112 irrespective of the conditioning schedule 15. This indicated that, once established, nocebo hyperalgesia may be especially resistant to extinction; a relevant finding for chronic pain conditions, where learned effects may persist and not become extinct. If extinction is unsuccessful in attenuating these learned effects, a more active approach may be needed to attenuate nocebo hyperalgesia. A promising novel method is counterconditioning. Unlike in extinction, during counterconditioning the negative stimulus is replaced by a more positive stimulus 18. Counterconditioning has recently been successful in different fields 19,20. However, despite its potential as a basis for the treatment of nocebo-augmented pain 21, it remains unclear whether counterconditioning would be an effective intervention for the attenuation of learned nocebo responses. In this study, we compared two nocebo induction methods, conditioning with partial and continuous reinforcement. Furthermore, we examined the consequences of partial versus continuous conditioning for the attenuation of nocebo hyperalgesia via counterconditioning or extinction. We expected to reproduce earlier findings that partial reinforcement would successfully induce nocebo hyperalgesia and that compared to continuous reinforcement, partial reinforcement conditioning would lead to more resistance to extinction. We furthermore examined counterconditioning as a potential attenuation method for nocebo hyperalgesia. The implementation of novel, clinically relevant learning-based methods for investigating nocebo hyperalgesia is an important step towards eventually diminishing nocebo effects in clinical settings.
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