Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive
analgesics and/or
anesthesia are administered less than 25% of the time. Unalleviated
pain during the perinatal period is associated with permanent decreases in
pain sensitivity, blunted
cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and
pain behavior occur, and whether such alterations can be prevented by appropriate
analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life
pain suggests that inflammatory
pain experienced on the day of birth blunts adult responses to stress- and
pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous
opioid tone. This review focuses on the long-term impact of neonatal inflammatory
pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous
pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of
analgesia/
anesthetic use for early life
pain in the modern NICU.