Knee　osteoarthritis　(KOA)　is　a　common　and　disabling　condition　characterized　by　attacks　of　pain　around　the　joints,　and　it　is　a　typical　disease　that　develops　chronic　pain.　Previous　studies　have　proved　that　5-HT1,　5-HT2,　and　5-HT3　receptors　in　the　spinal　cord　are　involved　in　electroacupuncture　(EA)　analgesia.　The　5-HT7　receptor　plays　antinociceptive　role　in　the　spinal　cord.　However,　it　is　unclear　whether　the　5-HT7　receptor　is　involved　in　EA　analgesia.　The　5-HT7　receptor　is　a　stimulatory　G-protein　(Gs)-coupled　receptor　that　activates　adenylyl　cyclase　(AC)　to　stimulate　cyclic　adenosine　monophosphate　(cAMP)　formation,　which　in　turn　activates　protein　kinase　A　(PKA).　In　the　present　study,　we　found　that　EA　significantly　increased　the　tactile　threshold　and　the　expression　of　the　5-HT7　receptor　in　the　dorsal　spinal　cord.　Intrathecal　injection　of　5-HT7　receptor　agonist　AS-19　mimicked　the　analgesic　effect　of　EA,　while　a　selective　5-HT7　receptor　antagonist　reversed　this　effect.　Moreover,　intrathecal　injection　of　AC　and　PKA　antagonists　prior　to　EA　intervention　prevented　its　anti-allodynic　effect.　In　addition,　GABA(A)　receptor　antagonist　bicuculline　administered　(intrathecal,　i.t.)　prior　to　EA　intervention　blocked　the　EA　effect　on　pain　hypersensitivity.　Our　data　suggest　that　the　spinal　5-HT7　receptor　activates　GABAergic　neurons　through　the　Gs-cAMP-PKA　pathway　and　participates　in　EA-mediated　inhibition　of　chronic　pain　in　a　mouse　model　of　KOA.