How negative experiences influence the brain in pain: neuroimaging and biobehavioral insights

Abstract

This PhD research dealt with neurobiological and behavioral aspects of pain. Previous research has demonstrated that pain sensitivity can be worsened as a result of learned negative expectations, a phenomenon termed nocebo hyperalgesia –a counterpart to placebo analgesia. This PhD dissertation describes neuroimaging and biobehavioral experimental studies as well as a review and a meta-analysis concerned with such learned effects on pain. The research adds to a growing literature that has been challenging antiquated understandings of pain as a bottom-up process. We conducted a series of biobehavioral studies to further our understanding of how bottom-up pain signaling can be influenced by top-down processing. We examined the types of experiences, such as receiving negative information or experiencing a negative effect first-hand, that may lead to stronger nocebo effects. Behavioral paradigms were used to model real-life pain experiences, through validated methods, novel learning manipulations, as well as a close examination of emotional correlates such as fear. Concurrently, innovative neuroscientific methods –including pharmacological manipulations– were used to examine the biobehavioral underpinnings of learned nocebo 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.