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Nerve Size Mismatch And Sex Differences Influence Analgesic Outcomes Of Targeted Muscle Reinnervation
Madeline Ebert, MD, Lucas Minas, BS, Jose Lucas Zepeda, BS, Gabriella Mraz, BS, Gwendolyn Hoben, MD, PhD.
Medical College of Wisconsin, Milwaukee, WI, USA.
PURPOSE: Targeted muscle reinnervation (TMR) is effective in preventing and treating nerve transection-related pain. This study examines how nerve size mismatch between amputated and recipient nerves influences post-TMR pain outcomes following tibial nerve injury (TNI) in male and female rodents.
METHODS: Forty-eight (24 male, 24 female) Sprague Dawley rats underwent: (1) TNI only, or TMR coaptation to: (2) a single motor branch (TMR-sm), or (3) three motor branches (TMR-multi). Recipient-to-donor size match was ~9% in TMR-sm and ~23% in TMR-multi. Evoked pain behaviors (von Frey, brush, pin, acetone) were assessed biweekly for 16 weeks post-operatively.
RESULTS: In males, von Frey testing demonstrated reduced pain in both TMR groups as compared to TNI (p<0.05) from 6-16 weeks. For brush testing, male TMR-sm and TMR-multi groups exhibited reduced allodynia vs. TNI from 6-16 weeks (p<0.0001). TMR groups also showed less hyperalgesia vs. TNI (p<0.05) with TMR-multi demonstrating less pain than TMR-sm in pin testing. In males, cold hypersensitivity was reduced in the TMR groups versus TNI, with TMR-multi significantly lower than TMR-sm only at 16 weeks. No significant group differences were observed in females for any assay.
CONCLUSION:TMR demonstrated sex-specific effects on pain modulation and minimal influence from size mismatch. In males, TMR-multi improved late cold sensitivity only. These findings highlight the importance of considering sex as a biological variable and suggest that larger recipient nerve capacity may not substantially affect pain outcomes which has important implications clinically when choosing a recipient nerve.
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