PAIN: EARLY EXPERIENCE AND PRE-ATTENTION MECHANISMS

早产婴儿早期的重复性疼痛，并可能导致大脑发育的永久性改变，伴随疼痛处理异常、焦虑增加、认知能力差、注意力缺陷障碍和青春期或成年期的行为问题。新生大鼠重复性疼痛与广泛分布的皮层和皮层下区域神经元细胞死亡增加有关。青春期后，疼痛暴露的大鼠表现出更大的焦虑、过度警觉、注意力前集中和认知缺陷；从而模仿早产儿的长期行为结果。了解介导这些影响的机制可能会导致新的治疗措施，并改善早产的认知和行为结果。目的1：关键窗口的确定将检验假设

Early repetitive pain in premature babies and may lead to permanent changes in brain development, with abnormal pain processing, increased anxiety, poor cognition, attention deficit disorder, and behavioral problems during adolescence or adulthood. Repetitive pain in newborn rats was associated with increased neuronal cell death in widely distributed cortical and subcortical areas. Following puberty, pain-exposed rats showed greater anxiety, hypervigilance, preattentional and cognitive deficits; thus mimicking the long-term behavioral outcomes of ex-preterm children. Understanding the mechanisms mediating these effects may lead to novel therapeutic measures and improve the cognitive and behavioral outcomes of premature birth. Aim 1: Determination of critical windows will test the hypothesis that repetitive pain is associated with increased neuronal cell death during the most sensitive developmental stage(s). Increased neuronal vulnerability may be developmentally regulated in different neuroanatomical areas, and will be correlated with cognitive and behavioral outcomes evaluated in adult rats. Aim 2: Investigation of cell death mechanisms will test the hypothesis that repetitive pain produces neuronal cell death by activating the signaling pathways leading to excitotoxicity via excitatory receptors. Pharmacological manipulations decreasing neuronal cell death will allow the development of novel therapeutic approaches, which will also be correlated with adult cognition and behavior. Aim 3: Assessment of pre-attentional processes in humans will test the hypothesis that abnormal regulation of arousal contributes to the cognitive deficits during adolescence or adulthood. A measure of arousal in humans, the P50 potential, will be compared between adolescents born preterm and matched term-born adolescents, and correlated with their performance of attentional tasks (Psychomotor Vigilance Test) and executive functions (Operant Test Battery), and with relative frontal lobe blood flow (Near Infrared Spectroscopy). The proposed research is designed to establish the Principal Investigator as an independent clinician scientist with the help of established mentoring under the auspices of the Center for Translational Neuroscience.