title: Surgical incision induces phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites and GluR1 trafficking in spinal cord dorsal horn via a protein kinase Cγ-dependent mechanism.
abstract: Spinal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor plays an important role in acute pain induced by surgical tissue injuries. Our previous study has shown that the enhanced phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites by protein kinase C (PKC) in the spinal cord dorsal horn is involved in post-surgical pain hypersensitivity. However, which isoforms of PKC are responsible for the phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites remains to be established. In the present study, using an animal model of postoperative pain, we found that surgical tissue injuries enhanced the membrane translocation level of PKCγ, but not PKCα, βI, and βII, and induced the trafficking of GluR1, but not GluR2 into neuronal plasma membrane. Intrathecal (i.t.) pretreatment of small interfering RNA targeting PKCγ to reduce the PKCγ expression in the spinal cord significantly attenuated the pain hypersensitivity and inhibited the phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites as well as GluR1 membrane trafficking. Our study indicates that the surgical incision-induced phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites and GluR1 trafficking are regulated by a PKCγ-dependent mechanism.
authors.affiliation: Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. sincerewy@yahoo.com
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Yue
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D017288:Pain Threshold / Q000502:physiology; D010149:Postoperative Pain / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D011493:Protein Kinase C; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D012694:Serine; C087857:protein kinase C gamma; C104722:glutamate receptor ionotropic, AMPA 2