Abstract: Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore electrophysiological continuity; (2) prevent distal Wallerian Degeneration and maintain their myelin sheaths; (3) promote primarily motor, voluntary behavioral recoveries as assessed by the Sciatic Functional Index; and, (4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex (e.g., toe twitch) or voluntary behaviors. The preceding companion paper describes sensory terminal field reorganization following PEG-fusion repair of sciatic nerve transections or ablations; however, sensory behavioral recovery has not been explicitly explored following PEG-fusion repair. In the current study, we confirmed the success of PEG-fusion surgeries according to criteria (1–3) above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague–Dawley and inbred Lewis rats. Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws. Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections. Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex. Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats. Following sciatic transection, all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury. However, PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats. Furthermore, PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recovery compared with those without Sciatic Functional Index recovery, suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries. This correlation was independent of the sex or strain of the rat. Furthermore, our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths. No chronic hypersensitivity developed in any rat up to 12 weeks. All these data suggest that PEG-fusion repair of transection peripheral nerve injuries could have important clinical benefits.

Key words: autophagia,  axotomy,  collateral sprouting,  neuropathic pain,  peripheral nerve repair,  polyethylene glycol fusion (PEG-fusion),   saphenous nerve,  sensory neurons,  sex and strain,  Wallerian degeneration