摘要Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain. Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic. However, no reports have investigated the underlying mechanisms, and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date. In this study, we established a rat model of left sciatic nerve transfection, and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle. Results showed that, compared with rats subjected to nerve stump implantation inside the muscle, rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons, lower expressions of the fibrosis marker α-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump, lower autophagy behaviors, lower expressions of c-fos and substance P, higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia. These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.