Novel model for end-neuroma formation in the amputated rabbit forelimb

Gregory Dumanian,Peter Kim,Todd Kuiken,Kristina O’Shaughnessy,Jason Ko

doi:10.1186/1749-7221-5-6

Abstract

BackgroundThe forelimb amputee poses many reconstructive challenges in the clinical setting, and there is a paucity of established surgical models for study. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model.MethodsUpon approval from the Institutional Animal Care and Use Committee, 5 New Zealand White rabbits underwent left forelimb amputation. During this initial surgery, the median, radial and ulnar nerves were transected 1.6-2.5 (mean 2.0) cm distal to the brachial plexus, transposed onto the anterior chest wall and preserved at length. Six weeks subsequent to the amputation, the distal 5 mm of each neuroma was excised, and the remaining stump underwent histomorphometric analysis.ResultsThe nerve cross sectional areas increased by factors of 1.99, 3.17, and 2.59 in the median (p = 0.077), radial (p < 0.0001) and the ulnar (p = 0.0026) nerves, respectively. At the axonal level, the number and cross-sectional area of myelinated fibers demonstrated an inverse relationship whereby the number of myelinated fibers in the median, radial and ulnar nerves increased by factors of 5.13 (p = 0.0043), 5.25 (p = 0.0056) and 5.59 (p = 0.0027), and the cross-sectional areas of these myelinated fibers decreased by factors of 4.62 (p < 0.001), 3.51 (p < 0.01), and 4.29 (p = 0.0259), respectively.ConclusionGiven that the surgical model appears well-tolerated by the rabbits and that patterns of morphologic change are consistent and reproducible, we are encouraged to further investigate the utility of this model in the pathogenesis of neuroma formation.

Highlights

In the modern era of military combat, there is an increasing incidence of extremity amputations [1], and though advances in body armor and trauma resuscitation have allowed soldiers to survive previously mortal wounds, the cost of survival is often a mangled or amputated extremity
Two key histologic characteristics of the end-neuroma are the sprouting of nerve fibers in the regenerating growth cone and a preponderance of dense collagen and fibroblastic stroma [5,6,7]; quantifying the
The advantages of this model include the following: 1) amputation of the forelimb and transection of the median, radial and ulnar nerves creates an environment that approximates the milieu seen in the human proximal upper extremity amputation; 2) a surgical technique that minimizes animal morbidity; and 3) the creation of an end-neuroma with quantifiable and reproducible histomorphometric parameters

Summary

Introduction

In the modern era of military combat, there is an increasing incidence of extremity amputations [1], and though advances in body armor and trauma resuscitation have allowed soldiers to survive previously mortal wounds, the cost of survival is often a mangled or amputated extremity. Neuroma formation from amputated nerve stumps can create a challenging clinical scenario since successful treatment of painful neuromas is often elusive [2,3,4], due in part to the activity of the regenerating nerve fibers at the amputation site. We describe a novel end-neuroma model in the amputated rabbit forelimb which has not been previously described in the literature The advantages of this model include the following: 1) amputation of the forelimb and transection of the median, radial and ulnar nerves creates an environment that approximates the milieu seen in the human proximal upper extremity amputation; 2) a surgical technique that minimizes animal morbidity; and 3) the creation of an end-neuroma with quantifiable and reproducible histomorphometric parameters. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model

Methods

Results

Conclusion