Testing the therapeutic effectiveness of a topical agent to reduce diabetic wound pain and improve healing

项目摘要/摘要 申请者要求NINR Ruth L.Kirschstein国家研究服务机构提供五年的支持 护理研究个人博士前研究员奖(F31)，用于检查患者的疼痛和伤口愈合情况 糖尿病溃疡的大型动物模型。疼痛和愈合不良的溃疡是一个普遍存在的问题，但研究不足。 在糖尿病患者中。除了感染的风险，还会有明显的疼痛和质量下降 与他们相关的生活。使用外用药物可能会促进愈合并减轻疼痛；然而，先前的研究 已经显示出有限的好处。在这项研究中，我们计划使用临床平移的大型动物模型和生物学 与人类相似的是糖尿病微型尤卡坦猪。一种新型局部用药对速度的影响 伤口愈合的质量，以及对伤口疼痛刺激的行为反应，都将被记录下来。 实验结束后，将对组织生物标本和血液进行分析，以检查转录变化。 在伤口诱导和治疗前后-其结果可以提供对创伤诱导和治疗的机械性洞察 外用药物对愈合和疼痛行为的影响。这项研究的目标是检验这一假设 一种新的外用剂，应用于伤口，将通过改变生物变化来促进愈合和改善疼痛行为。 伤口床上的信号通路。我将在两个具体目标上检验这一假设：(1)确定 一种外用药剂，应用于伤口，以促进伤口愈合和减少疼痛行为和(2)调查 与安慰剂相比，外用药物治疗的伤口在治疗前和治疗后的转录差异 在受伤和治疗之后。伤口直径和肉芽组织将在愈合过程中测量。 进程。疼痛将通过对机械和热敏测试的反应来确定。任何提款， 有目的的动作、鬼脸或发声将被认为是痛感的有效迹象。既然我是 对自发疼痛行为的测量感兴趣，我将为成人修改仔猪做鬼脸量表 猪。伤口中的转录变化将使用下一代RNA测序方法进行评估。 这项培训将使我能够(1)发展研究设计、分析和口译方面的技能 临床翻译的大型动物模型；(2)了解疼痛生理学和基因组学的基本原理， (3)成功答辩；(4)获得竞争激烈的博士后长期奖学金 目标是在一所研究密集型大学成为一名成功的、独立资助的护士科学家。这个 本申请中提出的建议包含了NINR改善患者生活的使命及其调查结果 可能会增强对伤口愈合和减轻疼痛的科学理解。

PROJECT SUMMARY/ABSTRACT The applicant is requesting five years of support from a NINR Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows in Nursing Research (F31) to examine pain and wound healing in a large animal model of diabetic ulcers. Painful and poorly-healing ulcers are a prevalent, yet understudied issue among diabetic patients. In addition to risk for infection, there is also significant pain and decreased quality of life associated with them. Use of a topical agent may improve healing and reduce pain; however, prior research has shown limited benefit. In this study, we plan to use a clinically translational, large animal model with biological similarities to humans, the diabetic miniature Yucatan swine. The effects of a novel topical agent on the speed and quality of wound healing, as well as the behavioral response to wound pain stimuli, will be documented. Following the experiment, tissue biospecimens and blood will be analyzed to examine transcriptomic changes before and after wound induction and treatment—the results of which could provide mechanistic insight into the effects of the topical agent on healing and pain behavior. The goal of this research is to test the hypothesis that a novel topical agent, applied to wounds, will improve healing and improve pain behavior by altering biological signaling pathways in the wound bed. I will test this hypothesis in two specific aims: (1) determine the efficacy of a topical agent, applied to wounds, to improve wound healing and reduce pain behavior and (2) investigate transcriptomic differences in wounds treated with the topical agent, as compared to placebo, prior to and following injury and treatment. Wound diameter and granulation will be measured during the course of the healing process. Pain will be determined using responses to mechanical and thermal nocifensive testing. Any withdrawal, purposeful movement, grimacing, or vocalizations will be considered a valid sign of pain sensation. Since I am interested in measurement of spontaneous pain behaviors, I will modify the piglet Pig Grimace Scale for adult pigs. Transcriptomic changes in the wound will be evaluated using next-generation RNA sequencing methods. This training will allow me to (1) develop skills in the areas of research design, analysis and interpretation using a clinically translational large animal model; (2) learn about the fundamentals of pain physiology and genomics, (3) successfully defend a dissertation; and (4) obtain a competitive post-doctoral fellowship with the long-term goal to become a successful, independently-funded nurse scientist at a research-intensive university. The proposal presented in this application incorporates the NINR mission of improving patient lives and its findings may enhance scientific understanding of wound healing and pain reduction.