AR CAREER DEVELOPMENT COBRE: PREVENTING THE LONG-TERM NEONATAL PAIN

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 新生儿疼痛的影响可能会导致持续到成年的生理、激素和行为反应，并可能导致常规药物难以治愈的功能障碍。减少新生儿疼痛影响的治疗方法还没有得到充分的研究，现有的治疗方法被随意使用。因此，需要有效的疼痛管理和低副作用的预防性干预。这些先发制人的技术包括与新生儿的皮肤接触(袋鼠护理)、促进折叠和哺乳糖衣奶嘴。在这一应用中，我们建议评估先发制人护理预防新生儿疼痛长期后果的有效性和作用机制。假设先发制人的新生儿干预将减少与痛苦的新生儿手术相关的压力反应，也将减少以后生活中的不良后果。为了验证这一假说，我们首先建议检验在受伤时进行的新生儿拥抱(NC)是否可以预防成年大鼠新生儿结肠炎/疼痛的长期影响。其次，我们将展示新生儿拥抱(袋鼠护理)将对新生儿重症监护病房(NICU)婴儿的健康护理结果产生积极影响。无论是在人类还是动物模型中，这些先发制人的措施减少暴露在痛苦/压力下的新生儿程序的成年人的长期后果的能力都没有被研究过。为了检验这一中心假设，我们设计了三个具体目标。在具体目标1中，将进行行为学研究，以表明NC通过减少与新生儿损伤相关的应激，防止成年大鼠新生结肠刺激的长期内脏高敏感性的发展。在具体目标2中，将在NICU测试袋鼠护理等减压技术，以评估它们对病情稳定的早产儿的好处。在一些临床和基础研究中，新生儿创伤的长期后果一再被证明对个人有害。这些研究强调，迫切需要在临床环境中开发新的先发制人的护理方法，以减少新生儿创伤的影响。这项建议汇集了一支由基础和临床科学家组成的团队，他们既有成熟的，也有正在接受培训的，以评估减压技术对新生儿创伤后果的影响。提出的研究集中在一个中心假设上，将在实验室和临床上进行测试，并强调研究人员之间的高度协同。如果成功，这些研究将使我们能够产生足够的额外数据来扩大这项提议的范围，并开发多研究者R01的应用。此外，这些结果应该对新生儿护理产生积极影响，并减少暴露在新生儿疼痛和压力下的成年人的长期后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The effects of neonatal pain may result in physiological, hormonal and behavioral reactions that persist into adulthood and may cause functional disorders that are refractory to conventional medicine. Treatments to decrease the effects of neonatal pain have not been adequately researched and existing ones are used capriciously. Therefore, effective pain management and pre-emptive interventions with low side effect profiles are needed. These pre-emptive techniques include skin-to-skin contact with the neonate (kangaroo care), facilitated tucking and suckling sugar-coated pacifiers. In this application, we propose to evaluate the effectiveness and mechanism of action of pre-emptive care to prevent long-term consequences of neonatal pain. The hypothesis is that pre-emptive neonatal interventions that will decrease stress responses associated with painful neonatal procedures will also decrease adverse consequences later in life. To test this hypothesis, we first propose to examine whether neonatal cuddling (NC) around the time of injury can prevent the long-term effect of neonatal colon inflammation/pain in the adult rat. Second, we will show that neonatal cuddling (kangaroo care) will positively impact the health care outcomes of babies in the neonatal intensive care unit (NICU). The ability of these pre-emptive measures to reduce the long-term consequences in adults who were exposed to painful/stressful neonatal procedures has not been studied in either humans or animal models. To test the central hypothesis, three specific aims were designed. In specific aim 1, behavioral studies will be conducted to show that NC prevents the development of long-term visceral hypersensitivity in the adult rat with neonatal colon irritation, by reducing the stress associated with neonatal injury. In specific aim 2, stress-reduction techniques such as kangaroo care will be tested in the NICU to evaluate their benefits to premature infants who are in stable condition. The long-term consequences of neonatal trauma have been shown repeatedly to be detrimental to the individual in a number of clinical and basic studies. These studies have emphasized the immediate need to develop new preemptive care approaches in the clinical setting to lessen the impact of neonatal trauma. This proposal brings together a team of basic and clinical scientists, both established and in training, to evaluate the impact of stress-reduction techniques on the consequences of neonatal trauma. The studies proposed focus on one central hypothesis that will be tested in the laboratory and the clinic and highlight the high level of synergy among the investigators. If successful, these studies will enable us to generate additional data sufficient to broaden the scope of this proposal and to develop a multi-investigator R01 application. Furthermore, the results should have a positive impact on neonatal care and decrease long-term consequences in adults who were exposed to neonatal pain and stress.