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic.