PAIN: EARLY EXPERIENCE AND PRE-ATTENTION MECHANISMS

疼痛：早期体验和预先注意机制

• 批准号: 6972185
• 负责人: WHIT HALL
• 金额: $ 26.44万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-16 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6972185
• 关键词: adolescence (12-20); adult human (21+); arousal; attention; behavior disorders; behavioral /social science research tag; cell death; clinical research; cognition disorders; developmental neurobiology; disease /disorder proneness /risk; early experience; human subject; infrared spectrometry; laboratory rat; longitudinal animal study; longitudinal human study; mature animal; neurons; neurophysiology; outcomes research; pain; pain threshold; premature infant animal; premature infant human; sensory discrimination

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.

早产儿的早期重复性疼痛可能会导致大脑发育的永久性变化，导致青春期或成年期间疼痛处理异常、焦虑增加、认知能力差、注意力缺陷障碍和行为问题。新生大鼠的重复性疼痛与广泛分布的皮质和皮质下区域的神经元细胞死亡增加有关。青春期后，暴露于疼痛的老鼠表现出更大的焦虑、过度警觉、前注意和认知缺陷；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。目标 1：确定关键窗口将检验假设 重复性疼痛与最敏感时期神经元细胞死亡增加有关 发展阶段。神经元脆弱性的增加可能在不同的神经解剖区域受到发育调节，并且与成年大鼠评估的认知和行为结果相关。目标 2：对细胞死亡机制的研究将检验这样的假设：重复性疼痛通过激活信号通路，通过兴奋性受体导致兴奋性毒性，从而导致神经元细胞死亡。减少神经元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。目标 3：对人类前注意过程的评估将检验以下假设：异常的觉醒调节会导致青春期或成年期间的认知缺陷。衡量人类唤醒程度的指标，即 P50 潜力，将在早产青少年和匹配的足月出生青少年之间进行比较，并与他们的注意力任务表现相关联（精神运动警觉测试） 和执行功能（操作测试电池），以及相对额叶血流量（近红外光谱）。拟议的研究旨在在转化神经科学中心的支持下建立指导，使首席研究员成为一名独立的临床科学家。