Long-term impact of neonatal injury in male and female rats: Sex differences, mechanisms and clinical implications

Over the last several decades, the relative contribution of early life events to individual disease susceptibility has been explored extensively. Only fairly recently, however, has it become evident that abnormal or excessive nociceptive activity experienced during the perinatal period may permanently alter the normal development of the CNS and influence future responses to somatosensory input. Given the significant rise in the number of premature infants receiving high-technology intensive care over the last 20 years, ex-preterm neonates may be exceedingly vulnerable to the long-term effects of repeated invasive interventions. The present review summarizes available clinical and laboratory findings on the lasting impact of exposure to noxious stimulation during early development, with a focus on the structural and functional alterations in nociceptive circuits, and its sexually dimorphic impact.