title: PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.
abstract: There is accumulating evidence to implicate the importance of EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K), as the downstream effectors, participates in modulation of spinal nociceptive information related to ephrinBs/EphBs. Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal PI3K-p110γ, phosphorylation of AKT (p-AKT) and c-Fos expression. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of spinal AKT induced by ephrinB1-Fc. Inhibition of spinal PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal c-Fos protein expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal PI3K,p-AKT and c-Fos protein. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in spinal. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Yu
authors.forename: Xue-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Jiang
authors.forename: Feng-Jiang
authors.initials: FJ
authors.lastname: Zhang
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D036387:Ephrin-B1 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D059225:Nociception / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D036081:Receptors, Eph Family / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D013997:Time Factors
chemical_list: D036387:Ephrin-B1; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D058539:Phosphatidylinositol 3-Kinase; D036081:Receptors, Eph Family; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases