Mia Thomaidou

182 support the differences found in this study between the High-pain and High-threat groups. Notably, when examining the relationship of pain-related fear with nocebo responses across all three groups, we found that fear reports almost always correlated with the magnitude of nocebo responses. This is interesting, given the substantial interindividual variation in fear of pain 56,57. We further showed that none of the anxiety measures correlated with the magnitude of nocebo responses. This was critical in this study, as we specifically focused on the effects of fear on nocebo hyperalgesia. Fear is a response that is often difficult to disentangle from anxiety, theoretically and physiologically 58,59. The two may produce similar responses, yet involve distinct psychobiological mechanisms, with fear involving more immediate responses to explicit danger, and anxiety presenting as a diffuse response to anticipated threat. Based on our findings, fear, as measured both during and after the experiment, produced larger nocebo responses. In contrast, anxiety, as measured after the experiment and the threat manipulation that involved anticipated threat, was not related to larger nocebo responses. Another method for measuring fear of pain is the measurement of fearpotentiated startle responses. These responses are produced via projections from the central nucleus of the amygdala 60,61. This role of the amygdala, as well as ample fear research, indicate that startle responses may be more specific to fear states and less to states of anxiety 62–64. Average acoustically elicited startle responses range between 100 and 300 microvolts 45,46. Typically, sound probes are delivered via noisecancelling headphones, which achieve optimal auditory conditions and block sounds in the environment 65,66. In this study, earphones were used so that participants could verbally communicate with the researcher, which was crucial in our design. Startle responses were observed; however, potentially as a result of using earphones, these were smaller than expected, on average below 100 microvolts. While trends that

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