title: MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain.
abstract: Accumulating evidence suggests that chemokine monocyte chemoattractant protein-1 (MCP-1) is significantly involved in the activation of spinal microglia associated with pathological pain, at the same time that the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) pathway localized in spinal microglia is involved in both neuropathic and inflammatory pain. However, whether there is a connection between MCP-1 and the PI3K/Akt pathway and in their underlying mechanisms in bone cancer pain (BCP) has not yet been elucidated. In the current study, we investigated the expression changes of p-Akt in microglia and OX-42 (microglia marker) after being stimulated with MCP-1 in vitro, as well as in a BCP model that was established by an intramedullary injection of mammary gland carcinoma cells(Walker 256 cells) into the tibia of rats. We observed a significant increase in expression levels of p-Akt and OX-42 in microglia as well as in spinal dorsal horns of BCP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody or PI3K inhibitor LY294002 reduced the expression of p-Akt or OX-42, and LY294002 attenuated the mechanical allodynia of BCP rats. These results suggest that MCP-1 may stimulate spinal microglia via the PI3K/Akt pathway in BCP.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: kame_jindi@163.com.
authors.forename: Di
authors.initials: D
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: szyangjp@suda.edu.cn.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: szhujh30@163.com.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: lenawang0303@163.com.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: Brain Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: jzuo919@126.com.
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013977:Tibia
chemical_list: D018932:Chemokine CCL2; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; C111835:CCL2 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Bone cancer pain; MCP-1; Microglia; PI3K; Spine