Neuromodulation Promotes Tissue Regeneration Over Fibrosis
Abstract
Combat injuries sustained by today’s Warfighter are more often than not high-energy injuries from explosions. This results in severe injuries to the areas of the body least protected by body armor, specifically the arms and legs. These high-energy injuries affect multiple body tissues including bone, muscle, and nerve. Often, surgeons who treat extremity injuries focus on the healing of the bone. However, the bone needs overlying muscle to heal and the overlying muscle needs to be healthy so that the limb functions. Both of these tissues, bone and muscle, require nerves that help signal healing processes. The types of signals that nerves in an injured area generate can influence how well or how poorly the bone and muscle tissues heal. This proposed study directly addresses the FY20 PRORP ARA focus area of Retention Strategies by testing how drugs that target nerve signals affect tissue healing. If a medication that helps the healing process can be given to patients with extremity injuries that involved multiple tissues (bone, muscle, nerve, etc.), the healing tissue’s function could also improve. Specifically, decreasing how much tissue scars helps with range of motion and how much strength can be regained with physical therapy. Improved tissue function after injury can then influence a Service member’s opportunity to return to duty. Previous research on U.S. Service members following combat injury has shown that muscle and nerve injury both highly impact return to duty. This research aims to address ways we might improve outcomes for these force-detracting tissue injuries. This study will use two species of mice: one species that does not heal soft tissue injuries well because they form scars and one species that actually is able to regenerate good tissue. We will compare how the “good healer” mouse nerve signals are different from the “bad healer” mouse. We will then use medications that are already clinically available and target the “good healing” nerve signals in a way that may cause the “bad healer” to generate “good healing” nerve signals. By using a medication to adjust the nerve signaling to the injured tissue, we anticipate that the tissue will heal better with less scar. Two specific nerve signals are already planned for this study, but we anticipate that the good healing mouse will show us additional nerve signals that may be targeted by other available medications and/or supplements. While studying mice may seem to be far from helping a human patient, the “good healing” mice are so unique in their ability to regenerate good tissue that they give us an opportunity to learn how their bodies are able to do that. Because the test medications are already safely used to treat nerve-related problems, such as migraine headaches, these research results could be rapidly applied to the next step of research. Ultimately, this research will help map a way to apply these medications in a new way to help extremity-injured patients. By directly addressing the FY20 PRORP ARA focus area of Retention Strategies, this study will benefit current and future Service members who sustain severe extremity injuries and Veterans with combat extremity injuries that are not properly healed. If a safe and effective medication helps the injured tissue heal, the short-term impact is evident. Better tissue healing with less scar will facilitate rehabilitation and function. This could also help Service members return to duty rather than be medically discharged due to their extremity injury. Longer-term impacts include mitigating how poorly healed tissue affects function over a life span. This is positive for both the injured Service members and their families/caregivers who will help see them through the trauma of combat injury and recovery.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110503
Entities
People
- Jennifer Simkin
Organizations
- LSU Health Sciences Center New Orleans
- United States Army