Biological and neurodevelopmental implications of neonatal pain.

Nociceptive pathways are functional following birth. In addition to physiological and behavioral responses, neurophysiological measures and neuroimaging evaluate nociceptive pathway function and quantify responses to noxious stimuli in preterm and term neonates. Intensive care and surgery can expose neonates to painful stimuli when the developing nervous system is sensitive to changing input, resulting in persistent impacts into later childhood. Early pain experience has been correlated with increased sensitivity to subsequent painful stimuli, impaired neurodevelopmental outcomes, and structural changes in brain development. Parallel preclinical studies have elucidated underlying mechanisms and evaluate preventive strategies to inform future clinical trials.