• Nicholas J Bush, Jeff Boissoneault, Janelle Letzen, Roland Staud, and Michael E Robinson.
• Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA.
• Eur J Pain. 2023 Sep 1; 27 (8): 102310351023-1035.

BackgroundTask-based functional connectivity (FC) of pain-related regions resulting from expectancy-based placebo induction has yet to be examined, limiting our understanding of regions and networks associated with placebo analgesia.MethodsFifty-five healthy pain-free adults over 18 (M = 22.8 years, SD = 7.75) were recruited (65.5% women; 63.6% non-Hispanic/Latino/a/x; 58.2% White). Participants completed a baseline followed by a placebo session involving the topical application of an inactive cream in the context of an expectancy-enhancing instruction set. Noxious heat stimuli were applied to the thenar eminence of the right palm using an fMRI-safe thermode. Stimulus intensity was individually calibrated to produce pain ratings of approximately 40 on a 100-point visual analogue scale.ResultsA total of 67.3% of the participants showed a reduction in pain intensity in the placebo condition with an average reduction in pain across the whole sample of 12.7%. Expected pain intensity was associated with reported pain intensity in the placebo session (b = 0.32, p = 0.004, R2  = 0.15). Voxel-wise analyses indicated seven clusters with significant activation during noxious heat stimulation at baseline (pFDR  < 0.05). Generalized psychophysiological interaction analysis suggested that placebo-related FC changes between middle frontal gyrus-superior parietal lobule during noxious stimulation were significantly associated with the magnitude of pain reduction (pFDR  < 0.05).ConclusionsResults suggest that stronger expectancy-based placebo responses might be underpinned by greater FC among attentional and somatosensory regions.SignificanceThis article provides support and insight for task-dependent functional connectivity differences related to the magnitude of placebo analgesia. Our findings provide key support that the magnitude of expectation-based placebo response depends on the coupling of regions associated with somatosensory and attentional processing.© 2023 European Pain Federation - EFIC ®.

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