Targeted muscle reinnervation (tmr) vs.regenerative peripheral nerve interface (rpni) in the prevention of post-amputation neuroma and pain: a narrative review of comparative evidence

Abstract

Introduction and objective. Post-amputation pain—phantom limb pain (PLP) and residual limb pain (LPR)—and symptomatic neuroma are common sequelae of limb amputation. Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are two surgical techniques that reorient the severed nerve end toward a physiological target. The objective was to map and characterize the evidence comparing TMR and IPR in limb amputee patients. Methods. A narrative review of the literature was conducted guided by the SANRA criteria. A literature search was conducted in relevant biomedical databases, including MEDLINE/PubMed, Scopus, Web of Science, Embase, and Cochrane Library, restricted to articles published between 2010 and 2026, in English and Spanish. The strategy combined terms related to targeted muscle reinnervation (TMR), regenerative peripheral nerve interface (RPNI), amputation, neuroma, phantom limb pain, and residual limb pain. The selection and synthesis of the evidence was conducted qualitatively, prioritizing primary clinical studies and documents with relevant technical or clinical contribution. Results. Four primary trials met the criteria: a randomized clinical trial of TMR versus standard management, a pilot series of RPNI, a clinical series employing both techniques in forearm amputation, and one population-based study. Overall, they suggest less pain and less neuroma formation with reinnervation compared to standard management or no intervention; however, no studies directly compared RMT with RPNI in humans, and the only direct comparison available is preclinical. Consequently, a comparative effect between techniques was not estimable. Conclusions. There is limited evidence for the benefit of reinnervation over standard management, but evidence on direct comparative efficacy between TMR and RPNI is insufficient. It is recommended to individualize the choice of technique according to the case and the experience of the team, and to refrain from asserting superiority of one over the other until direct comparative tests are available.