Non pharmacological interventions for procedural pain in preterm neonates

描述（由申请人提供）：新生儿重症监护室（NICU）收治的早产儿在住院期间需要进行多达数百次手术。其中许多是已知会引起疼痛的组织损伤程序（TDP）。通过NINR的资助，我们发现TDPs不仅会引起疼痛，还会增加ATP降解和氧化应激的标志物。基于这一发现，我们检查了口服蔗糖的效果，以确定这种常用的镇痛剂是否会降低ATP降解和氧化应激的生化标志物。我们假设，由于口服蔗糖被证明可以显著降低疼痛评分，因此给予这种镇痛药也会降低ATP降解和氧化应激的标志物。然而，我们观察到了相反的效果。虽然单剂量的口服蔗糖减少了疼痛的行为标志物，但随着时间的推移，它显著增加了ATP降解（次黄嘌呤，尿酸）和氧化应激（尿囊素）的生化标志物。更重要的是，口服蔗糖对ATP分解标志物的影响增强，并且在插管或接受超过30%FiO2的新生儿中显著更高。这些发现导致了一个问题：如果口服蔗糖在减少程序性疼痛的生化效应方面无效，那么什么干预或干预组将减少程序性疼痛的行为标志物并减少早产儿的ATP利用率和氧化应激？对于该RO1更新，我们将通过检查两种常用干预措施的个体和累加效应来回答这个问题：（a）30%口服葡萄糖（B）促进卷缩c）30%口服葡萄糖和促进卷缩。这些干预措施是常用的，但它们对细胞生物能量学和氧化应激的影响是未知的。这项研究的结果将为临床医生提供基于证据的干预措施，这些干预措施将减少疼痛的行为体征以及ATP利用和氧化应激的生化标志物。这将为未来的临床试验铺平道路，这些临床试验将研究我们社会中最脆弱的成员预防疼痛和器官损伤之间的关系。

DESCRIPTION (provided by applicant): Premature infants admitted to the neonatal intensive care unit (NICU) require up to several hundred procedures during their hospitalization. Many of these are tissue-damaging procedures (TDPs) known to cause pain. Through funding from NINR, we found that TDPs not only caused pain but also increased markers of ATP degradation and oxidative stress. Based on this finding, we examined the effect of oral sucrose, to determine if this commonly used analgesic reduces biochemical markers of ATP degradation and oxidative stress. We hypothesized that since oral sucrose was documented to significantly reduce pain scores, then administration of this analgesic will also decrease markers of ATP degradation and oxidative stress. However, we observed the opposite effect. Although a single dose of oral sucrose reduced behavioral markers of pain, it significantly increased biochemical markers of ATP degradation (hypoxanthine, uric acid) and oxidative stress (allantoin) over time. More importantly, the effect of oral sucrose on breakdown markers of ATP were enhanced and were significantly higher in neonates that were intubated or were receiving more than 30% FiO2 . These findings lead to the question: If oral sucrose is ineffective in reducing the biochemical effects of procedural pain, what intervention or groups of intervention will decrease both behavioral markers of procedural pain and reduce ATP utilization and oxidative stress in premature neonates? For this RO1 renewal, we will answer this question by examining the individual and additive effects of two commonly used interventions: (a) 30% oral glucose (b) facilitated tucking c) 30% oral glucose and facilitated tucking. These interventions are commonly used but their effects on cellular bioenergetics and oxidative stress is unknown. Findings from this study will provide clinicians with evidence-based interventions that will both decrease behavioral signs of pain and biochemical markers of ATP utilization and oxidative stress. This will lead the way toward future clinical trials that will examine the relationship between prevention of pain and organ injury in the most fragile members of our society.