254 Summary This thesis adds to a growing literature that has been challenging antiquated understandings of pain as a bottom-up process. In this project, we conducted a series of biobehavioral studies to further our understanding of how bottom-up pain signaling can be influenced by the top-down processing that may often be involved in pain. We employed diverse methodologies, such as a large-scale meta-analysis, a comprehensive review, behavioral experimental studies, as well as experiments utilizing imaging techniques such as fMRI, EEG, and EMG. We examined the types of experiences, such as receiving negative information or experiencing a negative effect first-hand, that may lead to stronger or more persistent nocebo effects on pain. We furthermore aimed to unravel underlying biobehavioral components of such learned pain responses. Behavioral paradigms were used to model real-life pain experiences, through validated experimental pain induction methods, novel experimental learning manipulations, as well as a close examination of emotional correlates such as fear. Concurrently, diverse, innovative neuroscientific methods –including a pharmacological manipulation– were used to examine the biobehavioral underpinnings of nocebo hyperalgesic responses. Our findings add to the growing knowledgebase from the field of nocebo hyperalgesia, demonstrating that learning by experience can decisively influence the processing and perception of noxious stimuli. In chapter 2, a systematic review and meta-analysis indicated that learning by experience is a potent mechanism that can influence the perception and persistence of pain. Building upon the past two decades of proliferation in nocebo research, this comprehensive meta-analysis delivers novel insights into the currently known behavioral correlates and pain outcomes under nocebo hyperalgesic conditions. Classical
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