The purpose of this study is to investigate the modulation of pain responses in the human brain by electric acupoint stimulation (EAS). Eight healthy subjects were enrolled; each received real or mock EAS treatment in separate sessions. Cool (18 degrees C) and cold (2 degrees C) stimuli were delivered, during which functional magnetic resonance imaging scans were performed, before and after treatment. Real EAS specifically increased the pain-specific activation in bilateral secondary somatosensory area, medial prefrontal cortex, and Brodmann area (BA) 32, while it decreased the activation in contralateral primary somatosensory area, BA7, and BA24. We suggest that EAS may induce an analgesic effect via modulation of both the sensory and the emotional aspect of pain processing.