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J Brachial Plex Peripher Nerve Inj 2010; 05(01): e21-e28
DOI: 10.1186/1749-7221-5-6
Research article
Kim et al; licensee BioMed Central Ltd.

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

Peter S Kim
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
,
Jason Ko
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
,
Kristina K O’Shaughnessy
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
,
Todd A Kuiken
2   Neural Engineering Center for Artificial Limbs (NECAL), Rehabilitation Institute of Chicago, Chicago, IL, USA
,
Gregory A Dumanian
1   Department of Surgery, Division of Plastic and Reconstructive Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
› Author Affiliations
Subject Editor:
Further Information

Publication History

19 November 2009

18 March 2010

Publication Date:
19 September 2014 (online)

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Abstract

Background The 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.

Methods Upon 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.

Results The 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.

Conclusion Given 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.

*This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


 

  • References

  • 1 Ebrahimzadeh MH, Fattahi AS, Nejad AB. Long-term follow-up of Iranian veteran upper extremity amputees from the Iran-Iraq war (1980-1988). J Trauma 2006; 61 (4) 886-8 10.1097/01.ta.0000236014.78230.77 17033556
    CrossrefPubMedGoogle Scholar
  • 2 Munro D, Mallory GK. Elimination of the so-called amputation neuromas of divided peripheral nerves. N Engl J Med 1959; 260 (8) 358-61 13632892
    CrossrefPubMedGoogle Scholar
  • 3 Ducic I, Moriarity M, Al-Attar A. The role of peripheral nerve surgery in the treatment of chronic pain associated with amputation stumps. Plast Reconstr Surg 2008; 121 (3) 908-14 discussion 915-7 10.1097/01.prs.0000299281.57480.77 18317139
    CrossrefPubMedGoogle Scholar
  • 4 Dellon AL, Mackinnon SE. Treatment of the painful neuroma by neuroma resection and muscle implantation. Plast Reconstr Surg 1986; 77 (3) 427-38 10.1097/00006534-198603000-00016 2937074
    CrossrefPubMedGoogle Scholar
  • 5 Fried K, Govrin-Lippmann R, Rosenthal F, Devor M. Ultrastructure of afferent axon endings in a neuroma. J Neurocytol 1991; 20 (8) 682-701 10.1007/BF01187069 1719140
    CrossrefPubMedGoogle Scholar
  • 6 Fried K, Govrin-Lippmann R, Devor M. Close apposition among neighbouring axonal endings in a neuroma. J Neurocytol 1993; 22 (8) 663-81 10.1007/BF01181491 8229091
    CrossrefPubMedGoogle Scholar
  • 7 Aitken JT. The effect of peripheral connexions on the maturation of regenerating nerve fibres. J Anat 1949; 83 (Pt 1) 32-43
    PubMedGoogle Scholar
  • 8 Alsancak S, Erdemli B, Korkusuz Z. Effect on knee disarticulation on bone growth of immature rabbits. Prosthet Orthot Int 1997; 21 (3) 189-94 9453092
    PubMedGoogle Scholar
  • 9 Frogameni AD, Booth R, Mumaw LA, Cummings V. Comparison of soft dressing and rigid dressing in the healing of amputated limbs of rabbits. Am J Phys Med Rehabil 1989; 68 (5) 234-9 10.1097/00002060-198910000-00007 2803683
    CrossrefPubMedGoogle Scholar
  • 10 Hunter DA, Moradzadeh A, Whitlock EL, Brenner MJ, Myckatyn TM, Wei CH, Tung TH, Mackinnon SE. Binary imaging analysis for comprehensive quantitative histomorphometry of peripheral nerve. J Neurosci Methods 2007; 166 (1) 116-24 10.1016/j.jneumeth.2007.06.018 2587177 17675163
    CrossrefPubMedGoogle Scholar
  • 11 da Silva AP, Jordao CE, Fazan VP. Peripheral nerve morphometry: Comparison between manual and semi-automated methods in the analysis of a small nerve. J Neurosci Methods 2007; 159 (1) 153-7 10.1016/j.jneumeth.2006.06.012 16887196
    CrossrefPubMedGoogle Scholar
  • 12 Waller A. Experiments on the sections of glossopharyngeal and hypoglossal nerves of the frog and observations of the alterations produced thereby in the structures of their primitive fibers. Phil Trans R Soc Lond 1850 (140) 423-429
    PubMedGoogle Scholar
  • 13 Zhang F, Fischer KA. End-to-side neurorrhaphy. Microsurgery 2002; 22 (3) 122-7 10.1002/micr.21736 11992500
    CrossrefPubMedGoogle Scholar
  • 14 Slack JR, Hopkins WG, Williams MN. Nerve sheaths and motoneurone collateral sprouting. Nature 1979; 282 (5738) 506-7 10.1038/282506a0 503228
    CrossrefPubMedGoogle Scholar
  • 15 Torigoe K, Tanaka HG, Takahashi A, Hashimoto K. Early growth of regenerating neurites in acrylamide neuropathic mice: application of a film model. Brain Res 1997; 746 (1-2) 269-74 10.1016/S0006-8993(96)01260-7 9037506
    CrossrefPubMedGoogle Scholar
  • 16 Maggi SP, Lowe JB, Mackinnon SE. Pathophysiology of nerve injury. Clin Plast Surg 2003; 30 (2) 109-26 10.1016/S0094-1298(02)00101-3 12737347
    CrossrefPubMedGoogle Scholar
  • 17 Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 1997; 14 (1-2) 67-116 10.1007/BF02740621 9170101
    CrossrefPubMedGoogle Scholar
  • 18 Kuno M. Target dependence of motoneuronal survival: the current status. Neurosci Res 1990; 9 (3) 155-72 10.1016/0168-0102(90)90001-U 1963675
    CrossrefPubMedGoogle Scholar
  • 19 Sunderland S. Nerve and nerve injuries. Churchill Livingstone 1972;
    PubMedGoogle Scholar
  • 20 Song C, Zhang F, Zhang J, Mustain WC, Chen MB, Chen T, Lineaweaver WC. Neuroma-in-continuity model in rabbits. Ann Plast Surg 2006; 57 (3) 317-22 10.1097/01.sap.0000221512.06129.d3 16929202
    CrossrefPubMedGoogle Scholar
  • 21 Cravioto H, Battista A. Clinical and ultrastructural study of painful neuroma. Neurosurgery 1981; 8 (2) 181-90 10.1097/00006123-198102000-00007 7207783
    CrossrefPubMedGoogle Scholar
  • 22 Morris JH, Hudson AR, Weddell G. A study of degeneration and regeneration in the divided rat sciatic nerve based on electron microscopy. II. The development of the “regenerating unit”. Z Zellforsch Mikrosk Anat 1972; 124 (1) 103-30 10.1007/BF00981944 5011137
    CrossrefPubMedGoogle Scholar
  • 23 Tyner TR, Parks N, Faria S, Simons M, Stapp B, Curtis B, Sian K, Yamaguchi KT. Effects of collagen nerve guide on neuroma formation and neuropathic pain in a rat model. Am J Surg 2007; 193 (1) e1-6 10.1016/j.amjsurg.2006.08.026 17188077
    CrossrefPubMedGoogle Scholar
  • 24 Lago N, Navarro X. Evaluation of the long-term regenerative potential in an experimental nerve amputee model. J Peripher Nerv Syst 2007; 12 (2) 108-20 10.1111/j.1529-8027.2007.00130.x 17565536
    CrossrefPubMedGoogle Scholar
  • 25 Aszmann OC, Korak KJ, Rab M, Grunbeck M, Lassmann H, Frey M. Neuroma prevention by end-to-side neurorraphy: an experimental study in rats. J Hand Surg [Am] 2003; 28 (6) 1022-8 10.1016/S0363-5023(03)00379-4 14642521
    CrossrefPubMedGoogle Scholar
  • 26 Okuda T, Ishida O, Fujimoto Y, Tanaka N, Inoue A, Nakata Y, Ochi M. The autotomy relief effect of a silicone tube covering the proximal nerve stump. J Orthop Res 2006; 24 (7) 1427-37 10.1002/jor.20196 16732614
    CrossrefPubMedGoogle Scholar
  • 27 Sinis N, Haerle M, Becker ST, Schulte-Eversum C, Vonthein R, Rosner H, Schaller HE. Neuroma formation in a rat median nerve model: influence of distal stump and muscular coating. Plast Reconstr Surg 2007; 119 (3) 960-6 10.1097/01.prs.0000242486.70919.82 17312502
    CrossrefPubMedGoogle Scholar
  • 28 Dorsi M, Chen JL, Murinson BB, Pogatzki-Zahn EM, Meyer RA, Belzberg AJ. The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia. Pain 2008; 134 (3) 320-34 10.1016/j.pain.2007.06.030 17720318
    CrossrefPubMedGoogle Scholar