Nerve implantation to the muscle after neuroma formation enables pain relief and motor function recovery with reinnervation in rats

Abstract

Aims

Neuroma formation after peripheral nerve injury inhibits functional recovery and contributes to neuropathic pain. This study aimed to evaluate whether nerve implantation into denervated muscle, even after neuroma formation, could promote motor and sensory functional restoration.

Materials and methods

A rat tibial nerve injury model was used. The tibial nerve was ligated and transected to induce neuroma, followed by nerve implantation into the gastrocnemius muscle at 12 days post-injury. Mechanical hypersensitivity was assessed by von Frey testing, and motor function was evaluated using the tibial nerve functional index (TFI). Histological analysis of neuromuscular junctions (NMJ), immunofluorescence of synaptophysin (SYP) in the spinal cord, and electromyography (EMG) were performed to assess reinnervation and synaptic recovery.

Key findings

Nerve implantation significantly reduced mechanical hypersensitivity beginning at 1-week post-implantation and maintained analgesic effects up to 30 weeks. Muscle atrophy was attenuated, and CSA was preserved in the implanted group. NMJ morphology was partially restored, and EMG confirmed partial recovery of neurophysiological muscle contraction beginning at 8 weeks and more clearly at 12 weeks. SYP expression in the ventral horn was significantly preserved at 30 weeks, indicating central modulation of motor signaling. Improvement in TFI supported motor restoration.

Significance

This study demonstrates that delayed nerve implantation into denervated muscle after neuroma formation can achieve motor and sensory recovery through reinnervation. These findings provide insights into the potential effects on nerve-muscle reconstruction treatment for peripheral nerve injury and establish an experimental basis for future clinical application with mechanism studies.