Early Postoperative Pain Course following Primary and Secondary Targeted Muscle Reinnervation: A Temporal Description of Pain Outcomes

Abstract

Background Targeted muscle reinnervation (TMR) is an effective surgical treatment of neuropathic pain for amputees. However, limited data exist regarding the early postoperative pain course for patients who undergo either primary (<14 days since amputation) or secondary (≥14 days) TMR. This study aims to outline the postoperative pain course for primary and secondary TMR during the first 6 postoperative months to aid in patient education and expectation management.

Methods Patients were eligible if they underwent TMR surgery between 2017 and 2023. Prospectively collected patient-reported outcome measures of pain scores, Pain Interference, and Pain Intensity were analyzed. Multilevel mixed-effects models were utilized to visualize and compare pain courses between primary and secondary TMR patients.

Results A total of 203 amputees were included, with 40.9% being primary and 59.1% being secondary TMR patients. Primary TMR patients reported significantly lower pain scores over the full 6-month postoperative trajectory (p < 0.001) compared with secondary TMR patients, with a difference of Δ −1.0 at the day of TMR (primary = 4.5, secondary = 5.5), and a difference of Δ −1.4 at the 6-month mark (primary = 3.6, secondary = 5.0). Primary TMR patients also reported significantly lower Pain Interference (p < 0.001) and Pain Intensity scores (p < 0.001) over the complete trajectory of their care.

Conclusion Primary TMR patients report lower pain during the first 6 months postoperatively compared with secondary TMR patients. This may reflect how pre-existing neuropathic pain is more challenging to mitigate through peripheral nerve surgery. The current trends may assist in both understanding the postoperative pain course and managing patient expectations following TMR.

Level of Evidence Therapeutic – IV.

Keywords

targeted muscle reinnervation - neuroma - amputees - PROMs

Funding

This work was in part supported by the Jesse B. Jupiter/Wyss Medical Foundation Endowment. I. L. V. is a consultant for AxoGen Inc, Checkpoint Surgical Inc, and Integra Lifesciences Inc. K. R. E. is a consultant for AxoGen Inc, Checkpoint Surgical Inc, Integra Lifesciences Inc, Tissium, Tulavi Therapeutics Inc, and Biocircuit. F. V. R., Y. A. J. H., B.G.-E., J. M., and M. H. have nothing to disclose.

Publication History

Received: 13 March 2024

Accepted: 12 August 2024

Accepted Manuscript online:
27 August 2024

Article published online:
07 October 2024

• References

• 1 Hwang CD, Hoftiezer YAJ, Raasveld FV. et al. Biology and pathophysiology of symptomatic neuromas. Pain 2024; 165 (03) 550-564
• 2 Cherif F, Zouari HG, Cherif W, Hadded M, Cheour M, Damak R. Depression prevalence in neuropathic pain and its impact on the quality of life. Pain Res Manag 2020; 2020: 7408508
• 3 Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment. J Pain Res 2013; 6: 121-136
• 4 Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain 1983; 17 (03) 243-256
• 5 Chang B, Quan Q, Lu S, Wang Y, Peng J. Molecular mechanisms in the initiation phase of Wallerian degeneration. Eur J Neurosci 2016; 44 (04) 2040-2048
• 6 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
• 7 List EB, Krijgh DD, Martin E, Coert JH. Prevalence of residual limb pain and symptomatic neuromas after lower extremity amputation: a systematic review and meta-analysis. Pain 2021; 162 (07) 1906-1913
• 8 Limakatso K, Bedwell GJ, Madden VJ, Parker R. The prevalence and risk factors for phantom limb pain in people with amputations: a systematic review and meta-analysis. PLoS One 2020; 15 (10) e0240431
• 9 Eberlin KR, Ducic I. Surgical algorithm for neuroma management: a changing treatment paradigm. Plast Reconstr Surg Glob Open 2018; 6 (10) e1952
• 10 Caragher SP, Khouri KS, Raasveld FV. et al. The peripheral nerve surgeon's role in the management of neuropathic pain. Plast Reconstr Surg Glob Open 2023; 11 (05) e5005
• 11 Eberlin KR, Brown DA, Gaston RG. et al. A consensus approach for targeted muscle reinnervation in amputees. Plast Reconstr Surg Glob Open 2023; 11 (04) e4928
• 12 Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA, Stubblefield KA. The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet Orthot Int 2004; 28 (03) 245-253
• 13 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
• 14 Chappell AG, Jordan SW, Dumanian GA. Targeted muscle reinnervation for treatment of neuropathic pain. Clin Plast Surg 2020; 47 (02) 285-293
• 15 Janes LE, Fracol ME, Dumanian GA, Ko JH. Targeted muscle reinnervation for the treatment of neuroma. Hand Clin 2021; 37 (03) 345-359
• 16 Lanier ST, Jordan SW, Ko JH, Dumanian GA. Targeted muscle reinnervation as a solution for nerve pain. Plast Reconstr Surg 2020; 146 (05) 651e-663e
• 17 Mioton LM, Dumanian GA, Shah N. et al. Targeted muscle reinnervation improves residual limb pain, phantom limb pain, and limb function: a prospective study of 33 major limb amputees. Clin Orthop Relat Res 2020; 478 (09) 2161-2167
• 18 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
• 19 Kuiken TA, Barlow AK, Hargrove L, Dumanian GA. Targeted muscle reinnervation for the upper and lower extremity. Tech Orthop 2017; 32 (02) 109-116
• 20 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
• 21 O'Brien AL, Jordan SW, West JM, Mioton LM, Dumanian GA, Valerio IL. Targeted muscle reinnervation at the time of upper-extremity amputation for the treatment of pain severity and symptoms. J Hand Surg Am 2021; 46 (01) 72.e1-72.e10
• 22 Walsh AR, Lu J, Rodriguez E, Diamond S, Sultan SM. The current state of targeted muscle reinnervation: a systematic review. J Reconstr Microsurg 2023; 39 (03) 238-244
• 23 Reid RT, Johnson CC, Gaston RG, Loeffler BJ. Impact of timing of targeted muscle reinnervation on pain and opioid intake following major limb amputation. Hand (N Y) 2024; 19 (02) 200-205
• 24 Gomez-Eslava B, Raasveld FV, Hoftiezer YAJ. et al. Pain sketches to predict pain following primary targeted muscle reinnervation in amputees. Plast Reconstr Surg 2024; 153 (05) 1162-1171
• 25 Raasveld FV, Hao D, Gomez-Eslava B, Hwang CD, Valerio IL, Eberlin KR. Predictive Value of Preoperative Pain Sketches in Lower Extremity Amputees Undergoing Secondary Targeted Muscle Reinnervation for Treatment of Neuropathic Pain. J Am Coll Surg . Published online June 26, 2024;
• 26 Sobti N, Park A, Crandell D. et al. Interdisciplinary care for amputees network: a novel approach to the management of amputee patient populations. Plast Reconstr Surg Glob Open 2021; 9 (02) e3384
• 27 Sheikh S, Fishe J, Norse A. et al. Comparing pain intensity using the numeric rating scale and Defense and Veterans Pain Rating Scale in patients revisiting the emergency department. Cureus 2021; 13 (08) e17501
• 28 Hjermstad MJ, Fayers PM, Haugen DF. et al; European Palliative Care Research Collaborative (EPCRC). Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011; 41 (06) 1073-1093
• 29 Amtmann D, Cook KF, Jensen MP. et al. Development of a PROMIS item bank to measure pain interference. Pain 2010; 150 (01) 173-182
• 30 Chen W-H, Revicki D, Amtmann D, Jensen M, Keefe FCD. Development and analysis of PROMIS Pain Intensity scale. Qual Life Res 2012;20(suppl 1). Available at: https://agerrtc.washington.edu/node/55
• 31 Anhang Price R, Quigley DD, Hargraves JL. et al. A systematic review of strategies to enhance response rates and representativeness of patient experience surveys. Med Care 2022; 60 (12) 910-918
• 32 Farrar JT, Young Jr JP, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001; 94 (02) 149-158
• 33 Chen CX, Kroenke K, Stump TE. et al. Estimating minimally important differences for the PROMIS pain interference scales: results from 3 randomized clinical trials. Pain 2018; 159 (04) 775-782
• 34 Purvis TE, Andreou E, Neuman BJ, Riley III LH, Skolasky RL. Concurrent validity and responsiveness of PROMIS health domains among patients presenting for anterior cervical spine surgery. Spine 2017; 42 (23) E1357-E1365
• 35 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
• 36 Junn A, Dinis J, Reategui A, Liu S, Colen DL, Prsic A. Expanding the criteria for targeted muscle reinnervation: a national assessment of eligibility. Orthoplastic Surg 2022; 7: 7-12 . Available at: https://www.sciencedirect.com/science/article/pii/S2666769X2100035X
• 37 De la Fuente Hagopian A, Farhat S, Doval AF, Reddy NK, Yazid MM, Echo A. Feasibility for immediate targeted muscle reinnervation based on lower extremity amputations trends. Plast Reconstr Surg Glob Open 2023; 11 (04) e4923
• 38 Frantz TL, Everhart JS, West JM, Ly TV, Phieffer LS, Valerio IL. Targeted muscle reinnervation at the time of major limb amputation in traumatic amputees: early experience of an effective treatment strategy to improve pain. JBJS Open Access 2020; 5 (02) e0067
• 39 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (02) 377-381
• 40 Lang TA, Altman DG. Basic statistical reporting for articles published in biomedical journals: the “Statistical Analyses and Methods in the Published Literature” or the SAMPL guidelines. Int J Nurs Stud 2015; 52 (01) 5-9
• 41 de Lange JWD, Hundepool CA, Power DM, Rajaratnam V, Duraku LS, Zuidam JM. Prevention is better than cure: surgical methods for neuropathic pain prevention following amputation - a systematic review. J Plast Reconstr Aesthet Surg 2022; 75 (03) 948-959
• 42 Goodyear EG, O'Brien AL, West JM. et al. Targeted muscle reinnervation at the time of amputation decreases recurrent symptomatic neuroma formation. Plast Reconstr Surg 2023; 153 (01) 154-163
• 43 Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152 (3, Suppl): S2-S15
• 44 Langeveld M, Raasveld F, Hundepool CA. et al. Neuropathic pain after major limb amputation: a cross-sectional study. Plast Reconstr Surg 2024; (e-pub ahead of print)
• 45 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
• 46 Lans J, Groot OQ, Hazewinkel MHJ. et al. Factors related to neuropathic pain following lower extremity amputation. Plast Reconstr Surg 2022; 150 (02) 446-455
• 47 Chang BL, Mondshine J, Fleury CM, Attinger CE, Kleiber GM. Incidence and nerve distribution of symptomatic neuromas and phantom limb pain after below-knee amputation. Plast Reconstr Surg 2022; 149 (04) 976-985
• 48 Chang BL, Hill AL, Mondshine J. et al. Primary targeted muscle reinnervation in above-knee amputations in patients with unsalvageable limbs from limb-threatening ischemia or infection. J Reconstr Microsurg 2024; 40 (02) 109-117
• 49 Raasveld FV, Mayrhofer-Schmid M, Johnston BR. et al. Targeted muscle reinnervation at the time of amputation to prevent the development of neuropathic pain. J Plast Reconstr Aesthet Surg 2024; 97: 13-22
• 50 Langeveld M, Bosman R, Hundepool CA. et al. Phantom limb pain and painful neuroma after dysvascular lower-extremity amputation: a systematic review and meta-analysis. Vasc Endovascular Surg 2024; 58 (02) 142-150
• 51 Althagafi A, Nadi M. Acute Nerve Injury. StatPearls. Published online August 7, 2023. Accessed July 17, 2024 at: https://www.ncbi.nlm.nih.gov/books/NBK549848/
• 52 Moxey PW, Gogalniceanu P, Hinchliffe RJ. et al. Lower extremity amputations–a review of global variability in incidence. Diabet Med 2011; 28 (10) 1144-1153
• 53 Thorud JC, Plemmons B, Buckley CJ, Shibuya N, Jupiter DC. Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review. J Foot Ankle Surg 2016; 55 (03) 591-599
• 54 Smith TJ, Hillner BE. The cost of pain. JAMA Netw Open 2019; 2 (04) e191532-e191532
• 55 Sood R, Stoehr JR, Janes LE, Ko JH, Dumanian GA, Jordan SW. Cell phone application to monitor pain and quality of life in neurogenic pain patients. Plast Reconstr Surg Glob Open 2020; 8 (04) e2732
• 56 Amat M, Duralde E, Masutani R, Glassman R, Shen C, Graham KL. “Patient lost to follow-up”: opportunities and challenges in delivering primary care in academic medical centers. J Gen Intern Med 2022; 37 (11) 2678-2683