Empathetic verbal feedback from others has been shown to alleviate the intensity of experimental pain. To investigate the brain changes associated with this effect, we conducted 3T-fMRI measurements in 30 healthy subjects who received painful thermal stimuli on their left hand while overhearing empathetic, neutral or unempathetic comments, supposedly made by experimenters, via headsets. Only the empathetic comments significantly reduced pain intensity ratings. A whole-brain BOLD analysis revealed that both Empathetic and Unempathetic conditions significantly increased the activation of the right anterior insular and posterior parietal cortices to pain stimuli, while activations in the posterior cingulate cortex and precuneus (PCC/Prec) were significantly stronger during Empathetic compared to Unempathetic condition. BOLD activity increased in the DLPFC in the Empathetic condition and decreased in the PCC/Prec and vmPFC in the Unempathetic condition. In the Empathetic condition only, functional connectivity increased significantly between the vmPFC and the insular cortex. These results suggest that modulation of pain perception by empathetic feedback involves a set of high-order brain regions associated with autobiographical memories and self-awareness, and relies on interactions between such supra-modal structures and key nodes of the pain system