Electrical low-frequency stimulation (LFS) of nociceptive afferents evokes long-term depression (LTD) of nociception and pain. Information regarding central mechanisms involved in LTD induction and maintenance are still missing. This study hypothesizes that noxious electrical LFS induces changes in activation pattern of pain-related brain areas. Twenty-eight electrophysiological and psychophysical experiments were performed in 14 healthy volunteers. Painful electrical test stimulation (0.125 Hz, 60 pulses) and conditioning LFS (1 Hz, 1200 pulses) were applied by a concentric electrode to the right hand. Test stimulation series were performed before (Pre) and after LFS (Post) or no stimulation period (Control). Volunteers rated pain perception (0 to 100). Somatosensory evoked cortical potentials (SEP) were recorded with 64-channel electroencephalography (EEG). Dipole location, orientation and strength were statistically analyzed for each subject. Pain rating of test stimulation decreased after LFS (-35.3 %, p<0.001). A significant difference in pain perception was shown between Post LFS and Post Control (p<0.01). Topographic distribution of SEP revealed reproducible negative (N2) and positive (P2) components. Source analysis indicated consistent dipolar activity in the anterior and posterior cingulate gyrus (ACC), primary and secondary somatosensory cortex (SI, SII), insula and supplementary motor area. Individual analysis of P2 yielded a significant posterior (p<0.05) shift following LTD induction. Dipole strength analysis showed a significant difference between Post LFS and Post Control for N2 and P2 (p<0.01) whereas dipole orientation remained unchanged. Results demonstrate a shift of cortical activity after LTD induction. Ratings and dipole strength analysis confirm a reduction of pain and nociceptive transmission after LFS. Thus, data reveal central neuroplastic changes of pain processing after LTD induction.