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Post-Amputation Pain Outcomes After Regenerative Peripheral Nerve Interface (RPNI): A Comparative Analysis by Gender
Melanie J. Wang, MD.
1, Maximilian Wagner, MS
1, Che-Hsiung Lee, MD
1, Ahneesh J. Mohanty, MD
1, Stephen WP Kemp, Ph.D.
1, Paul S Cederna, M.D.
1; Theodore A Kung, MD
2(1)University of Michigan, Ann Arbor, MI, (2)Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI
IntroductionRegenerative Peripheral Nerve Interface (RPNI) surgery is a proven technique for treating post amputation and neuroma pain. Recent animal studies have revealed potential sex-specific differences in pain mitigation after RPNI surgery, suggesting the influence of gender-based nociceptive pathways. These differences have not yet been examined in human studies. Identification of gender-based differences in pain outcomes following RPNI surgery allows for development of individualized pain management regimens.
Methods:
A retrospective single institution study was conducted using DataDirect, the University of Michigan Medicine's clinical database. We analyzed patients who underwent major upper or lower limb amputation between 2015 and 2024 with at least one year of post-operative clinical data. The cohort included male and female patients with and without RPNI surgery. Patients who received prophylactic RPNIs at the time of amputation were compared to those who underwent standard nerve management (i.e. traction neurectomy). Data collected included residual limb pain (RLP) and phantom limb pain (PLP) scores according to Patient-Reported Numeric Rating Scale (NRS), clinical neuroma presence, along with analgesic and narcotic use. Narcotic use was standardized to milligrams morphine equivalents per day (MME/day), while overall analgesic use was quantified using the Medication Quantification Scale version III (MQSIII). Statistical analysis was performed using SPSS.
Results731 patients were identified: 497 males (246 RPNI patients, 251 controls) and 234 females (101 RPNI patients, 133 controls). A significantly higher proportion of females developed chronic post-amputation pain, defined as pain persisting for at least two months following surgery, compared to males in both RPNI and control groups (p<0.001). Among the patients who developed post-amputation pain, 6% of controls had symptomatic neuromas, compared to 0% of RPNI patients (p<0.001). Notably, RLP, PLP, and symptomatic neuroma pain were all significantly less prevalent in the RPNI group compared to controls (p<0.001).
ConclusionsThe observed higher rates of chronic pain in females highlight the importance of individualized approaches and the need to understand sex-based differences in pain pathways. While RPNI surgery is effective in mitigating post-amputation pain overall, these findings underscore the necessity for further research into gender-specific mechanisms that influence pain perception and medication use.
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