# Developing Novel Models for Assessing Fundamental Mechanisms of Neuroma

> **NIH VA I21** · LOUISVILLE VA MEDICAL MEDICAL CENTER · 2024 · —

## Abstract

Neuromas are painful tumors of nerve tissue that result from amputation or other nerve injury. Peripheral nerve
injury is the most-impactful comorbidity associated with the most common types of battlefield trauma, and
many of these cases eventually result in formation of a painful neuroma. This condition often requires
additional invasive surgery for our Veterans, including resectioning of the injured nerve to remove the
neuroma, which may form again. Diabetes, a chronic health problem that is a priority for VAMCs across the
country, is another common cause of amputation. Neuroma pain (or “nerve pain” as it is commonly called in
the amputee community) is also one of the major reasons patients reduce/stop use of assistive devices,
including prosthetics. Further, presence of neuroma can be a disqualifying factor for some prosthetics and
nerve interfaces. Although treatments are available, there is currently no clinical Standard of Care for
prevention or treatment of neuroma because the available approaches are not sufficiently effective. Although
essentially all unrepaired nerve injuries result in a neuroma, not all neuromas are painful. Unfortunately, there
is no “safe window” for neuromas – pain can begin at any point after the nerve injury which induced the
neuroma. Neuromas continue to grow and their structure evolves over time, likely introducing interactions that
would not occur in normal tissue and developing emergent properties. These etiological factors suggest that,
although sensory neurons are necessary for neuroma pain, it is the neuroma structure itself that may establish
the physical relationships which lead to pain. Therefore, understanding what factors control formation of
neuroma structure is necessary to develop approaches to prevent neuroma formation.
 Our plan, to be pursued in subsequent MERIT applications, will tests the hypothesis that it is regeneration of
injured axons which controls neuroma formation, and that subsequent aberrant coupling of sympathetic or
motor axons and/or immune cells with sensory axons is the major factor driving neuroma pain. To this end, this
SPiRE proposal is designed to validate genetic models and experimental designs to enable us, and the field, to
address fundamental questions which remain unanswered. This project will test the utility of a set of cell type-
specific knockout and reporter mice for neuroma research. The premise for the proposed mouse lines is that
neuroma formation is apparently completely prevented by global knockout of a gene required for axonal
regeneration. The premise for the new experimental design is that no existing animal models reflect the clinical
reality of the repeated nerve injury that occurs with neuroma resection and recurrence, despite the fact that the
condition of repeated injury induces changes that differ from that of single injuries. This SPiRE project will
provide the animal lines, visualization methods, and preliminary data vital for MERIT projects to deter...

## Key facts

- **NIH application ID:** 10925141
- **Project number:** 5I21RX003766-03
- **Recipient organization:** LOUISVILLE VA MEDICAL MEDICAL CENTER
- **Principal Investigator:** Jeffrey C Petruska
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925141

## Citation

> US National Institutes of Health, RePORTER application 10925141, Developing Novel Models for Assessing Fundamental Mechanisms of Neuroma (5I21RX003766-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10925141. Licensed CC0.

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