Access Type

Open Access Embargo

Date of Award

January 2018

Degree Type


Degree Name




First Advisor

Susanne Brummelte


In the neonatal intensive care unit (NICU) preterm infants are exposed to a multitude of stressors, which include both neonatal pain and reduced maternal care. Clinical and preclinical research has demonstrated that exposure to neonatal pain and reduced maternal care has a profound negative impact on brain and behavioral development. Currently, the biological mechanism by which both of these stressors impacts brain and behavioral outcomes remains widely unknown. To uncover a potential biological mechanism, the current dissertation project utilized a preclinical model of repetitive needle pokes and developed a novel model of reduced maternal care through tea-ball encapsulation. Briefly, rat pups were separated into one of five groups: touch control, isolation and touch, pain, pain and isolation, and unhandled controls. Pups in the isolation conditions were enclosed in tea-ball infusers from postnatal day (PD) 1-4, four times a day for 30 minutes. Pups in pain conditions experienced repetitive needle pokes into alternating paws starting on PD1 and ending on PD4. Unhandled control pups were left undisturbed throughout each experiment. For experiment 1, pups were sacrificed immediately after the last tea-ball exposure on PD4 and serum corticosterone and various brain metabolites were analyzed. We observed a significant increase in serum corticosterone on PD4 in maternally isolated animals and a non-significant increase in pain exposed animals. Further, glutamate/creatine ratios were reduced in the frontal cortex and hippocampus in pain and maternally isolated animals respectively. For experiment 2, pups matured into adulthood and affective and cognitive behaviors were assessed through the open field test, novel object recognition test, Morris water maze, and restraint stress testing. During the Morris water maze, pain exposed animals displayed accelerated learning but both stressors impaired long-term memory. Moreover, reversal learning was enhanced in male isolated animals compared to touch males and isolated females. Finally, female pain exposed animals displayed impaired HPA-axis recovery following an acute stressor. Collectively, these studies demonstrate that both neonatal pain and reduced maternal care are potent neonatal stressors and can influence neonatal neurochemistry and adult cognitive and HPA-axis functioning. These findings highlight the need of interventions mitigating neonatal stress in the NICU.

Available for download on Wednesday, August 07, 2019