Changes

<i>Numerous lines of evidence suggest that even in the human [[fetus]], pain pathways as well as cortical and subcortical centers necessary for pain perception are well developed late in gestation, and the neurochemical systems now known to be associated with pain transmission and modulation are intact and functional. Physiologic responses to painful stimuli have been well documented in neonates of various gestational ages and are reflected in hormonal, metabolic, and cardiorespiratory changes similar to but greater than those observed in adult subjects. Other responses in newborn infants are suggestive of integrated emotional and behavioral responses to pain and are retained in memory long enough to modify subsequent behavior patterns.</i><ref name="anand1987" /> <ref name="vanhowe2008"/>