The neural mechanisms whereby placebo conditioning leads to placebo
analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo
analgesia. We induced placebo
analgesia by associating a
sham treatment with
pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the
sham treatment, while participants anticipated and experienced brief
laser pain. In the control session participants were explicitly told that the treatment was inactive. The
sham treatment group reported a significant reduction in
pain rating (p=0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo
analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered
pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo
analgesia phases have previously been implicated in placebo
analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of
pain during placebo conditioning that is subsequently maintained during placebo
analgesia.