Inflammatory　pain　and　neuropathic　pain　are　major　clinical　health　issues　that　represent　considerable　social　and　economic　burden　worldwide.　In　the　present　study,　we　investigated　the　anti-nociceptive　efficacy　of　delivery　of　human　proenkephalin　gene　by　a　plasmid　DNA　vector　(pVAX1-PENK)　on　complete　Freund＇s　adjuvant　(CFA)　induced　inflammatory　pain　and　spared　nerve　injury　(SNI)　induced　neuropathic　pain　in　mice.　Mice　were　intramuscularly　or　intrathecally　administered　pVAX1　or　pVAX1-PENK,　respectively.　Pain　thresholds　in　the　pVAX1-PENK　treated　mice　were　significantly　higher　at　day　3,　then　reached　a　peak　at　day　7　and　lasted　until　day　28　after　gene　transfer,　and　the　analgesic　effect　of　pVAX1-PENK　was　blocked　with　naloxone　hydrochloride.　In　contrast,　pVAX1　treated　mice　did　not　significantly　improve　pain　thresholds.　These　results　indicate　that　peripheral　or　spinal　delivery　of　a　plasmid　encoding　human　proenkephalin　gene　provides　a　potential　therapeutic　strategy　for　inflammatory　pain　and　neuropathic　pain.　(C)　2016　Elsevier　Ireland　Ltd.　All　rights　reserved.