Chapter 8 – General discussion 279 pain processing. Yet, three decades of research into nocebo hyperalgesia have also provided us with important and clinically relevant insights into the detrimental effect of learning on pain experiences. The early knowledge that nocebo research has generated for clinical practice should not be underestimated. It is consistently shown that contextual experiences and communication of negative outcomes can shape the way in which individuals experience pain 12,92–96. In this dissertation, we additionally showed that fear of pain as well as individuals’ physiological learning patterns and baseline brain dynamics can further facilitate negative pain associations resulting in increased pain sensitivity. The phenomenon of pain can thus be seen as a system that, prior to conscious pain perception, engages in the top-down cognitive and often emotional processing of ascending noxious stimuli, giving rise to an inherently subjective pain experience. This PhD project supported and expanded upon previous work on nocebo effects, showing that learning and fear play key roles in this top-down processing of pain. In the clinic, these findings could be applied to defuse those factors that we now know to reinforce negative associations, such as negative suggestions by healthcare professionals, contextual triggers of negative associations, traumatic pain experiences, uncertainty, and fear. From the clinical perspective our finding that counterconditioning was more effective than extinction in minimizing nocebo responses may also open avenues for behavioral treatments for pain symptoms that may be aggravated by learning. Conclusions Negative experiences influence the brain and can decidedly alter the experience of pain. Past experience appears to shape future experience. This PhD dissertation focused on enriching our understanding of negative learned effects on pain by investigating nocebo hyperalgesic
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