150 suggestions, and fear-related experiences can alter induced nocebo responses remains unexplored. Pain-related fear may arise as a result of experienced pain or from threatening information regarding upcoming pain. Fear caused directly by experiencing high pain during nocebo conditioning may augment the acquisition of negative expectations. Research indicates that stimuli paired with pain can elicit fear responses 14,20 and such pain-related fear can be acquired through associative learning 21–24. In a more anticipatory fashion, threatening suggestions about potential pain outcomes may also induce pain-related fear which can weigh on future pain experiences and augment nocebo hyperalgesia 25. It is therefore important to determine whether higher reported pain or threatening suggestions amplify nocebo hyperalgesia and whether pain-related fear is a mediator in this putative effect. The study of pain-related fear in nocebo models is an important step towards a comprehensive understanding of nocebo responses. This study aimed to investigate whether high pain intensity or threatening suggestions augment the acquisition and hinder subsequent extinction of nocebo hyperalgesia. We hypothesized that, compared to lower pain, high pain would produce larger nocebo responses and that these would be more resistant to extinction. The same effects were expected for threatening verbal suggestions, compared to the absence of threatening suggestions. We further hypothesized that self-reported and psychophysiological assessments of fear would mediate these effects. Moreover, we explored whether psychological characteristics such as anxiety are related to nocebo magnitudes.
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