title: The role of different methods of nerve ablation in prevention of neuroma.
abstract: BACKGROUND
  The aim of this study was to compare the incidence of neuroma formation and neuropathic pain following different techniques of nerve ablation in a rat sural nerve model.
  
  
  METHODS
  Rat sural nerve was subjected to four different techniques of ablation with standardized creation of a 1-cm gap (n = 15 in each group). These included nerve avulsion, transection and burying in muscle, transection and folding of nerve, and transection alone. Animals were killed after 3 months. Explanted nerves were sectioned and stained with Masson trichrome and S-100 stain against neural tissue. The maximal neural cross-sectional area and neural-to-connective tissue ratio was quantified. Quantitative reverse-transcriptase polymerase chain reaction (n = 5) was used to analyze relative mRNA expression of ciliary neurotrophic factor and calcitonin gene-related peptide.
  
  
  RESULTS
  Neural cross-sectional area was statistically increased (p < 0.05) compared with controls in folded, muscle buried, and transected specimens but decreased in avulsed specimens. The neural-to-connective tissue ratio was statistically decreased in the avulsed group. Relative mRNA expression of ciliary neurotrophic factor was lowest in muscle buried (4 percent of control) (p < 0.05) and avulsed specimens (15 percent of control) (p < 0.05) and higher in folded (52 percent of control) and transected specimens (75 percent of control). Relative mRNA expression of calcitonin gene-related peptide was highest in folded specimens (302 percent of control) (p < 0.05).
  
  
  CONCLUSIONS
  Folding and transection lead to increased histologic evidence of neuroma formation, whereas folding leads to neuropathic pain, assayed by calcitonin gene-related peptide expression. Avulsion and muscle burying are preferable techniques for nerve ablation and inhibit nerve regeneration, evidenced by decreased ciliary neurotrophic factor expression. Avulsion offers an alternative to muscle burying when there is no muscle in the vicinity to bury the transected nerve.
authors: Cleveland, Ohio From the Department of Plastic Surgery and the Department of Pathology, Case Western Reserve University.
authors: Harvey
authors: H
authors: Chim
authors: Erin
authors: E
authors: Miller
authors: Christy
authors: C
authors: Gliniak
authors: Mark L
authors: ML
authors: Cohen
authors: Bahman
authors: B
authors: Guyuron
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D004195:Disease Models, Animal; D018482:Muscle, Skeletal / Q000294:innervation / Q000601:surgery; D009437:Neuralgia / Q000473:pathology / Q000517:prevention & control; D009463:Neuroma / Q000473:pathology / Q000517:prevention & control*; D019635:Neurosurgical Procedures / Q000379:methods*; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000601:surgery*; D010524:Peripheral Nervous System Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013497:Sural Nerve / Q000601:surgery*
chemical_list: D020934:Ciliary Neurotrophic Factor; D012333:RNA, Messenger; D015740:Calcitonin Gene-Related Peptide
references: Janes S, Renaut PH, Gordon MK. Traumatic (or amputation) neuroma. ANZ J Surg. 2004;74:701–702
references: Zimmerman M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429:23–37
references: Dellon AL, Mackinnon SE. Treatment of the painful neuroma by neuroma resection and muscle implantation. Plast Reconstr Surg. 1986;77:427–438
references: Otfinowski J, Pawelec A, Kałuza J. Implantation of peripheral neural stump into muscle and its effect on the development of posttraumatic neuroma. Pol J Pathol. 1994;45:195–202
references: Herbert TJ, Filan SL. Vein implantation for treatment of painful cutaneous neuromas: A preliminary report. J Hand Surg Br. 1998;23:220–224
references: Marcol W, Kotulska K, Larysz-Brysz M, et al. Prevention of painful neuromas by oblique transection of peripheral nerves. J Neurosurg. 2006;104:285–289
references: Guyuron B, Reed D, Kriegler JS, Davis J, Pashmini N, Amini S. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg. 2009;124:461–468
references: Dubový P, Raška O, Klusáková I, Stejskal L, Celakovský P, Haninec P. Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy. BMC Neurosci. 2011;12:58
references: Leibinger M, Müller A, Andreadaki A, Hauk TG, Kirsch M, Fischer D. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci. 2009;29:14334–14341
references: Jaggi AS, Singh N. Therapeutic targets for the management of peripheral nerve injury-induced neuropathic pain. CNS Neurol Disord Drug Targets. 2011;10:589–609
references: Michot B, Bourgoin S, Viguier F, Hamon M, Kayser V. Differential effects of calcitonin gene-related peptide receptor blockade by olcegepant on mechanical allodynia induced by ligation of the infraorbital nerve vs the sciatic nerve in the rat. Pain. 2012;153:1939–1948
references: Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45
references: Ducic I, Mafi AA, Attinger CE, Couch K, Al-Attar A. The role of peripheral nerve surgery in the management of painful chronic wounds: Indications and outcomes. Plast Reconstr Surg. 2008;122:193–197
references: Ducic I, Larson EE. Posttraumatic headache: Surgical management of supraorbital neuralgia. Plast Reconstr Surg. 2008;121:1943–1948
references: Guyuron B, Kriegler JS, Davis J, Amini SB. Comprehensive surgical treatment of migraine headaches. Plast Reconstr Surg. 2005;115:1–9
references: Guyuron B, Kriegler JS, Davis J, Amini SB. Five-year outcome of surgical treatment of migraine headaches. Plast Reconstr Surg. 2011;127:603–608
references: Mackinnon SE, Dellon AL, Hudson AR, Hunter DA. Alteration of neuroma formation by manipulation of its microenvironment. Plast Reconstr Surg. 1985;76:345–353
references: Dellon AL, Mackinnon SE. Treatment of the painful neuroma by neuroma resection and muscle implantation. Plast Reconstr Surg. 1986;77:427–438
references: Yildirim AM, Okur MI, Ozveren F, Ozercan R. Reduction of the incidence of neuroma formation by proximal epineural stripping: An experimental study in rats. J Hand Surg Br. 2006;31:450–452
references: Sinis N, Haerle M, Becker ST, et al. Neuroma formation in a rat median nerve model: Influence of distal stump and muscular coating. Plast Reconstr Surg. 2007;119:960–966
references: Janis JE, Hatef DA, Thakar H, et al. The zygomaticotemporal branch of the trigeminal nerve: Part II. Anatomical variations. Plast Reconstr Surg. 2010;126:435–442
references: Ip NY, Yancopoulos GD. The neurotrophins and CNTF: Two families of collaborative neurotrophic factors. Annu Rev Neurosci. 1996;19:491–515
references: Rabinovsky ED, Smith GM, Browder DP, et al. Peripheral nerve injury down-regulates CNTF expression in adult rat sciatic nerves. J Neurosci Res. 1992;31:188–192
references: Smith GM, Rabinovsky ED, McManaman JL, et al. Temporal and spatial expression of ciliary neurotrophic factor after peripheral nerve injury. Exp Neurol. 1993;121:239–247
references: Zachary LS, Dellon AL, Seiler WA IV. Relationship of intraneural damage in the rat sciatic nerve to the mechanism of injury. J Reconstr Microsurg. 1989;5:137–140
references: Zhang YQ, Guo N, Peng G, et al. Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain. Pain. 2009;146:130–140
references: Cridland RA, Henry JL. Intrathecal administration of CGRP in the rat attenuates a facilitation of the tail flick reflex induced by either substance P or noxious cutaneous stimulation. Neurosci Lett. 1989;102:241–246
references: Bennett AD, Chastain KM, Hulsebosch CE. Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain. Pain. 2000;86:163–175
references: Grelik C, Bennett GJ, Ribeiro-da-Silva A. Autonomic fibre sprouting and changes in nociceptive sensory innervation in the rat lower lip skin following chronic constriction injury. Eur J Neurosci. 2005;21:2475–2487
references: Ma W, Quirion R. Increased calcitonin gene-related peptide in neuroma and invading macrophages is involved in the up-regulation of interleukin-6 and thermal hyperalgesia in a rat model of mononeuropathy. J Neurochem. 2006;98:180–192
references: McCoy ES, Taylor-Blake B, Zylka MJ. CGRPα-expressing sensory neurons respond to stimuli that evoke sensations of pain and itch. PLoS One. 2012;7:e36355