Chapter 3 – Comprehensive review 85 inhibited activation in the PAG for the nocebo group relative to the control group. Across both groups, the operculum exhibited a gradual decrease in connectivity with the basal ganglia and a gradual increase in connectivity with the STG. However, no differences in connectivity were identified between the nocebo and control groups. The authors suggested that nocebo suggestions may modulate the contribution of the operculum on a pain-transmitting process that involves basal ganglia– thalamocortical loops. Importantly, the nocebo-mediated inhibition of PAG activation suggested that nocebo effects may impede descending pain modulation. Freeman and colleagues (2015) studied negative suggestions regarding a pain-increasing effect of an inert cream labeled “Capsaicin” which was delivered to participants over three experimental sessions. In the first session, pain calibrations were conducted. In the second and third session, baseline pain stimuli were administered at a moderate intensity and short conditioning procedures took place. In the final part of the third session, the evocation phase took place inside the MR scanner. Negative suggestions significantly increased subjective pain ratings. The fMRI results showed that the expectation of increased pain induced significant BOLD activations in the insula, OFC, and PAG. While an involvement of the PAG in nocebo hyperalgesia has been found in previous research (Ellerbrock et al., 2015), it is notable that unlike in Ellerbrock et al. (2015), in this study PAG activation was increased in response to the nocebo manipulation. Jensen and colleagues (2015) aimed to investigate the neural correlates of specifically nonconscious conditioned nocebo hyperalgesia. Participants were told to focus on images presented on a screen that would accompany pain stimulations and to rate their pain following each stimulus. They were then conditioned by use of images that depicted neutral male facial expressions, presented supraliminally. During the subsequent evocation phase, supraliminal and subliminal presentations
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