Chapter 8 – General discussion 273 current understanding of the precise mechanisms that underlie established biobehavioral correlates of nocebo hyperalgesia is still in its infancy. But as growing evidence, discussed in the current dissertation, builds on an explanatory framework for pain aggravation and chronification, the cooperation between negative experiences, cognitive and emotional learning, and sensory integration becomes increasingly relevant for experimental and clinical pain research. Maladaptive learning and emotional factors provide a clinical relevance to the currently known biobehavioral correlates of nocebo hyperalgesia, and have led some to hypothesize that targeted treatments could influence and even reverse the relevant neurobiological aberrances, by addressing learning and emotional dynamics 61. Targeting central components such as aversive learning and fear of pain in patients may help normalize specific brain alterations that underlie learned pain responses. Still, issues of generalizability and ecological validity, as well as a lack in replication of findings within the field, may pose limitations in nocebo research and interpretation. Limitations in the project and the field A central limitation in the neuroscientific nocebo literature, as initially found in chapters 2 and 3, is the widespread inconsistency in methods used and results yielded by experimental research. In this project in particular, while chapter 6 generally confirmed the involvement of intricate learning dynamics in the top-down, cognitive processing of pain signals, it did not replicate specific results of two previous EEG nocebo studies 4,20. Three studies to date, including our own, that have examined the involvement of alpha oscillations in nocebo effects, have found divergent results. Alpha-band neuronal activity has long been implicated in internal cognitive states with low external informational loads 76–79. It is thus likely that different phases and contexts of nocebo
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