Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: A 3T-fMRI study

Visceral pain/discomfort is the cardinal complaints and treatment targets for functional gastrointestinal disorders (FGID). However, effective treatment for such pain is limited and often associated with high placebo effects. The mechanisms of placebo effects in visceral pain are unclear. We used functional neuroimaging to study the central representations of the placebo effect and its anticipation during esophageal pain in healthy adults. Fourteen subjects were enrolled. Pain extent, psychophysical inventories [Pain Catastrophizing Scale (PAS), visual analogue scale (VAS) and short-form McGill questionnaire], and brain activity upon placebo intervention and upon anticipation were assessed in response to esophageal balloon distension. Large reductions of pain extent, VAS rating, short-form McGill questionnaire scores, and brain activity in the visceral pain matrix [thalamus, somatosensory cortices, insula, prefrontal cortex (PFC), anterior cingulate cortex] were observed upon placebo treatment. The aforementioned brain areas and the bilateral amygdala were significantly correlated with decreased pain extent and VAS in response to placebo. The ventral lateral PFC (VLPFC) was associated with increased activity during anticipation of visceral pain. PAS cannot predict the placebo effect in visceral pain. In conclusion, pronounced placebo analgesia was coupled with prominent changes of brain activity in visceral pain matrix, which are thus likely involved in high placebo efficacy during the treatment of visceral pain in FGID. VLPFC activation during the anticipation of placebo analgesia suggests top-down control in the modulation of pain experience.