Effect of repeated sciatic nerve crush on the conditioning lesion response: Generating an experimental animal model to prolong the denervation period while maintaining peripheral nerve continuity.

Peripheral nerves exhibit long-term residual motor dysfunction following injury. The length of the denervation period before nerve and muscle reconnection is an important factor in motor function recovery. We aimed to investigate whether repeated nerve crush injuries to the same site every 7 days would preserve the conditioning lesion (CL) response and to determine the number of nerve crush injuries required to create an experimental animal model that would prolong the denervation period while maintaining peripheral nerve continuity. Rats were grouped according to the number of sciatic nerve crushes. A significant decrease in the soleus muscle fiber cross-sectional area was observed with increased crushes. After a single crush, macrophage accumulation and macrophage chemotaxis factor CCL2 expression in dorsal root ganglia were markedly increased, which aligned with the gene expression of Ccl2 and its receptor Ccr2. Macrophage numbers, histological CCL2 expression, and Ccl2 and Ccr2 gene expression levels decreased, depending on the number of repeated crushes. Histological analysis and gene expression analysis in the group with four repeated crushes did not differ significantly when compared with uninjured animals. Our findings indicated that repeated nerve crushes at the same site every 7 days sustained innervation loss and caused a loss of the CL response. The experimental model did not require nerve stump suturing and is useful for exploring factors causing prolonged denervation-induced motor dysfunction. SIGNIFICANCE STATEMENT: This study elucidates the effects of repeated nerve crush injury to the same site on innervation and conditioning lesion responses and demonstrates the utility of an experimental animal model that recapitulates the persistent residual motor deficits owing to prolonged denervation without requiring nerve transection and transection suturing.