The Impact of Neonatal Inflammatory Insult on Adult Somatosensory Processing: The Role of the Descending Nociceptive Circuit

The neonatal period represents a critical window of increased neurodevelopmental plasticity in the immature nervous system. Unlike other sensory modalities, which require appropriate stimulation for proper development, maturation of nociceptive circuitry in neonates typically occurs in the absence of noxious stimulation. Premature infants, however, are routinely exposed to multiple invasive medical procedures during neonatal intensive care treatment, which are largely performed in the absence of anesthetics or analgesics. To date, it is largely unknown how exposure to early noxious insult during this time of increased plasticity alters the development of the CNS and influences future nociceptive responses. As previous studies examining the impact of neonatal inflammatory insult on adult nociceptive responses have been conducted primarily in males, the potential adverse effects in females are unknown. Furthermore, the biological mechanisms underlying neonatal insult-induced deficits in nociceptive processing have yet to be elucidated. Therefore, this dissertation addressed the following questions: (1) Does neonatal inflammatory insult differentially alter male and female baseline somatosensory thresholds and response to re-inflammation in adulthood?; (2) Are neonatal inflammation-induced deficits in nociceptive responsiveness mediated by a potentiation in endogenous opioid tone?; and (3) Does pre-emptive morphine analgesia attenuate the behavioral consequences of neonatal inflammatory insult? Collectively, these studies will provide valuable information about the long-term consequences of neonatal noxious stimulation in males and females, which may lead to improved understanding and prevention of the lasting effects of repeated invasive interventions in premature infants in the NICU