Fig. 1: Experimental design.

A First, participants were introduced to the same cream, once presented as “Prodicaine, an effective pain-relieving drug” and once presented as “a control cream with no effects”. Then they went through two conditioning phases: (1) A symbolic conditioning phase, in which “ratings of previous participants” were presented for a series of sham pain trials, with ratings systematically higher for the control compared to the placebo skin site. (2) A classical conditioning phase, in which participants experienced a series of thermal stimuli that they thought were random but in fact were experimentally manipulated to be higher for the control compared to the placebo skin site. B Then, the test task took place in the MRI scanner. The task consisted of four runs (order: control, placebo, placebo, control), each including eight trials, four with thermal stimulation and four with mechanical (not conditioned) stimulation. Stimuli in the test task were from three intensity levels per modality. In each trial, participants saw a cue, then experienced the stimulus and rated its intensity and unpleasantness. For further details see “Methods” section. S seconds, Int. intensity, Unp. unpleasantness.