A disintegrin and a metalloprotease17 (ADAM17), as TNF-α converting enzyme (TACE), cleaves and sheds many membrane-anchored protein and factors, such as TNF-α, Notch, IL-6 receptor and EGF-R ligands. The relationship between these proteins or factors and neuropathic pain is well established. However, whether the ADAM17 has a function in neuropathic pain is not fully understood. The present study is designed to investigate the function of ADAM17 in the development and sustainment during

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... ic pain in rats. The immunofluorescence staining results revealed that ADAM17 primarily expressed in the microglia and IB4 positive neurons in the spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and the expression of ADAM17 was significantly up-regulated in the SDH and DRG in the spinal nerve ligation (SNL) rats. Furthermore, exogenous intrathecal injection of ADAM17 simulates mechanical and thermal hypersensitivity similar to neuropathic pain in normal rats. Moreover, the dominant-negative TNF-α inhibitor selective for soluble TNF-α (solTNF-α), Xpro®1595, 1595 significantly increased 50% paw withdrawal threshold(PWT) of SNL-rats inhibiting the upregulation of ADAM17. Along with the downregulation of ADAM17, the upregulation of TNF-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in SDH was also suppressed. Altogether, these results suggest that ADAM17 participates in the induction and maintenance of neuropathic pain and it may be a potential target for neuropathic pain. Besides, Xpro®1595 could improve SNL-induced neuropathic pain via inhibiting expression levels of ADAM17, TNF-α, IL-1β and IL-6 at SDH.