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The following is a summary of “Two Sides of Placebo Analgesia: Differential Functional Connectivity Reveals Mechanisms of Placebo Analgesic Response,” published in the January 2025 issue of Pain by Bush et al.
Researchers conducted a retrospective study to explore individual differences in predicting placebo analgesic responses despite previous research on expectancy manipulations.
They recruited 54 healthy, pain-free adults (M=22.8, SD=7.82, 66.7% women) aged over 18. Participants underwent a baseline session followed by a placebo session where an inactive cream was applied with expectancy-enhancing instructions while an fMRI scan was conducted. Painful heat stimuli were applied to the right palm’s thenar eminence, with stimulus intensity calibrated to induce pain ratings of approximately 40 on a 100-point visual analog scale. Generalized psychophysiological interaction (gPPI) was used to assess group differences in functional connectivity during painful versus warmth stimulation.
The results showed 68.5% of participants experienced a 30.3% reduction in pain in the placebo condition, while non-responders had an 18.6% increase in pain. Repeated measures ANOVA revealed a significant interaction between expectancy and responder type (F(1,49)=4.27, P =0.04, ηp2=0.08). Expected pain significantly predicted pain reduction in responders (b=0.37, R2=0.29, P <0.001), but not in non-responders (b=0.11, R2=0.04, P =0.42). The gPPI analysis showed 3 clusters with increased functional connectivity in areas related to attention and sensory integration in placebo responders, while non-responders showed greater connectivity in regions associated with attention and motor processing.
Investigators concluded that the findings demonstrated a distinct behavioral and functional responses to acute pain between individuals who respond and do not respond to placebo analgesia during a pain task.
