Neuronal regeneration in denervated muscle following sensory and muscular neurotization

Abstract

Background and purpose Neurotization of denervated muscles has been shown to improve muscle bulk, but the neuronal regeneration response has not been compared previously in different surgical techniques of neurotization. Thus, using a rat model of experimental skeletal muscle denervation, we studied neuronal regeneration following sensory neurotization by two methods: sensory nerve to motor branch of muscle and direct sensory nerve implantation to muscle.

Material and methods The lateral head of the gas-trocnemius muscle was denervated in 36 rats, of which the first 12 served as denervated controls. In the second group of 12, the sural nerve was anastomozed to the motor branch of the gastrocnemius muscle (sensory-to-motor nerve neurotization) and in the remaining 12 rats the sural nerve was split into 4 fascicles and embedded into 4 quadrants of the muscle (direct sensory nerve-to-muscle neurotization). Immunohistochemistry was used to examine nerve fibers in muscle containing the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and general neuronal marker protein gene product 9.5 (PGP 9.5).

Results Semiquantitative analysis showed that, compared to the control side, the number of nerve fibers on the experimental side was highest (p < 0.01) for group III (direct sensory nerve-to-muscle neurotization) for all 3 markers. The difference was 71%, 298%, and 254% for PGP 9.5, CGRP, and SP, respectively.

Interpretation This method may be a good option for inducing neuronal regeneration in denervated muscles, and has therapeutic implications for prevention of atrophy of denervated muscles and as an adjunct for reconstruction of soft tissue defects.

Contributions of authors

SN: study design, animal surgery, data analysis, interpretation of results, manuscript preparation. MA: study design, animal anesthesia and surgery, microscopic analysis, interpretation of results, manuscript preparation. RR: care of animals, tissue processing, microscopic analysis, compilation of results. TA: study design, data analysis, manuscript preparation. PH: study design, animal surgery, interpretation of results, manuscript preparation.