Related Experiment Video
Updated: Jul 7, 2026

Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
Published on: March 15, 2024
Active Nerve Management in Amputation: RPNI as a Strategy to Eliminate Neuroma Formation and Transform Postamputation
Gordana Georgieva1, Gjorgje Dzokikj1, Nikola Gramatnikovski2
11University Clinic for Plastic and Reconstructive Surgery, SkopjeRN Macedonia.
Abstract:
Background: Symptomatic neuroma formation and chronic post-amputation pain remain major barriers to functional recovery following lower limb amputation. Active nerve management strategies, such as the Regenerative Peripheral Nerve Interface (RPNI), have emerged as promising techniques for preventing neuropathic pain by providing a biological target for transected nerves. Methods: A retrospective observational study was conducted including 24 adult patients who underwent transfemoral or transtibial amputation. Twelve patients received prophylactic RPNI at the time of amputation, while 12 underwent standard amputation without active nerve management. Incidence of symptomatic neuroma, Tinel's sign, pain intensity (VAS), pain interference (PROMIS Pain Interference 8a) and prosthetic use were evaluated over a 12-week follow-up period. Results: No cases of symptomatic neuroma were observed in the RPNI group (0%), compared to 66.7% in the control group (p < 0.001). At 12 weeks, mean VAS pain scores were significantly lower in the RPNI group (0.4 ± 0.8) compared to controls (5.8 ± 1.7; p < 0.0001). PROMIS Pain Interference scores at 3 months were markedly improved in the RPNI group (44.0 ± 4.5) versus the control group (66.0 ± 5.8; p < 0.001). A higher proportion of RPNI patients successfully used a prosthesis (66.7% vs. 41.7%), although this difference did not reach statistical significance. Conclusion: Prophylactic RPNI during lower limb amputation effectively prevents symptomatic neuroma formation and significantly reduces post-amputation pain, with favorable functional outcomes. These findings support routine active nerve management as a strategy to optimize rehabilitation and quality of life in amputee patients.
