Chapter 1 – General introduction 17 nocebo hyperalgesia can thus be very valuable, next to neurobiological studies that build upon this accumulation of knowledge. Research to date has highlighted some key areas that may be involved in nocebo hyperalgesia. Pain-specific processing has been implicated in the presentation of nocebo hyperalgesic responses. For instance, the dorsal horn of the spinal cord, the secondary somatosensory cortex, and the dorsolateral prefrontal cortex (dlPFC) all seem to be activated during nocebo responses 11,15. This may indicate that pain reports under nocebo hyperalgesic conditions closely resemble typical pain processing. Concurrently, nocebo responses have also been shown to involve brain areas such as the anterior cingulate cortex (ACC), amygdala, and hippocampus 11,69, which supports an involvement of cognitiveemotional factors in nocebo effects, which are also involved in pain processing and integration. Nocebo hyperalgesia also seems to involve chemical systems, such as prostaglandins, cortisol, and dopamine 69,70, while electrophysiological correlates point towards an involvement of alpha and gamma brain rhythms 71–73. It is thus evident, albeit not surprising, that nocebo hyperalgesia largely overlaps with pain processing. The involvement of a wide network of cognitive-emotional processing is also supported by neurophysiological findings. However, replicating findings from one nocebo study to the next seems challenging due to the implementation of diverse experimental models and distinct learning mechanisms between different studies. Employing diverse methods helps clarify specific aspects of nocebo hyperalgesia but also leads to inconsistencies and gaps in the literature, rendering nocebo hyperalgesia a phenomenon that is still poorly understood on a neurocognitive level. With learning and the formation of expectations being at the heart of the most robust nocebo theories 1,11,72,74,75 it is important to observe and interpret similarities between these cognitive processes and nocebo effects. Limbic system structures, and especially the amygdala, are
RkJQdWJsaXNoZXIy MTk4NDMw