Mia Thomaidou

68 Selection of studies A search strategy was used to identify studies on nocebo hyperalgesia on PubMed and PsychInfo, published up to July 2020, using detailed key terms related to nocebo hyperalgesia, nocebo conditioning, and neurobiological methods (Appendix A). The abstracts of 1761 articles were screened for inclusion by the first author. When there was doubt about inclusion of a study, a decision was made in consultation with the last author. This review focuses only on nocebo hyperalgesia induced in healthy humans, in order to summarize and compare findings that are not influenced by underlying pain or psychological conditions and as such most clearly present the underlying mechanisms of nocebo hyperalgesic effects. Exclusion criteria were: 1) not using an experimental learning paradigm for the induction of nocebo hyperalgesia, 2) not utilizing a healthy human sample 3) not utilizing at least one neurobiological measure, such as brain imaging or a pharmacological manipulation, 4) not inducing significant nocebo responses (as neurobiological responses in relation to nocebo hyperalgesia can only be studied following a successful nocebo manipulation). The articles that fit the inclusion criteria were considered relevant for understanding the neurobiological underpinnings of nocebo hyperalgesia and are described in detail in this narrative review. The final selection included 22 articles (Table 1), of which 6 articles reported electrophysiological measures, 3 focused on chemical correlates, 1 reported structural brain correlates, and 12 reported functional brain correlates using fMRI results. Because we selectively focused on the neurobiology of nocebo hyperalgesia, we report only the nocebo arms of studies (for example, we do not report placebo manipulations). Figure 2 provides an illustration of all major findings of the studies reviewed here.

RkJQdWJsaXNoZXIy MTk4NDMw