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

测试外用药物减轻糖尿病伤口疼痛和促进愈合的治疗效果

基本信息

批准号：
10261385
负责人：
Miriam N. Weiss
金额：
$ 4.42万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-27 至 2023-09-26
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10261385
关键词：
Address Adult Affect Amputation Angiotensin II Animal Model Area Behavior Biological Blood Blood Pressure Caliber Characteristics Clinical Cytoplasmic Granules Data Data Collection Development Diabetic Foot Diabetic mouse Drug Kinetics Epithelial Exhibits Facial Expression Family suidae Fellowship Fostering Functional disorder Funding Genomics Goals Human Hyperalgesia Impaired healing Individual Individual National Research Service Award Infection Injury Learning Link Losartan Lower Extremity Measurement Measures Mechanics Mediating Methods Miniature Swine Mission Modeling Movement Mus Neonatal Neuropathy Nociception Nociceptive Stimulus Nurses Nursing Research Pain Pain management Pathway interactions Patient-Focused Outcomes Patients Pharmaceutical Preparations Physiology Placebos Postdoctoral Fellow Postoperative Period Process Quality of life Renin-Angiotensin System Reporting Repression Research Research Design Resistance Rodent Role Scientist Signal Pathway Signal Transduction Skin Speed Standardization Stimulus Study models Symptoms Techniques Testing Therapeutic Time Tissues Topical agent Topical application Training Type 2 Angiotensin II Receptor Ulcer United States Universities Variant Venous Withdrawal allodynia behavioral response cost design diabetic diabetic patient diabetic ulcer diabetic wound healing disability efficacy testing experience experimental study foot healing improved infection risk insight interest limb amputation next generation novel pain behavior pain receptor pain reduction pain relief pain sensation porcine model pre-doctoral pressure receptor response skills skin regeneration spontaneous pain tactile display therapeutic effectiveness therapeutic evaluation training project transcriptome sequencing transcriptomics translational model valsartan vocalization wound wound bed wound healing wound treatment

项目摘要

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.

项目概要/摘要申请人请求 NINR Ruth L. Kirschstein 国家研究服务提供五年的支持护理研究个人博士前研究员奖（F31），以检查疼痛和伤口愈合糖尿病溃疡的大型动物模型疼痛且难以愈合的溃疡是一个普遍存在但尚未得到充分研究的问题。糖尿病患者除了感染风险外，还存在明显的疼痛和质量下降。然而，先前的研究表明，使用外用药物可能会改善愈合并减轻疼痛。在这项研究中，我们计划使用具有生物学意义的临床转化大型动物模型。与人类相似，患有糖尿病的小型尤卡坦猪一种新型外用制剂对速度的影响。伤口愈合的质量以及对伤口疼痛刺激的行为反应将被记录下来。实验结束后，将分析组织生物样本和血液以检查转录组变化伤口诱导和治疗之前和之后——其结果可以提供对伤口诱导和治疗之前和之后的机制洞察外用药物对愈合和疼痛行为的影响本研究的目的是检验以下假设：一种应用于伤口的新型外用药剂，将通过改变生物特性来促进愈合并改善疼痛行为我将在两个具体目标上检验这一假设：（1）确定其功效。应用于伤口的局部制剂，以改善伤口愈合并减少疼痛行为，并且 (2) 研究与安慰剂相比，在治疗前和治疗前，用外用药物治疗的伤口的转录组差异在受伤和治疗后，将在愈合过程中测量伤口直径和肉芽。疼痛将通过对机械和热伤害测试的反应来确定。有目的的动作、做鬼脸或发声将被视为疼痛感的有效迹象。对测量自发疼痛行为感兴趣，我将修改成人仔猪鬼脸量表猪伤口的转录组变化将使用下一代 RNA 测序方法进行评估。该培训将使我能够 (1) 发展研究设计、分析和解释领域的技能 (2) 了解疼痛生理学和基因组学的基础知识， (3) 成功通过论文答辩；以及 (4) 获得具有竞争力的长期博士后奖学金；目标是在研究密集型大学成为一名成功的、独立资助的护士科学家。本申请中提出的提案纳入了 NINR 改善患者生活的使命及其研究结果可以增强对伤口愈合和减轻疼痛的科学理解。