AR CAREER DEVELOPMENT COBRE: PAIN: EARLY EXPERIENCE AND PRE-ATTENTION MECHANISM

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。早产儿早期反复疼痛，可能导致大脑发育的永久性变化，表现为疼痛处理异常、焦虑增加、认知不良、注意力缺陷障碍以及青春期或成年期的行为问题。新生大鼠反复疼痛与广泛分布的皮质和皮质下区域神经细胞死亡增加有关。青春期后，疼痛暴露的大鼠表现出更大的焦虑、高度警觉、注意力前期和认知缺陷；因此模仿了早产儿的长期行为结果。了解调节这些效应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局。目的1：关键窗口的确定将检验重复性疼痛与最敏感发育阶段神经细胞死亡增加相关的假说(S)。神经元易损性的增加可能在不同的神经解剖学领域受到发育调节，并将与成年大鼠评估的认知和行为结果相关。目的2“细胞死亡机制的研究将验证一个假说，即反复疼痛通过兴奋受体激活导致兴奋性毒性的信号通路而导致神经细胞死亡。减少神经细胞死亡的药物操作将有助于开发新的治疗方法，这也将与成人的认知和行为相关。目标3”对人类注意前过程的评估将检验这一假说，即觉醒调节异常导致青春期或成年期的认知障碍。我们将在早产儿和匹配的早产儿之间比较P50潜能，并将其与他们的注意力任务(精神运动警觉性测试)和执行功能(操作测试电池)的表现以及相对额叶血流量(近红外光谱)相关联。这项拟议的研究旨在将PI确立为独立的临床科学家，并在翻译神经科学中心的主持下进行既定的指导。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 ofpre-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-bom 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 PI as an independent clinician scientist with the help of established mentoring under the auspices of the Center for Translational Neuroscience.