258 different brain structures. A follow-up study utilizing fMRI, in chapter 7, attempts to address such limitations. In chapter 7 a novel pharmacological fMRI study examined closely the specific contribution of distinct brain regions and the NMDA receptors that occupy them and facilitate learning. While still utilizing consistent experimental nocebo induction methods for purposes of comparability and reliability within the field, in this study we attempted a pharmacological manipulation of learning during nocebo induction in the MR scanner. We used D-cycloserine, a medication known for its potential to enhance learning through NMDA receptor agonism, to examine whether a group with augmented learning ability would show a larger nocebo response than a group of participants receiving placebo. We found that, despite the pharmacological manipulation not showing any significant behavioral effects, brain regions previously implicated in associative types of learning differentiate nocebo stimuli from control trials. This final neuroimaging study also confirmed results found in chapters 3, 5, and 6 on the emotional correlates of nocebo hyperalgesia, thereby opening the door for future research to focus on district brain plasticity mechanisms as potential driving factors of learned effects on pain. In the general discussion of this thesis, we integrate and interpret the findings of this PhD project in relation to each other and to the broader literature on learned effects on experimental and clinical pain. There are two central findings that arise from the work of this dissertation, both related to the intricate dynamics between nociceptive processing and cognitive-emotional experiential factors. The most central finding, that specific modes of learning shape pain processing in the brain, is discussed as the chief cognitive driver of nocebo hyperalgesia. We discuss how learning is able to alter future pain experiences based on past experience and negative expectations. The second critical finding of this project, that fear-learning may play a mediating role in nocebo
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