Preterm infants undergo several painful procedures in the neonatal intensive care unit, which in the long-term can have undesirable consequences. These early nociceptive insults occur at a critical time during development. We think that painful procedures early in life can alter the development of the children's endogenous pain control mechanisms and lead to differences in the modulation of pain perception during adolescence. We tested this hypothesis by measuring the pain threshold, pain sensitivity and pain modulatory mechanisms in children between the age of 12 and 18 years which were either born prematurely (n = 17) or at term (n = 14). Pain threshold was measured by using a thermode; pain sensitivity was measured using a temporal summation paradigm (i.e., 2 min. thermode stimulation at constant temperature on the forearm). The sensitivity was evaluated before and after having recruited the activity of the endogenous pain modulatory system (DNIC). DNIC was triggered by the immersion of the arm in cold water (10ºC). Analyses showed that, for all pain scores, preterm children did not differ from full term children. However, when the preterm group was further divided as a function of the extent of pain experienced at birth, only the group exposed to less noxious insult at birth had an significant DNIC response (p<0,05). There were no significant differences between the groups with respect to autonomic reactivity, however there was a trend toward a higher sympathetic activity for the preterm group. These results show that preterm children are not hyperalgesic, but that their pain modulatory mechanisms are not well developed when they are exposed to numerous painful procedures at birth.