Chapter 3 – Comprehensive review 83 The authors stated that this difference indicated that negative expectations in combination with high pain stimulation elicited a sum of neural activity that enhanced activation of afferent pain circuitry. In the context of descending pain modulation, expectation and pain intensity may have acted in an additive manner on afferent pathways when these were activated by high pain stimulation. Kong and colleagues (2008) informed their participants that a (sham) acupuncture treatment on the arm may increase their pain sensitivity while also conditioning them with surreptitiously increased thermal pain stimulations. During the fMRI session, participants underwent the nocebo manipulation again and then received all pain stimulations at moderate intensity. After administering the inert treatment, pain intensity ratings significantly increased for the nocebo sites compared to control sites on the arm. Pre- and post-treatment differences in brain activations revealed significant increases in activations during nocebo, as compared to control trials, in the dorsal ACC, insula, Superior Temporal Gyrus (STG), left frontal and parietal operculum, medial frontal gyrus, OFC, superior parietal lobule, hippocampus, right putamen, lateral PFC, and middle temporal gyrus (MTG). Furthermore, significant positive correlations were observed between nocebo magnitudes and activations in the bilateral insula and left primary motor cortex. Significant negative correlations were observed between nocebo magnitudes and activations in the dlPFC and left OFC. Activation differences in these brain regions suggest that nocebo hyperalgesia predominantly engaged the affectivecognitive pain circuit. In a later study, Kong and colleagues (2013) studied pain expectations but now without employing a sham treatment. In this fMRI study, visual cues were associated with high thermal pain stimulations. When predictive cues were paired with moderate pain intensity, nocebo hyperalgesic responses were reported. fMRI data from the evocation of nocebo hyperalgesia did not yield major findings related to the
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