262 Complex sensory phenomena such as nocebo hyperalgesia, that may implicate diverse cognitive processes, are thus very difficult to investigate reliably based on influenceable and volatile scores obtained through self-report. While self-report is the most accurate measure of subjective pain experiences that we currently have, in order to gain a comprehensive picture of learned effects on pain, there is a need for directly measuring biobehavioral factors under nocebo hyperalgesic conditions. This closer look into the neurobiology of nocebo effects is of high importance given the convolution, subjectivity, and potential inter- and intra-individual variability of experienced pain. Despite the important takeaways provided by our comprehensive summary of the neurobiological nocebo literature, widespread inconsistencies in findings are also shown and we discuss this as a worrying trend to be addressed in future research. The utilization of distinct learning paradigms for inducing nocebo hyperalgesia may influence neurobiological findings. In other fields of research, such as in the domains of learning and memory, different types of learning have been shown to employ different brain processes, with complex architectures underlying distinct learning systems 6–9. Concurrently, differences in emotional load, frightfulness of negative suggestions 10,11, or even the magnitude of induced hyperalgesia 12, may influence the neurobiological processes that are involved in nocebo responses. For these reasons, it is important for the nocebo field to begin employing more consistent methods and pursue replication of studies, in order to achieve reliable and meaningful findings. In the experimental parts of this project, we conformed with this recommendation, using validated and consistent experimental models for nocebo induction, while also implementing novel aspects.
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