Chapter 1 – General introduction 11 Nocebo hyperalgesia and its involvement in pain Nocebo hyperalgesia seems to be an intricate component of pain processing. Due to the multifaceted, subjective, and often unpredictable nature of pain, recovery from pain and chronic conditions are especially difficult to manage 13. Pain has been described to arise in response to a nociceptive signal from the body, but this is not always a direct path. Rather, the experience of pain is heavily influenced by an array of processes within the nervous system 14. These intricate processes do not merely rely on information regarding the nature of the nociceptive stimulus, but may include pain processing based on past experiences or cognitive-emotional factors such as fear 13. We start by outlining the basic mechanisms of pain processing, in order to examine how these may be influenced by cognitive and emotional elements under nocebo hyperalgesic conditions. Due to the multifactorial nature of pain, processing of nociceptive input involves a large, distributed neural network that is not yet fully understood 15. Pain pathways have been extensively investigated via neuroimaging methods such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) and are thought to encompass numerous brain regions and processes. One neural system that has been implicated in pain processing relays sensory-discriminatory functions that are mainly involving nociceptive stimulus information. A second, more distributed system, is thought to be involved in cognitiveevaluative processes 16,17 and these could relate to learning and behavioral underlying factors. It should be noted that these networks and systems are not clearly defined, and that the literature contains inconsistencies regarding the exact brain areas that may be included in these systems 17. Nevertheless, sensory-discriminatory processes and cognitive-evaluative processes have been extensively researched and are often found to play important roles in pain perception 16–18 and in nocebo hyperalgesia 19–21.
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