Abstract

Treatment of painful neuroma remains difficult, despite the availability of numerous surgical procedures. Recently, nerve capping treatment for painful neuroma using artificial nerve conduits has been introduced in clinical and basic research. However, the appropriate length of the nerve conduit and the pain relief mechanism have not been determined. In this study the authors aimed to investigate nerve capping treatment with a bioabsorbable nerve conduit using the rat sciatic nerve amputation model. Using histological analysis, the authors focused on the nerve conduit length and pain relief mechanism. Sixteen Sprague Dawley rats were evaluated for neuropathic pain using an autotomy (self-amputation) score and gross and histological changes of the nerve stump 2, 4, 8, and 12 weeks after sciatic nerve neurectomy without capping. Forty-five rats were divided into 3 experimental groups, no capping (control; n = 15), capping with a 3-mm nerve conduit (n = 15), and capping with a 6-mm nerve conduit (n = 15). All rats were evaluated using an autotomy score and nerve stump histology 12 weeks after neurectomy. The nerve conduit was approximately 0.5 mm larger than the 1.5-mm diameter of the rat sciatic nerves to prevent nerve constriction. The autotomy scores gradually exacerbated with time. Without capping, a typical bulbous neuroma was formed due to random axonal regeneration 2 weeks after neurectomy. Subsequently, the adhesion surrounding the neuroma expanded over time for 12 weeks, and at the 12-week time point, the highest average autotomy scores were observed in the no-capping (control) group, followed by the 3- and the 6-mm nerve conduit groups. Histologically, the distal axonal fibers became thinner and terminated within the 6-mm nerve conduit, whereas they were elongated and protruded across the 3-mm nerve conduit. Minimal perineural scar formation was present around the terminated axonal fibers in the 6-mm nerve conduit group. Expressions of anti-α smooth muscle actin and anti-sigma-1 receptor antibodies in the nerve stump significantly decreased in the 6-mm nerve conduit group. In the rat sciatic nerve amputation model, nerve capping treatment with a bioabsorbable nerve conduit provided relief from neuroma-induced neuropathic pain and prevented perineural scar formation and neuroinflammation around the nerve stump. The appropriate nerve conduit length was determined to be more than 4 times the diameter of the original nerve.

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