gms | German Medical Science

Objectives/Interrogation: Although peripheral nerve stump (PNS) capping using nerve conduits for the treatment of painful neuroma has attracted attention, details of the underlying mechanisms of pain relief and appropriate nerve conduit length remain unclear. Thus, we aimed to investigate the effectiveness of nerve capping and to identify the appropriate nerve conduit length in a rat neuroma model.

Methods: In male SD rats (n=45), the sciatic nerve (diameter, 1.5 mm) was sharply transected to create a 15 mm nerve defect (rat neuroma model). In the nerve capping (NC) group, the PNS was inserted to a depth of 2 mm into a 3 mm (n = 15) or 6 mm (n = 15) bioabsorbable nerve conduit (internal diameter, 2 mm), whereas in the no capping group (n = 15), no tube was inserted. Autotomy scores were measured to evaluate neuropathic pain, and the PNS was evaluated grossly and histologically at 12 weeks after the surgery. PNS were stained with HE and Masson's trichrome and immunohistochemically stained using anti-neurofilament protein antibody to evaluate the axons, anti-alpha-smooth muscle actin (α-SMA) antibody to evaluate areas of scarring surrounding the PNS, and anti-sigma-1 receptor (S1R) antibody to examine neuroinflammation. Positive areas were morphometrically analyzed using computer-assisted imaging.

Results and Conclusions: At 12 weeks after surgery, the autotomy scores in the 6 mm NC group was significantly lower than that in the no capping group (p < 0.01). In the gross appearance, PNS was swollen and adhered to the surrounding tissues in the no capping group; meanwhile, the PNS remained wrapped with nerve conduits protectively in NC groups. Histologically, neuroma was formed in the no capping group, and regenerating nerves were exposed from the distal end of the nerve conduit in the 3 mm NC group, whereas they converged within the nerve conduit in the 6 mm NC group. Notable perineural scar tissue was found in the no capping and the 3 mm NC group, whereas minimal perineural scar formation was present around the terminated axonal fibers in the 6 mm NC group. Morphometric analysis revealed that the % area of α-SMA and S1R positive expression in the PNS were significantly lower in NC groups than in the no capping group (p < 0.05).

Nerve capping of the PNS using nerve conduits successfully relieved neuropathic pain in the rat neuroma model. Neuroma was not formed, and the peripheral scar formation around the PNS was suppressed. The appropriate length of the nerve conduit is more than 4 times the diameter of the nerve.