The Evolution of TMR Utilization: A 23-Year Journey from Exploratory Upper Extremity Prosthesis Control to Standard of Care for Major Amputations and Pain Management

Background: Targeted muscle reinnervation (TMR) has become increasingly utilized beyond advanced myoelectric control to treat and prevent neuropathic pain. This study aims to evaluate changes in practice patterns in TMR utilization. Methods: A single-center, retrospective review was conducted for TMR procedures from 2002 to 2025 using CPT codes and publications. Case volumes were analyzed by major amputation level, timing, and for patients without amputation. A bibliographic analysis from 2004 to 2025 was then conducted to model corresponding research activity. Trends were analyzed using negative binomial regression and logistic regression with α = 0.05. Results: A total of 569 TMR cases were analyzed, including 145 below-knee amputations, 72 above-knee, 102 major upper extremity amputations, and 159 cases for chronic pain in non-amputees. For all-cause indications, there were 196 acute and 373 delayed procedures. Annual TMR volume increased most rapidly from 2016 to 2019, corresponding to new chronic pain applications. Lower extremity cases became and remained more prevalent in 2017, and acute cases became more common in 2025. The proportion of acute TMR cases increased 20% per year (p < 0.001), and the odds of receiving acute TMR for a major amputation increased by 17% per year (p < 0.001). When stratifying by timing for amputation-related cases only, all-cause, limb-specific reoperation was more frequent after acute TMR versus delayed (33/124 (26.6%) vs. 31/192 (16.1%); p = 0.031) with no difference in nerve-specific reoperation (p = 0.25). Notably, on average, only 15% of major amputations received acute TMR from 2021 to 2025. Publishing activity for TMR most rapidly increased from 2018 to 2020. Conclusions: TMR experienced a rapid evolution in both technique and indications through the late 2010s, mirrored by the published literature. Buy-in from referring surgeons is critical to performing acute TMR, which has been demonstrated to have superior outcomes, but careful consideration must be given to mitigate surgical site complications in this population.