title: Activation of the cAMP-PKA signaling pathway in rat dorsal root ganglion and spinal cord contributes toward induction and maintenance of bone cancer pain.
abstract: The objective of this study was to explore the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling in the development of bone cancer pain in rats. Female Sprague-Dawley rats (N=48) were divided randomly into four groups: sham (n=8), tumor cell implantation (TCI) (n=16), TCI+saline (n=8), and TCI+PKA inhibitor (n=16). Bone cancer-induced pain behaviors - thermal hyperalgesia and mechanical allodynia - were tested at postoperative days -3, -1, 1, 3, 5, 7, 10, and 14. A PKA inhibitor, Rp-cAMPS (1 mmol/l/20 μl), was injected intrathecally on postoperative days 3, 4, and 5 (early phase) or 7, 8, and 9 postoperative days (late phase). The expression of PKA mRNA in dorsal root ganglia (DRG) was detected by reverse transcription-PCR. The concentration of cAMP and activity of PKA in DRG and spinal cord were measured by enzyme-linked immunosorbent assay. TCI treatment induced significant pain behaviors, manifested as thermal hyperalgesia and mechanical allodynia. Spinal administration of the PKA inhibitor Rp-cAMPS during the early phase and late phase significantly delayed or reversed, respectively, TCI-induced thermal hyperalgesia and mechanical allodynia. TCI treatment also led to obvious tumor growth and bone destruction. The level of PKA mRNA in the DRG, as well as the concentration of cAMP and the activity of PKA, in both the DRG and spinal cord were significantly increased after TCI treatment (P<0.01). We conclude that the inhibition of the cAMP-PKA signaling pathway may reduce bone cancer pain.
authors: aDepartment of Anesthesiology, Center for Clinical Research and Translational Medicine, Liangyungang City Dongfang Hospital bDepartment of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Jiangsu cDepartment of Anesthesiology, the Third Affiliated Hospital of Peking University dNeuroscience Research Institute and Center for Pain Medicine, Peking University, Beijing, China.
authors: Gui-Qin
authors: GQ
authors: Zhu
authors: Su
authors: S
authors: Liu
authors: Duan-Duan
authors: DD
authors: He
authors: Yue-Peng
authors: YP
authors: Liu
authors: Xue-Jun
authors: XJ
authors: Song
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014110:Touch
chemical_list: D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases