The Prevalence of Neuropathic Pain Pathophysiology Associated with Ankle Fracture
Abstract
This application addresses the FY22 PRMRP Topic Area of Interest of the Chronic Pain Management Research Program. We will utilize subjects who have sustained appendicular fractures and may develop chronic pain following bone union. No attempt will be made to affect the experimental outcome in the subjects. This study will adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of research. Persistent pain following bone fracture, such as neuropathic pain (NP), is a possible outcome of fracture repair following injury to the ankle and exhibits incidence rates at 1-year post-surgery of 18-42%. This pain state following bone healing (also known as bone union) will be referred to as bone fracture-associated NP (BFNP). Ankle fractures are among the most common surgically treated fractures in adults, with the greatest incidence occurring in young, military age males. Women are more commonly affected in other age groups. Full healing from a fracture can take anywhere from several weeks to months. Pain that persists after fracture union has taken place is called chronic pain. Chronic or persistent NP is one of the worst, longest-lasting, and difficult symptom to manage after fracture repair in active duty and retired Veteran populations and civilians. Given the numbers of active duty and Veterans who experience pain due to injury, the U.S. military instituted a number of programs, guidelines, and initiatives to better manage acute pain for combat-related injuries. These programs include pain control methods that can be readily administered and provide pain relief during immediate field hospital care, transport, and subsequent care at military treatment facilities. Despite the instituted practices by the military, BFNP after fracture is a major problem and the literature that documents detailed outcomes of BFNP data are scarce. Chronic bone injury sequelae which may contribute to BFNP include the release of factors that excite and sensitize sensory nerves, enhanced production of pronociceptive neurotransmitters/cytokines/growth factors and receptors, upregulation of sensory neuron ion channels, induction of nerve fiber sprouting in bone tissue, and central sensitization in the brain that amplifies pain. More recent computational approaches suggest that it is also possible that networks of biomarkers exist that could accurately identify individuals at high risk for BFNP that exist at the time of injury and are likely accessible at early time points in fracture care. Changing the standard of care treatment for BFNP by identifying at-risk patients early after injury could lead to decreased economic burden in treating BFNP and mitigation of the substantial decrease in quality of life these patients experience. This proposal directly addresses the focus area of chronification of pain. The proposal will further the understanding of mechanisms underlying the transition from acute to chronic pain following physical trauma, identify risk factors or biomarkers for patients susceptible to pain chronification, and investigate relationships between pain and its co-morbidities that can contribute to the development/progression of chronic pain. Service Members with traumatic injury are disproportionately affected by lost duty days, early retirement, loss of readiness, and increased burden to the Military Health System. The results from these studies will serve as an important step forward in tailoring precision medicine-based treatments to the individual characteristics of each patient for both the prevention and treatment of BFNP in civilian and military populations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311022
Entities
People
- Fletcher White
Organizations
- Indiana University
- United States Army