PEG-Fusion Repair After Peripheral Nerve Injuries Enhances Behavioral Recovery and Reduces Self-Mutilation in Rat Models.

Background/Objectives: Self-mutilation behavior is often triggered by neuropathic pain associated with peripheral nerve injuries (PNIs). Polyethylene glycol (PEG)-fusion is a repair method that rapidly joins/fuses the open ends of closely apposed severed axons, greatly reduces Wallerian degeneration, and restores sensorimotor behavior much more rapidly than current clinical procedures. Here, we examined whether the improved sensorimotor behavior recovery following PEG-fusion repair of sciatic nerve injuries compared to Negative Controls (NC) correlated with self-mutilation. We also examined six variables (repair method, behavioral tests, sex, injury type, strain, and surgical experience) that could influence self-mutilation outcomes. Methods: The Sciatic Functional Index (SFI) and the Von Frey (VF) behavioral tests were performed and analyzed. Regression and other analyses were performed to determine the independent effect of six variables on self-mutilation rates and severity. Results: PEG-fused rats that had no self-mutilation had significantly better SFI scores than those that had self-mutilation. More rapid VF sensory recovery in PEG-fused rats was also associated with less self-mutilation. Self-mutilation rates and severity were: (1) significantly reduced following PEG-fusion repairs compared to NCs; (2) significantly increased following weekly VF tests; (3) not different between female and male rats or (4) between simple transection and segmental-loss PNIs; (5) non-existent in Lewis rats and significantly less severe in Sprague Dawley rats than Long Evans rats; and (6) significantly reduced in rats operated on by experienced PEG-fusion surgeons who historically achieved better SFI outcomes than trainee surgeons. Conclusions: Our data suggest potential clinical benefits of PEG-fusion repair to produce more rapid and better sensorimotor recoveries and reductions of self-mutilation behaviors.