J Reconstr Microsurg 2021; 37(05): 413-420
DOI: 10.1055/s-0040-1718547
Original Article

Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation

Jonathan Lans
1   Department of Orthopaedic Surgery, Hand and Upper Extremity Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Yannick Hoftiezer
1   Department of Orthopaedic Surgery, Hand and Upper Extremity Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Santiago A. Lozano-Calderón
2   Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Marilyn Heng
3   Department of Orthopedic Surgery, Harvard Medical School Orthopedic Trauma Initiative, Massachusetts General Hospital, Boston, Massachusetts
,
Ian L. Valerio
4   Division of Plastic Surgery, Hand Surgery, and Peripheral Nerve Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
,
Kyle R. Eberlin
4   Division of Plastic Surgery, Hand Surgery, and Peripheral Nerve Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
› Institutsangaben

Abstract

Background Active treatment (targeted muscle reinnervation [TMR] or regenerative peripheral nerve interfaces [RPNIs]) of the amputated nerve ends has gained momentum to mitigate neuropathic pain following amputation. Therefore, the aim of this study is to determine the predictors for the development of neuropathic pain after major upper extremity amputation.

Methods Retrospectively, 142 adult patients who underwent 148 amputations of the upper extremity between 2000 and 2019 were identified through medical chart review. All upper extremity amputations proximal to the metacarpophalangeal joints were included. Patients with a follow-up of less than 6 months and those who underwent TMR or RPNI at the time of amputation were excluded. Neuropathic pain was defined as phantom limb pain or a symptomatic neuroma reported in the medical charts at 6 months postoperatively. Most common indications for amputation were oncology (n = 53, 37%) and trauma (n = 45, 32%), with transhumeral amputations (n = 44, 30%) and shoulder amputations (n = 37, 25%) being the most prevalent.

Results Neuropathic pain occurred in 42% of patients, of which 48 (32%) had phantom limb pain, 8 (5.4%) had a symptomatic neuroma, and 6 (4.1%) had a combination of both. In multivariable analysis, traumatic amputations (odds ratio [OR]: 4.1, p = 0.015), transhumeral amputations (OR: 3.9, p = 0.024), and forequarter amputations (OR: 8.4, p = 0.003) were independently associated with the development of neuropathic pain.

Conclusion In patients with an upper extremity amputation proximal to the elbow or for trauma, there is an increased risk of developing neuropathic pain. In these patients, primary TMR/RPNI should be considered and this warrants a multidisciplinary approach involving general trauma surgeons, orthopaedic surgeons, plastic surgeons, and vascular surgeons.

Authors' Contribution

Study design: J.L., S.A.L.C., M.H., I.L.V., and K.R.E; data assembly: J.L. and Y.H.; data analysis: J.L. and Y.H.; initial draft: J.L., Y.H., S.A.L.C., M.H., I.L.V., and K.R.E; final approval of manuscript: J.L., Y.H., S.L.C., M.H., I.L.V., and K.R.E.


Supplementary Material



Publikationsverlauf

Eingereicht: 17. Mai 2020

Angenommen: 02. September 2020

Artikel online veröffentlicht:
14. Oktober 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Inkellis E, Low EE, Langhammer C, Morshed S. Incidence and characterization of major upper-extremity amputations in the National Trauma Data Bank. JBJS Open Access 2018; 3 (02) e0038
  • 2 Nawijn F, Westenberg RF, Langhammer CG, Chen NC, Eberlin KR. Factors associated with primary and secondary amputation following limb-threatening upper extremity trauma. Plast Reconstr Surg 2020; 145 (04) 987-999
  • 3 Geraghty TJ, Jones LE. Painful neuromata following upper limb amputation. Prosthet Orthot Int 1996; 20 (03) 176-181
  • 4 Resnik L, Ekerholm S, Borgia M, Clark MA. A national study of veterans with major upper limb amputation: survey methods, participants, and summary findings. PLoS One 2019; 14 (03) e0213578
  • 5 Kooijman CM, Dijkstra PU, Geertzen JH, Elzinga A, van der Schans CP. Phantom pain and phantom sensations in upper limb amputees: an epidemiological study. Pain 2000; 87 (01) 33-41
  • 6 Dijkstra PU, Geertzen JHB, Stewart R, van der Schans CP. Phantom pain and risk factors: a multivariate analysis. J Pain Symptom Manage 2002; 24 (06) 578-585
  • 7 Singh RK, Prasad G. Long-term mortality after lower-limb amputation. Prosthet Orthot Int 2016; 40 (05) 545-551
  • 8 Morgan SJ, Friedly JL, Amtmann D, Salem R, Hafner BJ. Cross-sectional assessment of factors related to pain intensity and pain interference in lower limb prosthesis users. Arch Phys Med Rehabil 2017; 98 (01) 105-113
  • 9 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
  • 10 Eberlin KR, Ducic I. Surgical algorithm for neuroma management: a changing treatment paradigm. Plast Reconstr Surg Glob Open 2018; 6 (10) e1952
  • 11 Lans J, Baker DJ, Castelein RM, Sood RF, Chen NC, Eberlin KR. Patient-reported outcomes following surgical treatment of symptomatic digital neuromas. Plast Reconstr Surg 2020; 145 (03) 563e-573e
  • 12 Guse DM, Moran SL. Outcomes of the surgical treatment of peripheral neuromas of the hand and forearm: a 25-year comparative outcome study. Ann Plast Surg 2013; 71 (06) 654-658
  • 13 Wolvetang NHA, Lans J, Verhiel SHWL, Notermans BJW, Chen NC, Eberlin KR. Surgery for symptomatic neuroma: anatomic distribution and predictors of secondary surgery. Plast Reconstr Surg 2019; 143 (06) 1762-1771
  • 14 Ives GC, Kung TA, Nghiem BT. et al. Current state of the surgical treatment of terminal neuromas. Neurosurgery 2018; 83 (03) 354-364
  • 15 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
  • 16 Dumanian GA, Potter BK, Mioton LM. et al. Targeted muscle reinnervation treats neuroma and phantom pain in major limb amputees: a randomized clinical trial. Ann Surg 2019; 270 (02) 238-246
  • 17 Woo SL, Kung TA, Brown DL, Leonard JA, Kelly BM, Cederna PS. Regenerative peripheral nerve interfaces for the treatment of postamputation neuroma pain: a pilot study. Plast Reconstr Surg Glob Open 2016; 4 (12) e1038
  • 18 Zip Code Characteristics: Mean and Median Household Income, Michigan Population Studies Center. Available at: https://www.psc.isr.umich.edu/dis/census/Features/tract2zip/. Accessed September 23, 2020
  • 19 van Walraven C, Austin PC, Jennings A, Quan H, Forster AJ. A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care 2009; 47 (06) 626-633
  • 20 Quan H, Sundararajan V, Halfon P. et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43 (11) 1130-1139
  • 21 Ephraim PL, Wegener ST, MacKenzie EJ, Dillingham TR, Pezzin LE. Phantom pain, residual limb pain, and back pain in amputees: results of a national survey. Arch Phys Med Rehabil 2005; 86 (10) 1910-1919
  • 22 Weiss SA, Lindell B. Phantom limb pain and etiology of amputation in unilateral lower extremity amputees. J Pain Symptom Manage 1996; 11 (01) 3-17
  • 23 Raichle KA, Hanley MA, Molton I. et al. Prosthesis use in persons with lower- and upper-limb amputation. J Rehabil Res Dev 2008; 45 (07) 961-972
  • 24 Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil 2008; 89 (03) 422-429
  • 25 Gustafsson M, Amilon A, Ahlström G. Trauma-related distress and mood disorders in the early stage of an acute traumatic hand injury. J Hand Surg Br 2003; 28 (04) 332-338
  • 26 Desmond D, Gallagher P, Henderson-Slater D, Chatfield R. Pain and psychosocial adjustment to lower limb amputation amongst prosthesis users. Prosthet Orthot Int 2008; 32 (02) 244-252
  • 27 Domeshek LF, Krauss EM, Snyder-Warwick AK. et al. Surgical treatment of neuromas improves patient-reported pain, depression, and quality of life. Plast Reconstr Surg 2017; 139 (02) 407-418
  • 28 Bosmans JC, Geertzen JHB, Post WJ, Van Der Schans CP, Dijkstra PU. Factors associated with phantom limb pain: a 3 1/2-year prospective study. Clin Rehabil 2010; 24 (05) 444-453
  • 29 Kim J, Lonner JH, Nelson CL, Lotke PA. Response bias: effect on outcomes evaluation by mail surveys after total knee arthroplasty. J Bone Joint Surg Am 2004; 86 (01) 15-21
  • 30 Geraghty T, Jones L. Painful neuromata following upper limb amputation. Prosthet Orthot Int 1996; 20 (03) 176-181
  • 31 Oliveira KMC, Pindur L, Han Z, Bhavsar MB, Barker JH, Leppik L. Time course of traumatic neuroma development. PLoS One 2018; 13 (07) e0200548
  • 32 Mackinnon SE, Dellon AL, Hudson AR, Hunter DA. Alteration of neuroma formation by manipulation of its microenvironment. Plast Reconstr Surg 1985; 76 (03) 345-353
  • 33 Davies AJ, Rinaldi S, Costigan M, Oh SB. Cytotoxic immunity in peripheral nerve injury and pain. Front Neurosci 2020; 14 (February): 142
  • 34 Tanga FY, Raghavendra V, Nutile-McMenemy N, Marks A, Deleo JA. Role of astrocytic S100β in behavioral hypersensitivity in rodent models of neuropathic pain. Neuroscience 2006; 140 (03) 1003-1010
  • 35 Anand P. Nerve growth factor regulates nociception in human health and disease. Br J Anaesth 1995; 75 (02) 201-208
  • 36 Finnerup NB, Nikolajsen L, Jensen TS. Are we neglecting spinal reorganization following nerve damage?. Pain 2012; 153 (02) 269-272
  • 37 Davis KD, Kiss ZH, Luo L, Tasker RR, Lozano AM, Dostrovsky JO. Phantom sensations generated by thalamic microstimulation. Nature 1998; 391 (6665): 385-387
  • 38 Karl A, Birbaumer N, Lutzenberger W, Cohen LG, Flor H. Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain. J Neurosci 2001; 21 (10) 3609-3618
  • 39 Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152 (03) S2-S15
  • 40 Ortiz R, Westenberg RF, Langhammer CG, Knaus WJ, Chen NC, Eberlin KR. Nerve diameter in the hand: a cadaveric study. Plast Reconstr Surg Glob Open 2019; 7 (03) e2155
  • 41 Vlot MA, Wilkens SC, Chen NC, Eberlin KR. Symptomatic neuroma following initial amputation for traumatic digital amputation. J Hand Surg Am 2018; 43 (01) 86.e1-86.e8
  • 42 Lord JM, Midwinter MJ, Chen YF. et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet 2014; 384 (9952): 1455-1465
  • 43 Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: actions and mechanisms of action. Trends Neurosci 1995; 18 (03) 130-136
  • 44 Grace PM, Strand KA, Galer EL, Rice KC, Maier SF, Watkins LR. Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats. Brain Behav Immun 2018; 72: 45-50
  • 45 Kuiken TA, Li G, Lock BA. et al. Targeted muscle reinnervation for real-time myoelectric control of multifunction artificial arms. JAMA 2009; 301 (06) 619-628
  • 46 Langhals NB, Woo SL, Moon JD. et al. Electrically stimulated signals from a long-term regenerative peripheral nerve interface. Conf Proc IEEE Eng Med Biol Soc 2014; 2014: 1989-1992
  • 47 Dumanian GA, Ko JH, O'Shaughnessy KD, Kim PS, Wilson CJ, Kuiken TA. Targeted reinnervation for transhumeral amputees: current surgical technique and update on results. Plast Reconstr Surg 2009; 124 (03) 863-869
  • 48 Valerio I, Schulz SA, West J, Westenberg RF, Eberlin KR. Targeted muscle reinnervation combined with a vascularized pedicled regenerative peripheral nerve interface. Plast Reconstr Surg Glob Open 2020; 8 (03) e2689
  • 49 Woo SL, Urbanchek MG, Cederna PS, Langhals NB. Revisiting nonvascularized partial muscle grafts: a novel use for prosthetic control. Plast Reconstr Surg 2014; 134 (02) 344e-346e
  • 50 Kim PS, Ko JH, O'Shaughnessy KK, Kuiken TA, Pohlmeyer EA, Dumanian GA. The effects of targeted muscle reinnervation on neuromas in a rabbit rectus abdominis flap model. J Hand Surg Am 2012; 37 (08) 1609-1616
  • 51 Serino A, Akselrod M, Salomon R. et al. Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation. Brain 2017; 140 (11) 2993-3011
  • 52 Birbaumer N, Lutzenberger W, Montoya P. et al. Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization. J Neurosci 1997; 17 (14) 5503-5508
  • 53 Valerio IL, Dumanian GA, Jordan SW. et al. Preemptive treatment of phantom and residual limb pain with targeted muscle reinnervation at the time of major limb amputation. J Am Coll Surg 2019; 228 (03) 217-226
  • 54 Alexander JH, Jordan SW, West JM. et al. Targeted muscle reinnervation in oncologic amputees: early experience of a novel institutional protocol. J Surg Oncol 2019; 120 (03) 348-358
  • 55 Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic regenerative peripheral nerve interfaces to prevent postamputation pain. Plast Reconstr Surg 2019; 144 (03) 421e-430e