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Donor-Recipient Nerve Size Mismatch in Targeted Muscle Reinnervation: A Feature or Flaw for Analgesia and Neuron Survival?
Jose Lucas Zepeda, BS
1, Gabriella Mraz, BS
1, Lucas Minas, BS
1; Gwendolyn Hoben, MD, PhD
2(1)Medical College of Wisconsin, Milwaukee, WI, (2)Clement J. Zablocki VA Medical Center, Milwaukee, WI
Introduction Targeted Muscle Reinnervation (TMR) is a surgical technique designed to facilitate prosthetic control found to prevent amputation-related pain. An understudied feature of TMR is the size mismatch between large, mixed motor sensory nerves and smaller motor nerve branches. Despite clinical evidence showing TMR's efficacy in pain reduction, it remains unclear whether improved size match enhances analgesic outcomes. This study investigates how varying levels of nerve size discrepancy influences pain behaviors and sensory neuron preservation following tibial nerve injury (TNI).
Materials & Methods
Twenty-four male Sprague Dawley rats were randomly assigned into three cohorts: (1) TNI only, (2) TMR with the tibial nerve coapted to the motor branch to semimembranosus (large size mismatch, TMRsm), and (3) TMR with the tibial nerve coapted to 3 motor branches to improve the size match (branches to semimembranosus and 2 branches to biceps femoris, Multi TMR). The donor-to-recipient size match was approximately 9.3% in TMRsm and 23.3% in Multi-TMR. Behavioral assessments were conducted every two weeks from baseline to 16 weeks including von Frey (mechanical hypersensitivity), acetone (cold hypersensitivity), pin test (hyperalgesia), and brush test (allodynia). Retrograde labeling was used to assess sensory neuron retention. Both TMRsm and Multi TMR significantly reduced allodynia, mechanical, cold, and pin hypersensitivity compared to TNI by week two (p < 0.05). However, Multi TMR and TMRsm diverged in allodynia at weeks two (p = 0.003) and four (p = 0.025), with Multi TMR showing higher noxious responses that resolved by week six. By 12 weeks, pain behaviors for both TMR groups were reduced compared to TNI and not significantly different from each other. DRG analysis revealed a significantly higher mean sensory neuron count in Multi-TMR (946 ± 326) compared to TMRsm (212 ± 127) and TNI (627 ± 222), approaching values seen in normal controls (1058 ± 508).
Conclusion This study provides the first in vivo evaluation of nerve size mismatch in TMR, demonstrating that while both TMR approaches improve pain behaviors compared to TNI alone, size-matched Multi-TMR more robustly preserves DRG sensory neurons. These findings suggest that improved nerve size matching may have utility in the future as sensory components for prosthetics continue to develop. However, contrary to traditional nerve repair dogma, size match is not critical to pain reduction.
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