Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) for pain prevention in patients with limb amputation: A protocol for a systematic review and meta-analysis

Introduction: Regenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) have demonstrated superior outcomes compared to classical amputation in prophylactic prevention of pain, primarily by reducing the incidence of symptomatic neuromas, residual limb pain, and phantom limb pain. However, direct comparisons between these two techniques remain limited. Furthermore, their comparative effectiveness across diverse patient demographics (including age, sex, and comorbidities) and surgical variables (amputation level, etiology, and nerve handling) has not been systematically evaluated. Therefore, the objective of this systematic review and meta-analysis is to synthesize the available evidence to determine the comparative safety and efficacy of primary TMR or RPNI. Methods and design: This review will be conducted following the methodological guidance of the Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive electronic search will be performed in the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, PubMed, and MedRxiv, without language restrictions. We will include randomized controlled trials, quasi-randomized trials, and observational studies. Study selection and data extraction will be managed using Covidence. Two reviewers will independently screen titles and abstracts, assess full-text eligibility, evaluate risk of bias, and extract data. Ethics and dissemination: As this systematic review relies on the analysis of secondary data from published studies, ethical approval is not required. Findings will be disseminated through publication in a peer-reviewed journal and presented at relevant conferences. PROSPERO registration number: CRD42024617299