Chapter 3 – Comprehensive review 95 Concurrently, the spinal cord has also been found to interact with higher-order areas such as the PAG in nocebo hyperalgesia 62,63. Pain modulation may thus involve an interconnected and wide-spread circuit, with nocebo studies showing both afferent pain amplification under nocebo conditions and efferent pain modulation 62,63. This highlights a role of the entire pain system, from physiological nociceptive signaling in the spinal cord all the way to cognitive modulatory processing in the brain in nocebo hyperalgesia. Learning leading to expectations Since the formation of negative expectations through learning lays at the core of nocebo hyperalgesia, it is unsurprising that cognitive modulation was found to be an important factor in nocebo hyperalgesia. MEG findings implicated alpha band connectivity between the rACC and MTG, which may reflect a process in which experience might be encoded through the dynamics of neural networks 96,97. Concurrently, analyses of EEG biomarkers (Thomaidou et al., 2021a) indicated a main involvement of long-range temporal correlations of brain oscillations as well as gamma band activity, both of which have previously been linked to learning 98–100. These electrophysiological findings connect nocebo hyperalgesia to learning processes that can be reflected through electrophysiological components. Time-sensitive responses to nocebo hyperalgesia were studied through ERPs, which also highlighted the role of pain expectation. The reduction in N2/P2 amplitudes that was found by Pazzaglia and colleagues (2016), as well as the involvement of SPN found in Hird and colleagues, are linked to the predictability and temporal expectations of nociceptive stimuli 101,102, supporting the notion that nocebo effects are reliant on pain expectations. On the other hand, the finding of CNV differentiation between placebo and nocebo effects also highlighted the role of expectations, but additionally
RkJQdWJsaXNoZXIy MTk4NDMw