Procedural Pain and Hypoxia in Preterm Neonates

描述（由申请人提供）：入住新生儿重症监护病房（NICU）的患病婴儿平均每天要经历14次痛苦的手术。已知这些手术会改变行为、疼痛敏感性、免疫功能和下丘脑-垂体-肾上腺皮质反应性。此外，有文献记载这些手术会导致心动过缓、全身性低血压和动脉血氧不饱和或“低氧血症”。然而，目前尚不清楚手术相关的低氧血症是否会导致组织缺氧、氧化应激和细胞损伤。这项新的研究者资助申请回应了PA-06-542“疼痛研究的机制、模型、测量和管理（R21）”。我们的长期目标桥梁的特殊利益领域疼痛的早产儿暴露于多种医疗干预和阐明生物行为疼痛的复杂性的优先研究课题。它还借鉴了PI在美国西部最大的跨学科新生儿重症监护中心洛马琳达大学（LLU） NICU担任临床护士/护士经理/临床主任20年的经验，以及她在LLU围产期生物学中心的缺氧博士研究。该项目的目标是开始探索程序疼痛和缺氧之间的关系，以及单一常见NICU程序（如非紧急气管插管）的影响。科学的方法是对早产儿进行前瞻性队列研究。我们的跨学科团队将确定程序性疼痛是否会增加以下内容：疼痛的生物行为标记——早产儿疼痛谱（Specific Aim 1），缺氧的生化标记——ATP分解产物次黄嘌呤、黄嘌呤和尿酸——使用血浆的高效液相色谱法（Specific Aim 2），氧化应激/细胞损伤的生化标记——黄嘌呤氧化酶活性、血浆8-硝基黄嘌呤和血浆丙二醛水平——使用气相色谱/质谱法（Specific Aim 3）。最后，我们将确定程序性疼痛的生物行为标志物与缺氧和氧化应激/细胞损伤的生化标志物之间是否存在正相关（Specific Aim 4）。总之，我们的跨学科团队拥有专业知识，可以将我们的发现应用于我们的工作模型，并开发更好的方法来预防与新生儿疼痛和缺氧相关的长期发病率。入住新生儿重症监护病房（NICU）的患病婴儿平均每天要经历14次痛苦的手术。已知这些手术会改变行为、疼痛敏感性、免疫功能和下丘脑-垂体-肾上腺皮质反应性。此外，有文献记载这些手术会导致心动过缓、全身性低血压和动脉血氧不饱和或“低氧血症”。然而，目前尚不清楚手术相关的低氧血症是否会导致组织缺氧、氧化应激和细胞损伤。这项新的研究者资助申请回应了PA-06-542“疼痛研究的机制、模型、测量和管理（R21）”。我们的长期目标桥梁的特殊利益领域疼痛的早产儿暴露于多种医疗干预和阐明生物行为疼痛的复杂性的优先研究课题。它还借鉴了PI在美国西部最大的跨学科新生儿重症监护中心洛马琳达大学（LLU） NICU担任临床护士/护士经理/临床主任20年的经验，以及她在LLU围产期生物学中心的缺氧博士研究。该项目的目标是开始探索程序疼痛和缺氧之间的关系，以及单一常见NICU程序（如非紧急气管插管）的影响。科学的方法是对早产儿进行前瞻性队列研究。我们的跨学科团队将确定程序性疼痛是否会增加以下内容：疼痛的生物行为标记——早产儿疼痛谱（Specific Aim 1），缺氧的生化标记——ATP分解产物次黄嘌呤、黄嘌呤和尿酸——使用血浆的高效液相色谱法（Specific Aim 2），氧化应激/细胞损伤的生化标记——黄嘌呤氧化酶活性、血浆8-硝基黄嘌呤和血浆丙二醛水平——使用气相色谱/质谱法（Specific Aim 3）。最后，我们将确定程序性疼痛的生物行为标志物与缺氧和氧化应激/细胞损伤的生化标志物之间是否存在正相关（Specific Aim 4）。总之，我们的跨学科团队拥有专业知识，可以将我们的发现应用于我们的工作模型，并开发更好的方法来预防与新生儿疼痛和缺氧相关的长期发病率。

DESCRIPTION (provided by applicant): Sick infants admitted to the neonatal intensive care unit (NICU) are subjected to an average of 14 painful procedures per day. These procedures are known to alter behavior, pain sensitivity, immune function and hypo-thalamic-pituitary-adrenocortical reactivity. In addition, these procedures are documented to result in bradycardia, systemic hypotension and arterial oxygen desaturation or "hypoxemia". However, it is unclear whether procedure-related hypoxemia results in tissue hypoxia, oxidative stress, and cell injury. This new investigator grant application responds to PA-06-542 "Mechanisms, Models, Measurement, & Management in Pain Research (R21)." Our long-term objective bridges the special interest area of pain in preterm neonates exposed to multiple medical interventions and the priority research topic of elucidating the complexity of biobehavioral pain. It also draws on the PI's 20 years of experience as a clinical nurse/nurse manager/clinical director of the Loma Linda University (LLU) NICU, the largest interdisciplinary neonatal intensive care center in the Western United States, and her doctoral research in hypoxia at the LLU Center for Perinatal Biology. The project goal is to begin exploration of the relationship between procedural pain and hypoxia with the effects of a single common NICU procedure such as non- emergent endotracheal intubation. The scientific approach is a prospective cohort study of pre-term neonates. Our interdisciplinary team will determine whether procedural pain increases the following: biobehavioral markers of pain--Premature Infant Pain Profile (Specific Aim 1), biochemical markers of hypoxia--ATP breakdown products hypoxanthine, xanthine, and uric acid--using high performance liquid chromatography (HPLC) of plasma (Specific Aim 2), and biochemical markers of oxidative stress/cell injury--xanthine oxidase activity, plasma 8-nitroxanthine and plasma malondialdehyde levels--using gas chromatography/mass spectroscopy (Specific Aim 3). Lastly, we will determine whether there is a positive correlation between the biobehavioral markers of procedural pain and the biochemical markers of hypoxia and oxidative stress/cell injury (Specific Aim 4). In conclusion, our interdisciplinary team has the expertise to apply our findings to our working model and to the development of better methods for the prevention of long-term morbidity associated with neonatal pain and hypoxia. Sick infants admitted to the neonatal intensive care unit (NICU) are subjected to an average of 14 painful procedures per day. These procedures are known to alter behavior, pain sensitivity, immune function and hypo-thalamic-pituitary-adrenocortical reactivity. In addition, these procedures are documented to result in bradycardia, systemic hypotension and arterial oxygen desaturation or "hypoxemia". However, it is unclear whether procedure-related hypoxemia results in tissue hypoxia, oxidative stress, and cell injury. This new investigator grant application responds to PA-06-542 "Mechanisms, Models, Measurement, & Management in Pain Research (R21)." Our long-term objective bridges the special interest area of pain in preterm neonates exposed to multiple medical interventions and the priority research topic of elucidating the complexity of biobehavioral pain. It also draws on the PI's 20 years of experience as a clinical nurse/nurse manager/clinical director of the Loma Linda University (LLU) NICU, the largest interdisciplinary neonatal intensive care center in the Western United States, and her doctoral research in hypoxia at the LLU Center for Perinatal Biology. The project goal is to begin exploration of the relationship between procedural pain and hypoxia with the effects of a single common NICU procedure such as non- emergent endotracheal intubation. The scientific approach is a prospective cohort study of pre-term neonates. Our interdisciplinary team will determine whether procedural pain increases the following: biobehavioral markers of pain--Premature Infant Pain Profile (Specific Aim 1), biochemical markers of hypoxia--ATP breakdown products hypoxanthine, xanthine, and uric acid--using high performance liquid chromatography (HPLC) of plasma (Specific Aim 2), and biochemical markers of oxidative stress/cell injury--xanthine oxidase activity, plasma 8-nitroxanthine and plasma malondialdehyde levels--using gas chromatography/mass spectroscopy (Specific Aim 3). Lastly, we will determine whether there is a positive correlation between the biobehavioral markers of procedural pain and the biochemical markers of hypoxia and oxidative stress/cell injury (Specific Aim 4). In conclusion, our interdisciplinary team has the expertise to apply our findings to our working model and to the development of better methods for the prevention of long-term morbidity associated with neonatal pain and hypoxia.