<p>Pain empathy refers to the ability to share and understand pain of others by observing others experiencing pain. Impaired pain empathy has been reported in mental disorders and chronic pain. The neural substrates underlying pain empathy remain poorly understood. We investigated brain activation associated with pain empathy by using functional magnetic resonance imaging (fMRI) following single cathodal transcranial direct current stimulation (tDCS) over the left supramarginal gyrus (SMG) in healthy adults. Twenty-six healthy adults received cathodal or sham tDCS over the left SMG. Task-based fMRI assessed brain activation in cognitive and emotional empathy for pain, and the task performance after tDCS. Self-reported measures of empathy and physical pain assessments were assessed before and after tDCS. The cathodal tDCS decreased activation in the left SMG and right medial frontal gyrus (MedFG) in cognitive empathy for pain. Decreased activation in the right MedFG was positively correlated with the decreased score in cognitive empathy. Furthermore, tDCS among participants with a low level of trait cognitive empathy demonstrated that the decreased activation was associated with the analgesic effect on physical pain. These results suggest the importance of left SMG activation in cognitive empathy for pain in association with the low level of trait cognitive empathy. Our findings may provide information regarding the development of novel intervention in patients with painful conditions originating from the central nervous system.</p>