92 unsurprising that this broad, primary type of pain processing is involved in nocebo hyperalgesia. Yet, findings that show increased involvement of sensory-discriminatory processes linked to nocebo, as compared to control pain, are very valuable. These findings reveal that typical perception of increased pain stimulation may involve very similar pain mechanisms as aggravated pain under hyperalgesic conditions (i.e., in the absence of increased pain stimulation). Electrophysiological findings showed the important involvement of sensory discrimination. Alpha activity has long been thought to reflect functional blocking of taskirrelevant pathways 83. However, Albu and Meagher’s (2016) findings may point towards an expectation-related inhibition of sensory processing or attention to somatic states, at least on a whole-brain level. Tu et al. (2019) also highlighted a role of alpha band activity, consistently with previous studies showing a clear link between sensory perception and alpha oscillations 84–88. Moreover, Hird and colleagues (2018) found that SPN, an EEG correlate of imminent pain, was related to the nocebo responses, which points to a role of electrophysiological nociceptive processes under hyperalgesic conditions. Biochemical correlates of nocebo hyperalgesia also reflect an involvement of primary sensory processing, although results appear less robust and generally have not been reproduced. Scott and colleagues (2008) demonstrated that nocebo hyperalgesia was characterized by a deactivation of the μ-opioid receptor system, in key nocebo-related brain areas such as the ACC, OFC, insula, amygdala, and PAG. This study further demonstrated that placebo analgesia was characterized by increased activations of the same systems in overlapping brain regions. However, these results should be interpreted with caution because the experimental paradigm did not purposely induce negative expectations, instead, findings are presented for those participants who showed nocebo responses upon a placebo manipulation. In an investigation of the contribution of biochemical correlates of nocebo hyperalgesia in the peripheral nervous system, Benedetti and colleagues (2014) found that
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