Islet-cell autoantigen 69 (ICA69), a protein product of human ICA1 or mouse Ical gene,could inhibit glutamate receptor subunit 2 (GIuR2) phosphorylation by interacting with protein interacting with C-kinase 1 (PICK1).By administering stimuli at acupoints corresponding toZusanli (ST36) and Sanyinjiao (SP6) lasting 30mins every other day, electroacupuncture (EA) could alleviate inflammatory hyperalgesia through inhibiting expression of GluR2-phospho(GluR2-p) followingcomplete Freunds adjuvant (CFA) injection in spinal dorsal hom (SDH).Thus, ICA69 might be involved in the anti-hyperalgesic effects of EA in mice.We found that ICA69 mRNA and protein expressioncontents of CFA+EA group which receivedEA treatment were significantly increased compared to that of CFA group by RT-PCR,westernblot and immunohistochemistry.These results suggested that EA enhanced ICA69expression in ipsilateral side of SDH.Then we used ICA69-knockout(KO) mice to study the role of ICA69 in EA analgia.We found that the deficiency of ICA69 induced significant mechanical and thermal withdrawalthreshold in KO-CFA+EA group decrease, compared to WT-CFA+EA group.It suggested that ICA69 was necessary to the anti-hyperalgesic effect of EA.Given that EA could prevent phosphorylation of GluR2, we examined the changes of GluR2-p in ICA69-KO mice.As we expect, ICA69 KO impaired anti-hyperalgesic effects of EA accompanied by increment of GluR2-p.Our findings indicated that spinal ICA69might participate in anti-hyperalgesic effects of EAthrough preventing GluR2phosphorylationand internalization in neurons.