BackgroundNeuropathic　pain　(NP)　is　a　refractory　disease　in　the　clinic　with　a　tremendous　impact　on　the　quality　of　life　of　patients.　Gene　therapy　is　a　potential　strategy　for　the　management　of　NP.　In　the　present　study,　we　examined　the　analgesic　effect　and　mechanism　of　hepatocyte　growth　factor　(HGF)　in　vitro　and　in　vivo.　MethodsWe　examined　the　proinflammatroy　gene　changes　in　lipopolysaccharide　(LPS)-induced　microglia　BV2　cells　with　a　quantitative　real-time　polymerase　chain　reaction　of　interleukin　(IL)-1,　IL-6,　tumor　necrosis　factor　(TNF)-　and　inducible　nitric　oxide　synthase　(iNOS).　Mechanical　stimulation　tests　were　performed　five　times　at　5-min　intervals　to　assess　pain　thresholds　using　Von　Frey　Hair　in　mice　following　spared　nerve　injury　(SNI).　The　glial　cell　activation　of　spinal　cord　was　examined　by　western　blotting.　Statistical　significance　was　determined　by　a　Tukey＇s　test　and　a　paired　t-test.　ResultsWe　found　that　recombinant　human　HGF　protein　suppressed　LPS-induced　BV2　cell　activation　in　vitro,　marked　by　the　down-regulation　of　IL-1,　IL-6,　TNF-　and　iNOS　expression,　as　well　as　decrease　of　nitric　oxide　production.　Moreover,　intrathecal　injection　of　naked　plasmid　encoding　HGF　gene　(pUDK-HGF)　significantly　attenuated　SNI-induced　pain　behaviors　in　mice　by　direct　inhibition　of　spinal　cord　microglia　and　astrocyte　activation.　ConclusionsThe　results　of　the　present　study　indicate　that　pUDK-HGF　can　reduce　cytotoxicity　products　released　from　activated　glial　cells,　which　may　provide　a　promising　therapeutic　strategy　for　treating　NP.