While animal studies suggest that neonatal pain experiences induce long-term alterations in pain sensitivity, no such data exist in humans. Changes in pain sensitivity in school-aged children (9-14 years) who were born preterm or fullterm, had been hospitalized for a prolonged period of time after birth and had undergone repeated painful procedures while being treated in a Neonatal Intensive Care Unit (NICU) were determined. A retrospective cohort study of 19 preterm (<or=31 weeks gestational age) and 20 fullterm children (>or=37 weeks gestational age) treated at least 3 days in a NICU at a University Hospital and 20 fullterm control children without NICU experience was performed. Perceptual sensitization to tonic heat and repetitive mechanical stimuli as well as heat pain and mechanical pain thresholds were obtained at the thenar and a trigeminal site. Length of hospitalization and NICU treatment was significantly higher in preterm than fullterm children. Nonetheless, both preterm and fullterm children with NICU experience showed greater perceptual sensitization to tonic heat and elevated heat pain thresholds at both sites. Mechanical pain threshold and perceptual sensitization did not differ between groups. Consistent with findings in animals, repeated pain experiences during the neonatal period were associated with alterations in thermal pain responsivity in school-aged preterm and fullterm children that was characterized by enhanced perceptual sensitization to prolonged painful stimulation and hypoalgesia to brief heat pain stimuli. Our findings suggest that repeated pain experiences in neonates may induce activity-induced changes in the functioning of pain pathways that persist well beyond infancy.