Nerve-End Capping Treatment with a Polyglycolic Acid Conduit for Rat Sciatic Neuroma: A Preliminary Report

 

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Abstract

Background The treatment of painful neuroma remains challenging. Recently, a nerve-end capping technique using a bioabsorbable nerve conduit was newly introduced to treat amputation neuroma. A collagen-coated polyglycolic acid (PGA) conduit has been commercially available for the reconstruction of peripheral nerve defects, yielding successful clinical outcomes. However, no experimental research has been conducted using this PGA nerve conduit as capping device for treating amputation neuroma. The purpose of this study was to investigate nerve-end capping treatment with the PGA conduit in the rat sciatic nerve amputation model, focusing on histological scar formation and neuroinflammation.

Methods Forty-seven rats were divided into two groups: no capping (transected nerve stump without capping; n = 25) and capping (nerve-end capping with collagen-coated PGA nerve conduit; n = 22). Twelve weeks after sciatic neurectomy, neuropathic pain was evaluated using the autotomy score. Stump neuromas were histologically evaluated or perineural scar and neuroinflammation.

Results While autotomy scores gradually exacerbated in both groups, they were consistently lower in the capping group at 4, 8, and 12 weeks postprocedure. Twelve weeks after surgery, the transected nerve stumps in the no-capping group had formed macroscopic bulbous neuromas strongly adhering to surrounding tissues, whereas they remained wrapped with the PGA nerve conduits loosely adhering to surrounding tissues in the capping group. Histologically, distal axonal fibers were expanded radially and formed neuromas in the no-capping group, while they were terminated within the PGA conduit in the capping group. Perineural scars and neuroinflammation were widely found surrounding the randomly sprouting nerve end in the no-capping group. In capped counterparts, scars and inflammation were limited to closely around the terminated nerve end.

Conclusion Nerve-end capping with a collagen-coated PGA conduit after rat sciatic neurectomy might prevent neuroma formation by suppressing perineural scar formation and neuroinflammation around the nerve stump, potentially relieving neuropathic pain.

Publication History

Received: 26 May 2021

Accepted: 30 January 2022

Article published online:
19 September 2022

© 2022. Thieme. All rights reserved.

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• References

• 1 Yao C, Zhou X, Zhao B, Sun C, Poonit K, Yan H. Treatments of traumatic neuropathic pain: a systematic review. Oncotarget 2017; 8 (34) 57670-57679
  CrossrefPubMedGoogle Scholar
• 2 Toia F, Giesen T, Giovanoli P, Calcagni M. A systematic review of animal models for experimental neuroma. J Plast Reconstr Aesthet Surg 2015; 68 (10) 1447-1463
  CrossrefPubMedGoogle Scholar
• 3 van der Avoort DJ, Hovius SE, Selles RW, van Neck JW, Coert JH. The incidence of symptomatic neuroma in amputation and neurorrhaphy patients. J Plast Reconstr Aesthet Surg 2013; 66 (10) 1330-1334
  CrossrefPubMedGoogle Scholar
• 4 Elliot D. Surgical management of painful peripheral nerves. Clin Plast Surg 2014; 41 (03) 589-613
  CrossrefPubMedGoogle Scholar
• 5 Dellon AL, Mackinnon SE. Treatment of the painful neuroma by neuroma resection and muscle implantation. Plast Reconstr Surg 1986; 77 (03) 427-438
  CrossrefPubMedGoogle Scholar
• 6 Mass DP, Ciano MC, Tortosa R, Newmeyer WL, Kilgore Jr ES. Treatment of painful hand neuromas by their transfer into bone. Plast Reconstr Surg 1984; 74 (02) 182-185
  CrossrefPubMedGoogle Scholar
• 7 Kakinoki R, Ikeguchi R, Matsumoto T, Shimizu M, Nakamura T. Treatment of painful peripheral neuromas by vein implantation. Int Orthop 2003; 27 (01) 60-64
  CrossrefPubMedGoogle Scholar
• 8 Kakinoki R, Ikeguchi R, Atiyya AN, Nakamura T. Treatment of posttraumatic painful neuromas at the digit tip using neurovascular island flaps. J Hand Surg Am 2008; 33 (03) 348-352
  CrossrefPubMedGoogle Scholar
• 9 Wu J, Chiu DT. Painful neuromas: a review of treatment modalities. Ann Plast Surg 1999; 43 (06) 661-667
  CrossrefPubMedGoogle Scholar
• 10 Lans J, Hoftiezer Y, Lozano-Calderón SA, Heng M, Valerio IL, Eberlin KR. Risk factors for neuropathic pain following major upper extremity amputation. J Reconstr Microsurg 2021; 37 (05) 413-420
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am 2013; 95 (23) 2144-2151
  CrossrefPubMedGoogle Scholar
• 12 Gould JS, Naranje SM, McGwin Jr G, Florence M, Cheppalli S. Use of collagen conduits in management of painful neuromas of the foot and ankle. Foot Ankle Int 2013; 34 (07) 932-940
  CrossrefPubMedGoogle Scholar
• 13 Parker RG, Merced-O'Neil O. Management of painful recurrent intermetatarsal neuroma using processed porcine extracellular matrix material: a case report. Clin Podiatr Med Surg 2016; 33 (02) 235-242
  CrossrefPubMedGoogle Scholar
• 14 de Ru JA, M Thomeer HGX, Tijink BM, van Doormaal TPC. Neurocap use for the treatment of iatrogenic neuropathic pain: preliminary operative results in 3 patients. Ear Nose Throat J 2021; 100 (5_suppl1): 830S-834S
  CrossrefPubMedGoogle Scholar
• 15 Uemura T, Onode E, Yokoi T. et al. Nerve capping technique with nerve conduit for treating painful digital neuroma: a case report. J Orthop Sci 2022; 27 (01) 284-287
  CrossrefPubMedGoogle Scholar
• 16 Onode E, Uemura T, Takamatsu K. et al. Nerve capping with a nerve conduit for the treatment of painful neuroma in the rat sciatic nerve. J Neurosurg 2019; 132 (03) 856-864
  CrossrefPubMedGoogle Scholar
• 17 Yi J, Jiang N, Li B. et al. Painful terminal neuroma prevention by capping PRGD/PDLLA conduit in rat sciatic nerves. Adv Sci (Weinh) 2018; 5 (06) 1700876
  CrossrefPubMedGoogle Scholar
• 18 Weng W, Zhao B, Lin D, Gao W, Li Z, Yan H. Significance of alpha smooth muscle actin expression in traumatic painful neuromas: a pilot study in rats. Sci Rep 2016; 6: 23828
  CrossrefPubMedGoogle Scholar
• 19 Yan H, Zhang F, Wang C, Xia Z, Mo X, Fan C. The role of an aligned nanofiber conduit in the management of painful neuromas in rat sciatic nerves. Ann Plast Surg 2015; 74 (04) 454-461
  CrossrefPubMedGoogle Scholar
• 20 Yan H, Zhang F, Kolkin J, Wang C, Xia Z, Fan C. Mechanisms of nerve capping technique in prevention of painful neuroma formation. PLoS One 2014; 9 (04) e93973
  CrossrefPubMedGoogle Scholar
• 21 Yan H, Gao W, Pan Z, Zhang F, Fan C. The expression of α-SMA in the painful traumatic neuroma: potential role in the pathobiology of neuropathic pain. J Neurotrauma 2012; 29 (18) 2791-2797
  CrossrefPubMedGoogle Scholar
• 22 Okuda T, Ishida O, Fujimoto Y. et al. The autotomy relief effect of a silicone tube covering the proximal nerve stump. J Orthop Res 2006; 24 (07) 1427-1437
  CrossrefPubMedGoogle Scholar
• 23 Sakai Y, Ochi M, Uchio Y, Ryoke K, Yamamoto S. Prevention and treatment of amputation neuroma by an atelocollagen tube in rat sciatic nerves. J Biomed Mater Res B Appl Biomater 2005; 73 (02) 355-360
  CrossrefPubMedGoogle Scholar
• 24 Kusuhara H, Hirase Y, Isogai N, Sueyoshi Y. A clinical multi-center registry study on digital nerve repair using a biodegradable nerve conduit of PGA with external and internal collagen scaffolding. Microsurgery 2019; 39 (05) 395-399
  CrossrefPubMedGoogle Scholar
• 25 Zukawa M, Osada R, Kimura T. Clinical outcome and ultrasonographic evaluation of treatment using polyglycolic acid-collagen tube for chronic neuropathic pain after peripheral nerve injury. J Orthop Sci 2019; 24 (06) 1064-1067
  CrossrefPubMedGoogle Scholar
• 26 Suzuki H, Araki K, Matsui T. et al. Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model. Laryngoscope 2016; 126 (07) E233-E239
  CrossrefPubMedGoogle Scholar
• 27 Yamanaka T, Hosoi H, Murai T, Kobayashi T, Inada Y, Nakamura T. Regeneration of the nerves in the aerial cavity with an artificial nerve conduit –reconstruction of chorda tympani nerve gaps. PLoS One 2014; 9 (04) e92258
  CrossrefPubMedGoogle Scholar
• 28 Saltzman EB, Villa JC, Doty SB, Feinberg JH, Lee SK, Wolfe SW. A comparison between two collagen nerve conduits and nerve autograft: a rat model of motor nerve regeneration. J Hand Surg Am 2019; 44 (08) 700.e1-700.e9
  CrossrefPubMedGoogle Scholar
• 29 Wall PD, Devor M, Inbal R. et al. Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 1979; 7 (02) 103-113
  CrossrefPubMedGoogle Scholar
• 30 Shintani K, Uemura T, Takamatsu K. et al. Protective effect of biodegradable nerve conduit against peripheral nerve adhesion after neurolysis. J Neurosurg 2018; 129 (03) 815-824
  CrossrefPubMedGoogle Scholar
• 31 de Vrij EL, Schäfer TR, van Mulken T, Bertleff MJOE. Surgical treatment of symptomatic neuromas: a feasibility study using the NEUROCAP® bioresorbable nerve capping device. J Hand Surg Eur Vol 2022; 47 (02) 212-214
  CrossrefPubMedGoogle Scholar
• 32 George S, Pohl U, Power D. Analysis of an end neuroma 6 months after capping with a bioresorbable polycaprolactone cap (NEUROCAP®) in a human model. Surg Case Rep 2020; 3: 2-4
  PubMedGoogle Scholar
• 33 McNamara CT, Iorio ML. Targeted muscle reinnervation: outcomes in treating chronic pain secondary to extremity amputation and phantom limb syndrome. J Reconstr Microsurg 2020; 36 (04) 235-240
  Article in Thieme ConnectPubMedGoogle Scholar
• 34 Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted muscle reinnervation: a novel approach to postamputation neuroma pain. Clin Orthop Relat Res 2014; 472 (10) 2984-2990
  CrossrefPubMedGoogle Scholar
• 35 Swanson AB, Boeve NR, Lumsden RM. The prevention and treatment of amputation neuromata by silicone capping. J Hand Surg Am 1977; 2 (01) 70-78
  CrossrefPubMedGoogle Scholar
• 36 Shen B, Behera D, James ML. et al. Visualizing nerve injury in a neuropathic pain model with [¹⁸F]FTC-146 PET/MRI. Theranostics 2017; 7 (11) 2794-2805
  CrossrefPubMedGoogle Scholar
• 37 Romero L, Zamanillo D, Nadal X. et al. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization. Br J Pharmacol 2012; 166 (08) 2289-2306
  CrossrefPubMedGoogle Scholar
• 38 Puente B, Nadal X, Portillo-Salido E. et al. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain 2009; 145 (03) 294-303
  CrossrefPubMedGoogle Scholar
• 39 Nieto FR, Cendán CM, Cañizares FJ. et al. Genetic inactivation and pharmacological blockade of sigma-1 receptors prevent paclitaxel-induced sensory-nerve mitochondrial abnormalities and neuropathic pain in mice. Mol Pain 2014; 10: 11
  CrossrefPubMedGoogle Scholar
• 40 Petersen J, Russell L, Andrus K, MacKinnon M, Silver J, Kliot M. Reduction of extraneural scarring by ADCON-T/N after surgical intervention. Neurosurgery 1996; 38 (05) 976-983 , discussion 983–984
  CrossrefPubMedGoogle Scholar
• 41 Crosio A, Valdatta L, Cherubino M. et al. A simple and reliable method to perform biomechanical evaluation of postoperative nerve adhesions. J Neurosci Methods 2014; 233: 73-77
  CrossrefPubMedGoogle Scholar
• 42 Shin RH, Friedrich PF, Crum BA, Bishop AT, Shin AY. Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. J Bone Joint Surg Am 2009; 91 (09) 2194-2204
  CrossrefPubMedGoogle Scholar