Does Timing Matter? Long-Term Pain Outcomes Following Prophylactic and Treatment Regenerative Peripheral Nerve Interface (RPNI) Surgery in Major Limb Loss Patients
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2026
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| author | Melanie J. Wang Che-Hsiung Lee Stephen W.P. Kemp Alison K. Snyder-Warwick Theodore A. Kung Paul S. Cederna |
| author_facet | Melanie J. Wang Che-Hsiung Lee Stephen W.P. Kemp Alison K. Snyder-Warwick Theodore A. Kung Paul S. Cederna |
| contents | Purpose: Chronic post-amputation pain is common among the 2 million people in the United States living with limb loss, diminishing function and quality of life. Regenerative Peripheral Nerve Interface (RPNI) surgery is an established approach to neuropathic pain; when performed prophylactically at the index amputation, it has been associated with fewer symptomatic neuromas and improved pain outcomes. Nonetheless, delayed nerve reconstruction is often necessary in practice (e.g., staged wounds, infection, unstable coverage, oncologic priorities, late presentation, limited access), and the optimal timing remains uncertain. This study compares prophylactic (at amputation) versus treatment RPNI with respect to symptomatic neuroma, neuropathic pain, and opioid and other analgesic use. Methods: A cross-sectional, retrospective review was conducted on patients undergoing major limb amputation at a single academic institution from 1970 to 2025. Two cohorts were identified: those who received prophylactic RPNI within 1 month of definitive amputation and those who received treatment RPNI for treatment of symptomatic neuroma pain. Data collected included phantom limb pain (PLP) scores using the Patient-Reported Numeric Rating Scale (NRS), presence of symptomatic neuromas, and analgesic and narcotic use, including opioids, benzodiazepines, antidepressants, and GABAergic medication. Opioid use was recorded in morphine milligram equivalents (MME) per day, and benzodiazepine use was recorded in lorazepam milligram equivalents (LME) per day. Statistical analyses were performed with SPSS using chi square, independent t-test, generalized estimating equation (GEE) and linear mixed-effects model. Results: 302 patients were identified in the prophylactic RPNI group, and 91 patients were identified in the treatment RPNI group (mean follow up time of 38.74 ± 30.82 months). Those in the treatment RPNI group reported higher post-operative PLP scores at 12 months compared to the prophylactic group (p=0.002). There was no PLP in 89% of the patients from the prophylactic group by 1-year postoperatively. Symptomatic neuromas developed in 5% of treatment RPNI patients versus 0.7% in the prophylactic group (p<0.05). At final follow-up, 88% of all patients were not using opioids (91% prophylactic vs. 76% treatment, p<0.05). Linear mixed-effects modeling showed that treatment RPNI patients had higher overall opioid consumption (p<0.001), with significantly higher mean MME/day at 3 and 6 months postoperatively. However, MME/day and LME/day significantly decreased over time in both groups (p<0.05). GABAergic use initially increased postoperatively but decreased significantly by 6 and 12 months (p<0.001) in both groups, with treatment RPNI patients less likely to use GABAergic at 1, 3, and 6 months compared to the prophylactic group (p<0.05). Conclusions: Both prophylactic and treatment RPNI surgery are highly effective in reducing post-amputation pain and opioid use; however, performing RPNI surgery at the time of amputation is associated with lower PLP, opioid consumption, and symptomatic neuroma formation compared to treatment RPNI surgery, supporting early intervention when feasible to optimize long-term outcomes. |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_20101420 |
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| publishDate | 2026 |
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| spellingShingle | Does Timing Matter? Long-Term Pain Outcomes Following Prophylactic and Treatment Regenerative Peripheral Nerve Interface (RPNI) Surgery in Major Limb Loss Patients Melanie J. Wang Che-Hsiung Lee Stephen W.P. Kemp Alison K. Snyder-Warwick Theodore A. Kung Paul S. Cederna plastic surgery reconstructive surgery conference abstract PSRC 2026 Purpose: Chronic post-amputation pain is common among the 2 million people in the United States living with limb loss, diminishing function and quality of life. Regenerative Peripheral Nerve Interface (RPNI) surgery is an established approach to neuropathic pain; when performed prophylactically at the index amputation, it has been associated with fewer symptomatic neuromas and improved pain outcomes. Nonetheless, delayed nerve reconstruction is often necessary in practice (e.g., staged wounds, infection, unstable coverage, oncologic priorities, late presentation, limited access), and the optimal timing remains uncertain. This study compares prophylactic (at amputation) versus treatment RPNI with respect to symptomatic neuroma, neuropathic pain, and opioid and other analgesic use. Methods: A cross-sectional, retrospective review was conducted on patients undergoing major limb amputation at a single academic institution from 1970 to 2025. Two cohorts were identified: those who received prophylactic RPNI within 1 month of definitive amputation and those who received treatment RPNI for treatment of symptomatic neuroma pain. Data collected included phantom limb pain (PLP) scores using the Patient-Reported Numeric Rating Scale (NRS), presence of symptomatic neuromas, and analgesic and narcotic use, including opioids, benzodiazepines, antidepressants, and GABAergic medication. Opioid use was recorded in morphine milligram equivalents (MME) per day, and benzodiazepine use was recorded in lorazepam milligram equivalents (LME) per day. Statistical analyses were performed with SPSS using chi square, independent t-test, generalized estimating equation (GEE) and linear mixed-effects model. Results: 302 patients were identified in the prophylactic RPNI group, and 91 patients were identified in the treatment RPNI group (mean follow up time of 38.74 ± 30.82 months). Those in the treatment RPNI group reported higher post-operative PLP scores at 12 months compared to the prophylactic group (p=0.002). There was no PLP in 89% of the patients from the prophylactic group by 1-year postoperatively. Symptomatic neuromas developed in 5% of treatment RPNI patients versus 0.7% in the prophylactic group (p<0.05). At final follow-up, 88% of all patients were not using opioids (91% prophylactic vs. 76% treatment, p<0.05). Linear mixed-effects modeling showed that treatment RPNI patients had higher overall opioid consumption (p<0.001), with significantly higher mean MME/day at 3 and 6 months postoperatively. However, MME/day and LME/day significantly decreased over time in both groups (p<0.05). GABAergic use initially increased postoperatively but decreased significantly by 6 and 12 months (p<0.001) in both groups, with treatment RPNI patients less likely to use GABAergic at 1, 3, and 6 months compared to the prophylactic group (p<0.05). Conclusions: Both prophylactic and treatment RPNI surgery are highly effective in reducing post-amputation pain and opioid use; however, performing RPNI surgery at the time of amputation is associated with lower PLP, opioid consumption, and symptomatic neuroma formation compared to treatment RPNI surgery, supporting early intervention when feasible to optimize long-term outcomes. |
| title | Does Timing Matter? Long-Term Pain Outcomes Following Prophylactic and Treatment Regenerative Peripheral Nerve Interface (RPNI) Surgery in Major Limb Loss Patients |
| topic | plastic surgery reconstructive surgery conference abstract PSRC 2026 |
| url | https://doi.org/10.5281/zenodo.20101420 |