Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction.

"This study was funded by a VICI grant from the Dutch Research Council (NWO; grant number 45316004), awarded to A.W.M. Evers. The remaining authors have no conflicts of interest to declare."

"This study was funded by a VICI grant from the Dutch Research Council (NWO; grant number 45316004), awarded to A.W.M. Evers. The remaining authors have no conflicts of interest to declare."

"The current research is part of a larger study approved by the Psychology Research Ethics Committee of Leiden University (CEP18-1114/442; pre-registration ICTRP Trial ID: NL8033). In line with the aims of the current research, only a subset of experimental conditions from the larger study was considered for analysis, which entailed the manipulations for inducing and reducing nocebo effects on pressure pain (Fig. ). For further details on all experimental conditions, including the larger study aims and their findings, the readers are referred to a separate publication. Data was used from the same sample, which has a sufficient sample size for conducting the planned analyses of the current research. During the experiment, participants were randomly allocated to a condition where nocebo effects were induced (nocebo conditioning) and subsequently, they were further allocated (1:1:1) to either 1 of the 2 nocebo-reduction conditions, counterconditioning or extinction, or to the control group, continued nocebo conditioning. The idea behind this 2-step design was to create an experimental model that potentially mimics real-life learning events where nocebo effects are induced and then altered by various learning processes. Moreover, in all groups, open-label instructions were provided about the function of a sham TENS device. Open-label instructions were chosen to allow for more ethical implementation of this design as a possible nocebo-reduction strategy for future clinical practice. Findings from open-label placebo studies indicate that an inert treatment can be prescribed without the concealment of their non-pharmacological contents, that is, without deception. Positive treatment outcomes can still be achieved by combining placebo administration with the rationale that placebo mechanisms can lead to the medical improvement of symptoms.– The current experiment applied this open-label rationale to induce and reduce nocebo effects by using a sham TENS device as the inert treatment. As such, participants were informed about the inefficacy of the sham TENS device, that is, in reality, it cannot send electrical signals, but that through expectation mechanisms, the sham activation of the device can lead to either pain in- or a decrease in line with the instructions given about the device."