Task-dependent functional connectivity of pain-related brain regions is related to magnitude of placebo analgesia

Previous studies have identified decreases in pain-related activations after placebo induction. However, differences in functional connectivity (FC) of pain-related regions resulting from expectancy-based placebo induction have yet to be examined, limiting our understanding of regions and potential networks associated with placebo analgesia.Thirty-seven healthy adults over the age of 18 (M=21.5, SD =6.3) were recruited (67.6% women). Participants completed a baseline session followed by a placebo session involving topical application of an inactive cream in the context of an expectancy-enhancing instruction set. Painful 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 analog scale (VAS). Functional brain images were collected during each session. Participants rated pain intensity after each scan. Results indicate 76% of the sample showed a reduction in pain intensity in the placebo condition, with an average reduction of 29.6%. Expected pain intensity was associated with reported pain intensity in the placebo session (F(1,34)=12.12, p<.05, R2=.513). Voxelwise analyses indicated six clusters with significant activation during painful heat stimulation at baseline. A similar but attenuated pattern of regions was apparent in the placebo condition. Generalized psychophysiological interaction (gPPI) analysis suggested that placebo-related changes in functional connectivity (FC) between precuneus-hippocampus and middle temporal gyrus-postcentral gyrus during painful stimulation were significantly associated with pain reduction. Taken together, results suggest that changes in FC of memory-related regions involved in pain processing may be an important mechanism underlying placebo analgesia. Title: Brain imaging and pain: analysis of placebo analgesia, Grant Number: R01AT001424.