A review of pain outcomes following targeted muscle reinnervation in lower extremity limb pain

Abstract

Approximately 75% experience phantom (PLP), residual (RLP), or general (GLP) limb pain following lower extremity amputation. Targeted muscle reinnervation (TMR) is a peripheral nerve transfer that reroutes amputated nerves to motor endplates that can prevent or treat limb pain. This systematic review summarizes pain outcomes following primary and secondary treatment of lower extremity PLP, RLP, and GLP. Primary literature review of three databases - PubMed, EMBASE, MEDLINE - were used for all articles related to TMR and lower extremity limb pain, querying the same keywords: “targeted muscle reinnervation” AND “pain”. Citations were then reviewed and eliminated if only upper extremities were studied or the study lacked pain outcomes. Citations were categorized as primary or secondary TMR. Pain outcomes, including Numerical Rating Scales (NRS) and Patient-Reported Outcome Measurement Information System (PROMIS) Pain scores, were aggregated when appropriate. Ten studies met all inclusion and exclusion criteria after formal review for a total of 431 extremities, of which 79.1% (n = 341 limbs) were lower extremities. Average primary TMR PROMIS scores for PLP and RLP were lower than amputees without primary TMR. Average NRS scores and PROMIS Pain scores in secondary TMR demonstrated improvements in PLP, RLP, and GLP. Primary and Secondary TMR does prevent and improve PLP, RLP, and GLP; however, a minority of studies report quantifiable pain outcomes. All future TMR studies should include validated pain outcomes to better quantify the expected pain and quality of life improvements after lower extremity TMR.

Keywords

Lower extremity / amputation / phantom limb pain / residual limb pain / targeted muscle reinnervation / nerve transfer

References

[1] Mioton LM.Targeted muscle reinnervation and prosthetic rehabilitation after limb loss.J Surg Oncol2018;118:807-14

[2] Ephraim PL,MacKenzie EJ,Pezzin LE.Phantom pain, residual limb pain, and back pain in amputees: results of a national survey.Arch Phys Med Rehabil2005;86:1910-9

[3] Hsu E.Postamputation pain: epidemiology, mechanisms, and treatment.J Pain Res2013;6:121-36 PMCID:PMC3576040

[4] Jensen TS,Nielsen J.Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation.Pain1983;17:243-56

[5] Montoya P,Grulke N,Taub E.The relationship of phantom limb pain to other phantom limb phenomena in upper extremity amputees.Pain1997;72:87-93

[6] Collins KL,Schumacher PJ.A review of current theories and treatments for phantom limb pain.J Clin Invest2018;128:2168-76 PMCID:PMC5983333

[7] Mioton LM,Shah N.Targeted muscle reinnervation improves residual limb pain, phantom limb pain, and limb function: a prospective study of 33 major limb amputees.Clin Orthop Relat Res2020;478:2161-7 PMCID:PMC7431223

[8] McNamara CT.Targeted muscle reinnervation: outcomes in treating chronic pain secondary to extremity amputation and phantom limb syndrome.J Reconstr Microsurg2020;36:235-40

[9] Kuiken TA,Lipschutz RD,Stubblefield KA.The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee.Prosthet Orthot Int2004;28:245-53

[10] Hijjawi JB,Lipschutz RD,Stubblefield KA.Improved myoelectric prosthesis control accomplished using multiple nerve transfers.Plast Reconstr Surg2006;118:1573-8

[11] Page MJ,Bossuyt PM.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.BMJ2021;372:n71 PMCID:PMC8005924

[12] PROMIS. Available from: https://www.healthmeasures.net/score-and-interpret/interpret-scores/promis [Last accessed on 27 Sep 2022]

[13] PROMIS Scoring Manuals. Available from: https://staging.healthmeasures.net/score-and-interpret/calculate-scores/223-promis-scoring-manuals [Last accessed on 27 Sep 2022]

[14] Chang BL,Mondshine J.Targeted muscle reinnervation to expendable motor nerves for the treatment of refractory symptomatic neuromas in nonamputees.Plast Reconstr Surg Glob Open2021;9:e3436 PMCID:PMC7929572

[15] Valerio IL,Jordan SW.Preemptive treatment of phantom and residual limb pain with targeted muscle reinnervation at the time of major limb amputation.J Am Coll Surg2019;228:217-26

[16] Frantz TL,West JM,Phieffer LS.Targeted muscle reinnervation at the time of major limb amputation in traumatic amputees: early experience of an effective treatment strategy to improve pain.JB JS Open Access2020;5:e0067 PMCID:PMC7418908

[17] Alexander JH,West JM.Targeted muscle reinnervation in oncologic amputees: early experience of a novel institutional protocol.J Surg Oncol2019;120:348-58 PMCID:PMC7701996

[18] Hoyt BW,Potter BK.Practice patterns and pain outcomes for targeted muscle reinnervation: an informed approach to targeted muscle reinnervation use in the acute amputation setting.J Bone Joint Surg Am2021;103:681-7

[19] Pet MA,Friedly JL,Smith DG.Does targeted nerve implantation reduce neuroma pain in amputees?.Clin Orthop Relat Res2014;472:2991-3001 PMCID:PMC4160473

[20] Chang BL,Attinger CE.Targeted muscle reinnervation improves pain and ambulation outcomes in highly comorbid amputees.Plast Reconstr Surg2021;148:376-86

[21] Dumanian GA,Mioton LM.Targeted muscle reinnervation treats neuroma and phantom pain in major limb amputees: a randomized clinical trial.Ann Surg2019;270:238-46

[22] Kang NV,Michno DA,Tan J.A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective.J Plast Reconstr Aesthet Surg2022;75:960-9

[23] Ferreira-Valente MA,Jensen MP.Validity of four pain intensity rating scales.Pain2011;152:2399-404

[24] Gordon DB.Acute pain assessment tools: let us move beyond simple pain ratings.Curr Opin Anaesthesiol2015;28:565-9

[25] Revicki DA,Harnam N.Development and psychometric analysis of the PROMIS pain behavior item bank.Pain2009;146:158-69 PMCID:PMC2775487

[26] Amtmann D,Jensen MP.Development of a PROMIS item bank to measure pain interference.Pain2010;150:173-82 PMCID:PMC2916053

[27] Resnik L.Reliability of outcome measures for people with lower-limb amputations: distinguishing true change from statistical error.Phys Ther2011;91:555-65

[28] McCarberg B.Pain pathways and nervous system plasticity: learning and memory in pain.Pain Med2019;20:2421-37

[29] Farrar JT,Lamoreaux L,Poole MR.Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.Pain2001;94:149-58

[30] Valerio I,West J,Eberlin KR.Targeted muscle reinnervation combined with a vascularized pedicled regenerative peripheral nerve interface.Plast Reconstr Surg Glob Open2020;8:e2689 PMCID:PMC7253250