256 mechanisms may give rise to nocebo responses and how this relates to pain outside of the laboratory and in real-world settings. Chapter 4 presents a first experimental study that aimed to demonstrate whether nocebo effects can be induced –and how they may persist– when based on inconsistent and variable learning, more akin to what patients may experience within clinical settings. We compared a typical conditioning paradigm to one with variable reinforcement of the nocebo association between pain and an inert treatment. We also attempted to attenuate the induced nocebo effect to examine the dynamics of different learning schedules over time. While it was unsurprising to find that a more ambiguous learning method led to smaller –albeit significant– nocebo effects, we observed that, interestingly, these smaller effects were more persistent over time, and resisted counterconditioning. This study addressed treatment resistance and chronification of pain relevant to potential experiences in clinical settings and highlighted a role of different types of learning in nocebo hyperalgesia, thereby addressing some of the questions left open in chapters 2 and 3. However, this study did not address the impact of important emotional correlates such as fear, a factor that was not consistently reported in the studies analyzed in chapter 2, but may be implicated in nocebo hyperalgesia. Therefore, in chapter 5, we designed a follow-up experimental study to examine the role of fear in learned pain responses. Despite its known involvement in pain and other clinical outcomes, fear was mostly overlooked by the nocebo field, and our study was the first to manipulate and measure the involvement of different types of fear in nocebo hyperalgesia. Here, we also imaged fear responses, by measuring startle reactions via EMG during a nocebo paradigm. While we retained a typical nocebo induction group as a control, we additionally created one group which would receive higher pain stimulations overall, and another group that received frightful information regarding a potential
RkJQdWJsaXNoZXIy MTk4NDMw