Chapter 1 – General introduction 19 Figure 2. The working theoretical model of this dissertation. In the process of pain perception, incoming information to the Peripheral Nervous System (PNS) regarding a pain stimulus (bottom-up information), in combination with negative experiences, are influenced by nocebo-related cognitive-emotional factors (top-down information). Based on these factors of interest, integrative processing of pain takes place in the Central Nervous System (CNS), with the potential of giving rise to negative pain outcomes related to learned nocebo responses. The current dissertation In this dissertation, we address biobehavioral aspects of nocebo hyperalgesia, using neuroimaging as well as behavioral science methods. First, a systematic review and meta-analysis provides a novel examination of nocebo effect sizes and relevant factors in experimental studies. Thereafter, a literature review aims to comprehensively summarize what is currently known about the neurobiological correlates of nocebo hyperalgesia. Subsequently, a series of experimental studies attempt to directly manipulate and study cognitive and emotional factors involved in nocebo, by use of innovative methods. Fear and pharmacological manipulations of specific learning mechanisms are utilized for the first time in these studies, while original 3DLQ VWLPXODWLRQ LQFRPLQJ WR 316 1HJDWLYH H[SHULHQFHV DVVRFLDWHG WR SDLQ )HDU ([SHFWDWLRQV %HOLHIV 3DLQ FRJQLWLYH SURFHVVLQJ LQWHJUDWLRQ LQ &16 3DLQ RXWFRPH H[SHULHQFHG SDLQ ,QFRPLQJ LQIRUPDWLRQ &RJQLWLYH HPRWLRQDO FRPSRQHQWV %LREHKDYLRUDO LQWHJUDWLRQ 3DLQ SHUFHSWLRQ &KDSWHUV &KDSWHUV &KDSWHUV &KDSWHUV /HDUQLQJ
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