Comparative efficacy of acute targeted muscle reinnervation after upper vs. lower limb amputation: A retrospective, global analysis

Background: While targeted muscle reinnervation (TMR) has demonstrated efficacy in reducing chronic pain and symptomatic neuroma formation following limb amputation, differences in outcomes between upper- and lower-limb TMR remain poorly defined. This study compared the efficacy of acute TMR in pain reduction following major upper-versus lower-limb amputation. Methods: A retrospective cohort analysis was conducted using the TriNetX Global Network to identify adults undergoing acute TMR following upper-limb (UL cohort) and lower-limb (LL cohort) amputation. Propensity score matching was performed using demographic and comorbidity covariates. One-year outcomes included new-onset phantom limb pain (PLP), residual limb pain, symptomatic neuroma formation, opioid and neuropathic medication prescriptions, and stump complications. Results: A total of 811 patients met inclusion criteria, with 182 well-matched patients in each cohort. The UL cohort experienced significantly lower rates of PLP (27.5% vs. 40.1%; RR 0.69 [95% CI 0.51-0.92]) and opioid use (59.9% vs. 74.7%; RR 0.80 [95% CI 0.69-0.93]), as well as fewer stump complications (19.8% vs. 34.1%; RR 0.58 [95% CI 0.41-0.83]). RLP (9.9% vs. 7.1%; p = 0.3478) and neuropathic medication use (56.6% vs. 66.5%; p = 0.0525) were similar between cohorts. Conclusions: Acute TMR is associated with significantly lower rates of PLP, opioid use, and stump complications following UL amputation compared with LL amputation. These findings highlight differences in postoperative pain trajectories across patient populations and underscore the need for prospective studies to explore the mechanisms driving these patterns.