title: Involvement of Spinal CCR5/PKCγ Signaling Pathway in the Maintenance of Cancer-Induced Bone Pain.
abstract: Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China. zjhanglihua@foxmail.com.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Hang
authors.affiliation: Department of Otorhinolaryngology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Shu-Na
authors.initials: SN
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Dan
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shu
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Shao
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000072716:Cancer Pain / Q000188:drug therapy / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D007211:Indoles / Q000008:administration & dosage; D007278:Injections, Spinal; D008301:Maleimides / Q000008:administration & dosage; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019713:Receptors, CCR5 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D019713:Receptors, CCR5; C087857:protein kinase C gamma; D011493:Protein Kinase C; C070515:bisindolylmaleimide I
keywords: CCR5; Cancer-induced bone pain; PKCγ; Signaling pathway