The present study investigated the influence of short-term horizontal body position on pain-related somatosensory processing, by measuring subjective and cortical responses to electrical pain stimulation. Twenty-eight healthy women were randomly assigned to either the experimental horizontal group (Bed Rest, BR) or to the sitting control group (Sitting Control, SC). After 90 minutes in either horizontal or sitting position, the individual pain thresholds were assessed and EEG/self-evaluations recorded during the administration of 180 stimuli delivered to the left forearm. Electrical pain stimuli, calibrated to subjects’ individual pain thresholds, consisted of two different intensity levels: no pain (40% below pain threshold) and pain (40% above pain threshold). Compared with control, BR condition significantly inhibited subjective sensitivity to painless stimuli, whereas electrophysiological results pointed to a reduced slow cortical wave (interval: 300-600 ms) at all stimulus intensities, and smaller amplitude in BR’s right vs. left prefrontal sites. sLORETA analysis revealed that cortical responses were associated with a decreased activation of superior frontal gyrus and anterior cingulate cortex (BA 6/24). Interestingly, BR group only showed significant negative correlations between self-evaluation of painful intensities and frontal cortical negativity, revealing increasingly differentiated responses in bed rest: indeed those BR participants who reported lower pain ratings, displayed reduced negativity within anterior regions. Taken together, results indicate that short-term horizontal position is able to inhibit a fronto-parietal pain network, particularly at the level of central prefrontal regions typically involved in cognitive, affective and motor aspects of pain processing.