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

AR 职业发展 COBRE：痛苦：早期经验和预先注意机制

• 批准号: 7382125
• 负责人: WHIT HALL
• 金额: $ 25.96万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382125
• 关键词: AR; CAREER; DEVELOPMENT; COBRE; PAIN

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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：关键窗口期的确定将检验重复性疼痛与最敏感发育阶段神经元细胞死亡增加相关的假设。神经易损性的增加可能在不同的神经解剖区域受到发育调节，并将与成年大鼠的认知和行为结果评估相关。“对细胞死亡机制的研究将验证重复性疼痛通过激活通过兴奋性受体导致兴奋性毒性的信号通路而导致神经元细胞死亡的假设。减少神经细胞死亡的药理学操作将允许开发新的治疗方法，这也将与成人的认知和行为相关。“对人类注意力前过程的评估将检验唤醒的异常调节导致青春期或成年期认知缺陷的假设。人类觉醒的一种测量方法，P50电位，将在早产儿和足月出生的青少年之间进行比较，并与他们的注意力任务表现（精神运动警惕性测试）和执行功能（操作性测试电池）以及相对额叶血流量（近红外光谱）相关联。拟议的研究旨在将PI建立为一个独立的临床科学家，并在转化神经科学中心的支持下建立指导。