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

点击翻译按钮获取中文摘要

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.