Tallennettuna:
| Päätekijät: | , , , , , |
|---|---|
| Aineistotyyppi: | Recurso digital |
| Kieli: | |
| Julkaistu: |
Zenodo
2026
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| Aiheet: | |
| Linkit: | https://doi.org/10.5281/zenodo.20063598 |
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Sisällysluettelo:
- PURPOSE: Targeted muscle reinnervation (TMR), a surgical technique coapting transected nerves to a small motor branch, has emerged as a powerful tool to prevent and treat nerve transection and amputation-related pain. Two understudied factors may influence these analgesic benefits: (1) the degree of size mismatch between the amputated nerve and the recipient nerve, and (2) sex differences in pain processing and response. This study investigates how nerve size mismatch influences post-TMR pain relief following tibial nerve injury (TNI) in both male and female rodent models. METHODS: Forty-eight (24 male, 24 female) Sprague Dawley rats were randomly assigned to one of three cohorts: (1) tibial nerve injury (TNI) only, or tibial nerve transection with TMR coaptations: (2) to the motor branch of the semimembranosus (TMR-sm), or (3) to three motor branches (semimembranosus and two branches of biceps femoris; TMR-multi). The recipient to amputated nerve size match was approximately 9% in TMR-sm and 23% in TMR-multi. Evoked pain behaviors (von Frey, dynamic brush, pin, acetone) were performed at baseline and every 2 weeks post-operatively for 16 weeks. RESULTS: von Frey: In males, TNI demonstrated greater mechanical hypersensitivity than TMR-sm (p0.05) and TMR-multi (p0.05), beginning at 6 weeks and persisting through 16 weeks. In females, baseline differences were detected between groups with TMR-sm rats demonstrating increased pain sensitivity. No sustained benefit of TMR-multi over TMR-sm was observed beyond isolated timepoints (10-12 weeks). Brush: In males, TMR-multi animals demonstrated greater allodynia than TMR-sm at early timepoints (2-4 weeks) with no significant differences in allodynia between groups. At 6 weeks, both TMR-sm and TMR-multi demonstrated significantly less allodynia than TNI through 16 weeks (p= 0.0001). In females, allodynia was not observed, and no significant differences were seen across timepoints. Pin: In males, TMR demonstrated significantly less hyperalgesia than TNI beginning at 6 weeks and persisting through 16 weeks (p0.001 TMR-multi, p0.05 TMR-sm). Hyperalgesia behaviors with TMR-multi trended lower than those with TMR-sm. In females, no significant group differences were detected across timepoints. Acetone: In males, noxious response increased significantly at 2 weeks in all groups and remained elevated through 16 weeks in the TNI group. Noxious response in the TMR-sm and TMR-multi groups decreased through 10 weeks. From 12-16 weeks, there was a trend of reduced cold hypersensitivity in TMR-multi compared to TMR-sm but was only significant at 16 weeks. In females, noxious response to acetone increased significantly at 2 weeks and remained elevated through 16 weeks in all groups. CONCLUSION: This study found a clearly sex-specific effect of TMR on pain modulation and only a small effect from varying the size mismatch. In males, TMR-multi only showed a significant improvement from TMR-sm for cold hypersensitivity at the latest time point. This work suggests that analysis of sex as a variable in clinical studies may be needed to better predict outcomes with TMR. While different levels of mismatch merit further study, more than doubling the recipient nerve capacity does not greatly affect pain behaviors in a neuropathic pain injury model. *Source: https://ps-rc.org/meeting/Program/2026/AS36.cgi*