Targeted muscle reinnervation is associated with significant analgesic-sparing effect in Asian post-amputation patients: Early utilisation and clinical outcomes

Abstract

Purpose

To evaluate early clinical outcomes of targeted muscle reinnervation (TMR) for post-amputation pain in an East Asian population and to describe its utilisation in Hong Kong.

Methods

All patients who underwent major limb amputation with TMR at our institution from January 2017 to December 2024 were reviewed. Fourteen patients (16 TMR procedures) with a minimum of 6 months follow-up were case matched to 16 control patients who underwent major limb amputation without TMR. Primary outcomes were post-amputation pain and analgesic use at latest follow-up (≥6 months). Secondary outcomes included operation time, length of stay (LOS), and 30-day and 90-day readmission and reoperation rates. Territory-wide utilisation of TMR was calculated using Hong Kong Public Hospital data system.

Results

Overall TMR utilisation in Hong Kong was 0.46% (35/7529 major amputations) over 8 years. At latest follow-up, only 5 patients (35.7%) in the TMR group required analgesics, while there were 12 patients (75.0%) requiring analgesics in the control group (P=0.030). Opioid analgesic use (with or without other analgesics) was significantly lower in the TMR group compared with controls (7.1% vs 50.0%; P=0.013). Residual limb pain (RLP), phantom limb pain (PLP) and neuropathic pain were numerically lower in the TMR group but did not reach statistical significance. Operation times, LOS, and 30-day and 90-day readmission and reoperation rates were comparable between groups (P>0.05).

Conclusion

TMR was associated with significantly reduced analgesic use, especially opioids, without increased surgical complications in our cohort of East Asians, verifying that clinical effectiveness of TMR could be reproduced in an Asian locality. Despite growing international evidence supporting TMR, its utilisation in Hong Kong remained very low. Clinician caring for patient with major limb amputation should be aware of the efficacy of TMR and increase its utilisation.

Keywords

targeted muscle reinnervation phantom pain amputation opioid Asian population neuropathic pain residual limb pain

Introduction

Limb amputation remains a life-altering procedure necessitated by severe trauma, malignancy, critical limb ischaemia, or refractory infection. Despite advances in surgical technique and prosthetic technology, post-amputation complications including neuroma formation, residual limb pain (RLP), neuropathic pain, and phantom limb pain (PLP) occur in 15% to 87% of patients.^1,2 These complications pose a substantial challenge to rehabilitation, prosthetic tolerance and quality of life, and are a leading cause of chronic disability and psychological distress.^3,4

Traditional management strategies for post-amputation pain include pharmacological therapy, cognitive behavioural interventions, therapeutic injections, and surgical neuroma excision.^3,4 However, the effectiveness of these approaches remains inconsistent, with no single modality demonstrating clear superiority.⁴ Prolonged opioid use for refractory post-amputation pain carries well-recognised risks of dependence and adverse effects, underscoring the need for more definitive surgical solutions.⁵

Targeted muscle reinnervation (TMR) is a surgical technique that transfers transected peripheral nerve stumps to nearby motor nerve branches of denervated muscles, providing a physiological end-organ for axonal regeneration and thereby reducing symptomatic neuroma formation (Figure 1).^6–10 Originally developed to improve myoelectric prosthesis control in upper limb amputees, TMR has since been extended to lower limb amputation and demonstrated consistent efficacy in both preventing and treating RLP and PLP.^8,11–15 The only randomised controlled trial to date, by Dumanian et al.⁹ reported trends favouring TMR, although results did not reach statistical significance owing to limited sample size. A recent large-scale multicentre propensity-matched study further demonstrated that primary TMR significantly reduces long-term opioid use and opioid dependence up to 3 years post-operatively.⁵ A consensus statement by Eberlin et al.¹⁶ has consolidated the role of TMR in contemporary amputation surgery.

Importantly, the vast majority of existing TMR evidence has been generated in Western, predominantly Caucasian populations. Pain perception, tolerance and expression are influenced by ethnic, cultural and genetic factors.^17,18 Laboratory studies have demonstrated that Asian populations exhibit lower pain thresholds and higher pain sensitivity compared with non-Hispanic White populations, even after controlling for age, sex and socioeconomic status.^17–19 Cultural factors such as stoicism, pain normalisation, and reluctance to report pain or request opioids may further influence post-amputation outcomes and analgesic prescribing patterns in Asian patients.²⁰ To date, no study has specifically examined the clinical outcomes of TMR in an Asian population.

Our institution was the first in Hong Kong, and among the first in East Asia to implement TMR for patients undergoing major limb amputation. This case-matched cohort study aimed to evaluate the early clinical outcomes of TMR in terms of post-amputation pain and analgesic use, assessing its safety and feasibility in a East Asian cohort, and describe the territory-wide utilisation of TMR in Hong Kong. In doing so, we seek to inform clinicians around the asia pacific region, particularly general practitioners managing chronic post-amputation pain and orthopaedic surgeons who perform amputations, that the potential benefits of TMR is reproducible in the Asian population, thus advocating for its broader adoption within the local public healthcare system.

Methods

Study design

This retrospective cohort study included all patients who underwent major limb amputation (upper or lower limb, at or proximal to wrist or ankle) with concurrent or subsequent TMR at our institution from January 2017 to December 2024. Operative diagnoses included musculoskeletal malignancy, limb ischaemia, traumatic amputation, and limb infection. The TMR group was case matched with conventional amputation cases over the same period to form a control group. Control patients were identified from the Clinical Data Analysis and Reporting System (CDARS), a territory-wide database under the Hospital Authority (HA) of Hong Kong. Matching factors included age, gender, operative diagnosis, amputation site (upper vs lower limb), and medical comorbidities. Exact case-matching was challenging owing to the rarity of certain case types; matching was performed as closely as possible, and the two groups showed no statistically significant differences in baseline characteristics. Discrepancies during the case-matching process were settled among authors until consensus was reached. Ethical approval was obtained from the Institutional Review Board (HKU/HA HKW IRB; Ref UW-726).

Patient population

A total of 16 TMR operations were performed in 14 patients (8 males, 6 females) between 2017 and 2024. The control group consisted of 16 patients (9 males, 7 females). All patients had a minimum of 6 months post-operative follow-up. The case summaries were listed in Table 1. Baseline demographics and comorbidities were comparable between groups (Table 2).

Table 1.

Summary of TMR cases.

Case	Gender/age	Nature of disease	Primary operation	Nature of TMR (acute/delayed)	Muscle reinnervation (TMR) performed
1	M/12	Malignancy	Above knee amputation	Acute	tibial nerve to nerve of biceps femoris; common peroneal nerve to nerve of semimembranosus; posterior femoral cutaneous nerve to tibial nerve
2	F/64	Malignancy	Above knee amputation	Acute	tibial nerve to nerve of semimembranosus; common peroneal nerve to nerve of biceps femoris (long head)
3	F/66	Malignancy	Above knee amputation	Acute	common peroneal nerve to nerve of biceps femoris (long head); tibial nerve to nerve of semi-tendinosis; posterior femoral cutaneous nerve to tibial nerve
4	M/73	Malignancy	Below knee amputation	Acute	Tibial nerve to nerve of semitendinosus; deep peroneal and superficial peroneal nerve to nerve of biceps femoris
5*	F/61	Iimb ischaemia	Below Knee amputation (left)	Acute	Tibial nerve to nerve of flexor hallucis longus; superficial peroneal nerve to nerve of peroneus longus; Deep peroneal nerve to nerve of extensor digitorum longus (Figures 2 and 3)
6*		Iimb ischaemia	Below Knee amputation (right)	Acute	Tibial nerve to nerve of flexor hallucis longus; superficial peroneal nerve to nerve of peroneus longus; Deep peroneal nerve to nerve of extensor digitorum longus
7*		Iimb ischaemia	Below Elbow amputation	Acute	ulnar nerve to nerve of flexor carpi ulnaris; median nerve to nerve of flexor digitorum superficialis branch
8	F/46	Malignancy	Below knee amputation	Delayed	Common peroneal nerve to nerve of lateral gastrocnemius; lateral sural nerve to nerve of lateral gastrocnemius; Tibial nerve to nerve of medial gastrocnemius; medial sural nerve to nerve of medial gastrocnemius
9	M/47	Limb ischemia	Below knee amputation	Acute	Deep peroneal nerve to nerve of tibialis anterior; tibial nerve to nerve of soleus; superficial peroneal nerve to nerve of peroneus longus
10	M/62	Malignancy	Shoulder dysarticulation	Delayed	Upper trunk of brachial plexus to spinal accessory nerve; middle trunk to suprascapular nerve; lower trunk to nerve of subclavius
11	F/72	Malignancy	Shoulder dysarticulation	Acute	musculocutaneous nerve to motor branch of clavicular head of pectoralis major; median nerve to motor branch of sternal head of pectoralis major; ulnar nerve to motor branch of sternal head of pectoralis major; radial nerve to thoracodorsal nerve
12	M/13	Malignancy	Interthoracoscapular amputation	Acute	left posterior trunk of brachial plexus to dorsoscapular nerve
13	F/67	Malignancy	Elbow dysarticulation	Delayed	median nerve to musculocutaneous nerve designated to short head of biceps; ulnar nerve to musculocutaneous nerve to designated to brachialis
14	M/63	Malignancy	Below Elbow amputation	Acute	median nerve to nerve to flexor digitorum superficialis; ulnar nerve to nerve to flexor carpi ulnaris; superficial radial nerve to nerve to extensor carpi radialis longus
15	M/58	Traumatic	Above Elbow amputation	Delayed	radial nerve to thoracodorsal nerve; musculocutaneous nerve to clavicular pectoralis major via lateral pectoral nerve; median nerve to lower sternal pectoralis major; ulnar nerve to upper sternal pectoralis major Figure 4
16	M/47	Traumatic	Below Elbow amputation	Delayed	Ulnar nerve to nerve to flexor carpi ulnaris branch

*Cases 5-7 were TMR cases for the same patient. The same patient underwent bilateral BKA and unilateral below elbow amputation, with TMR performed separately for each of the amputated limbs.

Table 2.

Patient demographics and baseline information.

Parameters	TMR group (patient number=14)	Control group (n=16)	P-value
Mean age at surgery ± SD	54.6±18.3	57.7±18.2	0.632^†
Gender, n (%)
Male	8 (57.1%)	9 (56.3%)	0.961*
Female	6 (42.9%)	7 (43.8%)	0.961*
Baseline comorbidities, n (%)
hypertension	4 (28.6%)	5 (31.3%)	0.596*
Diabetes mellitus	4 (28.6%)	4 (25.0%)	0.574*
Hyperlipidemia	3 (21.4%)	1 (6.3%)	0.249*
Chronic pulmonary disease	0 (0%)	1 (6.3%)	0.533*
Chronic kidney disease	3 (21.4%)	3 (18.8%)	0.605*
Mean post-op follow-up duration, months ± SD	42.9±19.2	35.2±49.8	0.571^†

Surgical details	TMR group (operation number= 16)	Control group (n=16)	P-value
Operative diagnosis/nature of disease, n (%)
Musculoskeletal malignancy	10 (62.5%)	8 (50%)	0.446*
infection	0 (0%)	2 (12.5%)
Traumatic amputation	2 (12.5%)	1 (6.3%)
Limb ischemia	4 (25%)	5 (31.3%)
Amputation type, n (%)
Upper limb	8 (50.0%)	4 (25.0%)	0.144*
Lower limb	8 (50.0%)	12 (75.0%)	0.144*
Mean Operation time, mins ± SD
Upper limb operations	302.8±103.7	155.3±115.8	0.078^†
Lower limb operations	165.3±46.9	170.7±106.4	0.881^†

*P-value calculated from chi-square test; fisher-exact test when expected count <5.

^†P-value calculated by independent-samples t-test.

^‡Statistical significance (P<0.05).

Surgical details

There are no universal patient selection criteria for TMR; however, patients with good preoperative functional status, those at risk of post-amputation pain, and those undergoing major limb amputations are generally considered candidates.¹⁶ The principle of TMR is illustrated in Figure 1. There were 11 cases of acute TMR performed concurrently with the primary amputation and 5 cases of delayed (secondary) TMR performed as elective procedures. Acute TMR was defined as TMR performed at the time of the index amputation, while delayed TMR was defined as TMR performed more than 1 month post-operatively. The number and types of nerves transferred were determined preoperatively with reference to published consensus guidelines and established nerve target principles.^12,16 For lower limb amputations, the tibial and peroneal components of the sciatic nerve were commonly targeted; for below-knee amputations, the deep and superficial peroneal nerves were addressed (Figures 2 and 3). For upper limb amputations, particularly above-elbow or shoulder-level procedures, nerves were transferred to motor branches of the pectoralis major, thoracodorsal, and other available recipient muscles (Figure 4). In cases where routine TMR targets were unavailable owing to the extent of resection, the surgeons identified alternative motor nerves in the surrounding region for anastomosis. All procedures were performed by experienced consultant orthopaedic surgeons with microvascular skills.

Study outcomes

Primary outcomes were the incidences of post-amputation pain (RLP, PLP, and neuropathic pain) and analgesic use at latest follow-up (minimum 6 months post-operatively). Phantom limb pain was defined as any noxious phenomenon in which patients experience painful sensation in an amputated limb and was differentiated from stump (residual limb) pain localised to the amputation site.^21,22 Pain was ascertained from clinical records. Different types of analgesics were prescribed at the time of discharge and at the outpatient setting. They included paracetamol, neuropathic agents (e.g. gabapentin, pregabalin), or opioid analgesics. The patients were educated on the use of these different types of analgesic in a stepwise approach. Specialist pain team referrals for refractory post-amputation pain were also recorded. Pain and analgesic outcomes were assessed only at ≥6 months, as early post-operative pain may be confounded by postoperative wound-related discomfort. Secondary outcomes included total operation time, post-operative LOS, and 30-day and 90-day all-cause reoperation and readmission. For patients with delayed TMR, cumulative operation time (primary amputation plus secondary TMR) was used for fair comparison. LOS was compared only for acute TMR patients, as elective delayed TMR patients were typically discharged within 2 days, and their inclusion would have falsely shortened the TMR group average. Overall TMR utilisation in Hong Kong from 2017 to 2024 was calculated as the proportion of TMR procedures among all primary amputations recorded in CDARS.

Statistical analysis

Continuous data were compared using independent-samples t-tests and categorical data using chi-square tests or Fisher exact tests as appropriate. Unadjusted P-values are presented, with two-tailed statistical significance set at P<0.05. All analyses were performed using SPSS Statistics version 29.0 (IBM, USA).

Results

Patient demographics

There were no significant differences in age (54.6±18.3 vs 57.7±18.2 years; P=0.632), gender distribution, operative diagnoses, amputation type, or baseline comorbidities between the TMR and control groups (Table 2). Mean follow-up was 42.9±19.2 months (range 10 to 64) in the TMR group and 35.2±49.8 months (range 6 to 192) in the control group (P=0.571).

Post-amputation pain and analgesic use

At latest follow-up, only 5 patients (35.7%) in the TMR group required analgesics, while there were 12 patients (75.0%) requiring analgesics in the control group (P=0.030). Lists of analgesic combinations of patients in respective groups were listed in supplementary table 1. There was a consistent trend towards reduced pain in the TMR group, although individual pain categories did not reach statistical significance: residual limb pain (28.6% vs 31.3%; P=0.596), phantom limb pain (14.2% vs 31.3%; P=0.256), and neuropathic pain (7.1% vs 12.5%; P=0.552). Opioid use was significantly lower in the TMR group (7.1% vs 50.0%; P=0.013). Use of paracetamol (21.4% vs 37.5%; P=0.290), neuropathic agents (35.7% vs 37.5%; P=0.610), prescription of multiple analgesics (35.7% vs 37.5%; P=0.610), and pain team referrals (7.1% vs 12.5%; P=0.552) were comparable between groups (Table 3). No significant differences in pain or analgesic outcomes were observed between acute and delayed TMR subgroups (P>0.05).

Table 3.

Comparison of post-amputation pain between TMR group and control.

Parameters	TMR group (n=14)	Control group (n=16)	P-value*
Postoperative pain
Stump pain/residual limb pain	4 (28.6%)	5 (31.3%)	0.596
Phantom pain	2 (14.2%)	5 (31.3%)	0.256
Neuropathic pain	1 (7.1%)	2 (12.5%)	0.552
Analgesic use at post-op 6-months
Use of any analgesics	5 (37.5%)	12 (75.0%)	0.030^‡
OTC painkillers (paracetamol)	3 (21.4%)	6 (37.5%)	0.290
Neuropathic agents	5 (35.7%)	6 (37.5%)	0.610
Opioid analgesics (with or without other analgesics)	1 (7.1%)	8 (50.0%)	0.013^‡
Prescription of multiple analgesics	5 (35.7%)	6 (37.5%)	0.610
Pain team referral for post-amputation pain	1 (7.1%)	2 (12.5%)	0.552

*P-value calculated from chi-square test; fisher-exact test when expected count <5.

^‡Statistical significance (P<0.05).

For patients who underwent delayed TMR (n=5), all suffered from phantom limb pain requiring analgesics pre-operatively. Post-operatively, only one had persistent PLP requiring analgesics (pregabalin and amitriptyline) and one had analgesics for persistent stump pain. Clinically, delayed TMR showed promise in resolving chronic PLP (80% with PLP pre-operatively vs 20% post-operatively; P=0.206), although exact benefits should be verified with a larger cohort.

Secondary clinical outcomes

Lower limb operation times were comparable between groups (165.3±46.9 vs 170.7±106.4 mins; P=0.881). Upper limb operation times were longer in the TMR group (302.8±103.7 vs 155.3±115.8 mins; P=0.078) (Table 2). LOS (21.2±14.9 vs 32.4±22.5 days; P=0.148), 30-day and 90-day reoperation, and readmission rates were similar between groups (Table 4). There were no intraoperative complications. Surgical site infection occurred in 2 TMR and 4 control patients. Two patients in each group required reoperation for wound infection within 90 days. Four TMR patients were readmitted within 90 days: suboptimal pain control following delayed TMR in a patient with metastatic osteosarcoma on concurrent chemotherapy (n=1), revision surgery (n=1), infection unrelated to the amputation site (n=1), and unrelated medical issues (n=1). This readmission was arranged for management of tumour pain and concurrent in-hospital chemotherapy rather than TMR failure. Five control patients were readmitted within 90 days for unrelated medical issues (n=3), wound infection (n=1), and chemotherapy (n=1).

Table 4.

Comparison of secondary clinical outcomes between groups.

Parameters	TMR group (n=16)	Control group (n=16)	P-value
Postoperative length of stay, days ± SD	21.2±14.9	32.4±22.5	0.148^†
Reoperation, n (%)
30-day	1 (6.3%)	2 (12.5%)	0.500*
90-day	2 (12.5%)	2 (12.5%)	0.700*
Readmission, n (%)
30-day	3 (18.8%)	5 (31.3%)	0.343*
90-day	4 (25.0%)	5 (31.3%)	0.500*

*P-value calculated from chi-square test; fisher-exact test when expected count <5.

^†P-value calculated by independent-samples t-test.

TMR utilisation in Hong Kong

A total of 7529 primary amputations were performed across Hong Kong from 2017 to 2024. Only 35 TMR procedures were performed during this period, representing an overall utilisation rate of 0.46%.

Discussion

This study verified that clinical effectiveness of TMR could be reproduced in an East Asian population. Our principal findings demonstrated that TMR was associated with a significant reduction in opioid analgesic use at a minimum of 6 months post-operatively, without increasing surgical complications, reoperation, or readmission rates. Despite these encouraging results and growing international evidence, TMR remains severely under-utilised locally.

The significantly lower rate of analgesic (37.5 VS 75.0%; P=0.030) and opioid use in the TMR group (7.1% vs 50.0%; P=0.013) was the most clinically relevant finding of our study. In clinical practice, opioids are typically reserved for post-amputation pain that is refractory to simple analgesia and neuropathic agents; their reduced use therefore serves as a pragmatic proxy for lower overall pain burden.⁵ This finding is consistent with the broader TMR literature. Dumanian et al.⁹ reported trends favouring TMR in their randomised trial, with reductions in PLP (3.2 vs −0.2 pain score reduction; adjusted P=0.06) and RLP (2.9 vs 0.9; adjusted P=0.15) that did not reach significance due to limited sample size. They hypothesised that pain reduction could occur through a physiologic nerve healing mechanism, with the establishment of new afferent nerve signals closing the efferent-afferent feedback loop. A recent multicentre propensity-matched study of 644 TMR patients demonstrated significantly lower risks of opioid use (RR=0.72; 95% CI 0.60–0.86) and opioid dependence (RR=0.50; 95% CI 0.27–0.92) compared with matched controls up to 3 years post-operatively.⁵ Multiple systematic reviews and meta-analyses have consistently reported reductions in PLP, RLP, and analgesic requirements following TMR.^8,11–15 Furthermore, the pain reduction effect of TMR was demonstrated with significant reductions in opioid use in our TMR group, consistent with findings by Chang et al.²³ and Dumanian et al.⁹

While individual pain categories (RLP, PLP, neuropathic pain) were numerically lower in the TMR group, none reached statistical significance. This was expected given our sample size and the use of binary pain outcomes extracted from clinical records, which were inherently less sensitive than continuous pain scores. The consistent direction of effect across all pain categories, combined with the significant opioid reduction based on prescription history, suggests a genuine clinical benefit that this study was underpowered to detect for individual endpoints. Future studies incorporating validated patient-reported outcome measures (PROMs) such as the Patient-Reported Outcomes Measurement Information System (PROMIS) pain scales would provide more sensitive and quantifiable pain assessment.^11,13,14 Utilising TMR as prophylactic treatment rather than therapeutic for chronic pain might potentially prove to be more efficacious, as altered pain perception in chronic pain patients may be difficult to treat.^13,24 Hence, the anticipated effectiveness of TMR may be more significant when conducted in an acute setting.²⁵ While our study found no significant difference between acute and delayed TMR subgroups in terms of analgesic use, the delayed TMR subgroup showed promising results, with 3 out of 4 patients experiencing resolution of pre-operative PLP. Our sample size, however, was too small to draw definitive conclusions, and this should be verified in larger cohorts in the region.

An important consideration is the applicability of TMR outcomes across ethnic groups. Pain perception and tolerance are influenced by ethnicity, with studies demonstrating that Asian individuals exhibit lower pain thresholds and higher pain sensitivity than Caucasian populations.^17–19 Cultural factors including stoicism, pain normalisation, and reluctance to seek opioids are well-documented in East Asian cultures and may affect both pain reporting and analgesic prescribing patterns.²⁰ Despite these known differences, the direction and magnitude of opioid reduction in our Southeast Asian cohort were consistent with published Western data. This suggests that the clinical benefits of TMR are generalisable to Asian populations and supports the applicability of existing international evidence to clinical practice in Hong Kong and possibly the Asia Pacific region. Our study results hold particular significance in the local setting as effectiveness of TMR has previously only been validated in Caucasian populations. The reduction in analgesic consumption further underscores the expanding role of TMR in post-amputation management in the Asian population.

The patient readmitted for suboptimal pain control in the TMR group had metastatic osteosarcoma and was on concurrent chemotherapy. This readmission was related to tumour pain management and chemotherapy scheduling rather than TMR failure. With regards to the early postoperative period following delayed TMR, it was well documented that there is a surge in pain levels within the initial months, which subsequently subsides after approximately 6 months.²⁶ As a result, clinicians should follow up TMR patients more frequently within the early postoperative period and be vigilant of early postoperative pain exacerbation. We now involve the pain team proactively in the immediate postoperative period for all delayed TMR patients to optimise pain management during this transitional phase.

TMR appeared safe as an adjunctive procedure, with comparable complication and reoperation rates to conventional amputation. This was corroborated by the published literature, including a multi-institutional propensity-matched analysis demonstrating no increased risk of major or minor complications following primary TMR.^23,27,28 Notably, lower limb operation times with TMR were comparable to conventional amputation (165.3 vs 170.7 mins; P=0.881), suggesting that TMR adds minimal operative burden when performed by experienced surgeons. Upper limb operation times were longer in the TMR group, reflecting the higher proportion of delayed cases requiring separate incisions and the inherent complexity of upper limb nerve transfers. Comparable operation times, particularly for lower limb procedures, are promising from a health-economic perspective, as they suggested that routine TMR adoption would not substantially increase surgical costs.^5,23 Further cost-effectiveness analysis would be useful to determine the feasibility of implementing TMR across other public hospitals in Hong Kong.²⁹

TMR was heavily under-utilised locally, with only 35 procedures performed since its introduction to our region in 2017. This study aimed to improve the awareness of TMR among clinicians. Suboptimal utilisation could be a result of lack of local expertise, inadequate guidelines for patient selection, and unfamiliarity with a relatively new surgical technique. We suggest that patients with good preoperative functional status who are at risk of post-amputation pain should be routinely considered for TMR.¹⁶ Common indications include management of nerves in acute amputations, treatment of chronic amputation pain, and unreconstructable neuromas.^12,16,30 Major rationales for performing TMR in the lower limbs are improvement of phantom pain and prevention of neuroma formation, while upper limb TMR provides the additional advantage of improving prosthetic limb control.^12,31,32 TMR is a technically demanding procedure with a recognised learning curve.³³ Optimising local expertise through specialised surgeon training is the first step to increasing TMR utilisation in Hong Kong and in East Asia, while clearer indications for TMR would increase the number of eligible patients who benefit from the procedure.³⁴

Limitations

This study has several limitations. First, the small sample size was the principal limitation, although it was comparable to many published TMR series in which cohorts have ranged from 3 to 100 patients.^8,13 The limited number of cases reflected the novelty of TMR in our region and the low local adoption rate; as utilisation increases, future studies with larger cohorts would be better powered to detect differences in individual pain categories. The incidence of phantom limb pain in our locality remains unknown and is difficult to determine, as a significant proportion of amputees may not report or seek treatment for PLP. Our early results call for the need for larger-scale randomised-controlled trials in a local setting to consolidate our knowledge of TMR.³⁰ Second, the use of binary pain outcomes from medical records rather than validated PROMs might underestimate the treatment effect of TMR. Future prospective studies should incorporate standardised instruments such as the PROMIS pain scales.^11,13,14 Third, this single-institution retrospective study, with all procedures performed by experienced consultant surgeons with microvascular skills, limited generalisability and precluded learning curve analysis. A learning curve analysis would be useful in assessing the effect of surgeon experience on surgical time, complication rates, and postoperative outcomes. Fourth, the high proportion of oncological amputations might introduce potential confounders, as tumour-related or metastatic pain may persist after amputation and be difficult to distinguish from post-amputation pain.³⁵ Despite these limitations, our study provided the first evidence that TMR outcomes in an East Asian population are directionally consistent with published international data, supporting the broader applicability of this technique.

Conclusion

TMR was associated with significantly reduced analgesic use, especially opioids, in our cohort of East Asians without increasing surgical complications, verifying that the clinical effectiveness of TMR could be reproducible in an Asian population. TMR was severely under-utilised in Hong Kong, and clinicians caring for patients following amputation and those performing major limb amputations should consider TMR as a viable treatment alternative. With increased clinical utilisation, larger prospective studies with validated outcome measures will be essential to consolidate the evidence base and guide practice in Asia.

Supplemental material

Supplemental material - Targeted muscle reinnervation is associated with significant analgesic-sparing effect in Asian post-amputation patients: Early utilisation and clinical outcomes

Supplemental material for Targeted muscle reinnervation is associated with significant analgesic-sparing effect in Asian post-amputation patients: Early utilisation and clinical outcomes by Kai Chun Augustine Chan, Kelvin Sin Chi Cheung, Raymond CH Yau, Gabriel Ching Ngai Leung, and Margaret Woon Man Fok in Journal of Orthopaedic Surgery.

Footnotes

Acknowledgements

We would like to acknowledge Mr Huntley Chan for the drawing up of the original figure illustrations for this study.

ORCID iDs

Kai Chun Augustine Chan

Raymond CH. Yau

Margaret Woon Man Fok

Ethical considerations

This study was approved by local IRB before commencement (IRB Ref: UW-726).

Author contributions

Kai Chun Augustine CHAN: Conceptualization, methodology, resources, data curation, formal analysis, investigation, writing-original draft, writing-review and editing. Kelvin Sin Chi CHEUNG: Conceptualization, methodology, resources, data curation, formal analysis, investigation, writing-original draft, writing-review and editing. Raymond CH YAU: data curation, resources, writing-review and editing. Gabriel Ching Ngai LEUNG: data curation, resources, writing-review and editing. Margaret Woon Man FOK: Conceptualization, methodology, resources, data curation, project administration, supervision, writing-review and editing. CHAN Kai Chun Augustine and CHEUNG Kelvin Sin Chi are co-first authors with equal contribution. FOK Woon Man Margaret is the senior and corresponding author of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Declaration

This research has not been published previously.

Supplemental material

Supplemental material for this article is available online.

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