title: Connexin 43 Mediates CXCL12 Production from Spinal Dorsal Horn to Maintain Bone Cancer Pain in Rats.
abstract: Tumor metastasis to bone can subsequently lead to bone cancer pain (BCP). Currently, BCP is difficult to conquer due to a poor understanding of the potential mechanisms. Several studies have indicated that astrocyte-specific connexin 43 (Cx43) was involved in the neuropathic pain, and Cx43 induced the release of chemokine CXCL12 in bone marrow stromal cells. However, whether spinal Cx43 mediates the production of CXCL12 to participate in the maintenance of BCP is still unknown. Here we showed that Walker 256 tumor cells inoculation into the tibia induced a significant mechanical allodynia, which was accompanied by upregulation of spinal p-Cx43 and CXCL12 expression levels from day 6 to day 18 after inoculation. Spinal Cx43 was mainly expressed in astrocytes, and intrathecal (43)Gap26 (a selective Cx43 blocker) markedly attenuated mechanical allodynia as well as reduced p-Cx43 and CXCL12 expression at day 18 after inoculation. Pre-intrathecal administration of CXCL12 almost abolished the attenuated mechanical allodynia by (43)Gap26. Furthermore, intrathecal injection of anti-CXCL12 neutralizing antibody could ameliorate mechanical allodynia with concomitant inhibition of upregulation of CXCL12 expression, but not influence on p-Cx43 expression. Our results indicate that Cx43 mediates CXCL12 production from spinal dorsal horn in astrocytes to maintain bone cancer pain in rats. These findings may improve our understanding of the underlying mechanisms of BCP and provide a novel target for the treatment of BCP.
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: 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: 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: Zu-Min
authors.initials: ZM
authors.lastname: Mao
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, People's Republic of China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Shi
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; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D010812:Physical Stimulation; D017208:Rats, Wistar; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*; D014110:Touch; D015854:Up-Regulation
chemical_list: D057134:Antibodies, Neutralizing; D054377:Chemokine CXCL12; D018031:Connexin 43; C514423:Gap 26 peptide; D010455:Peptides
keywords: Bone cancer pain; CXCL12; Chemokine; Cx43; Spinal dorsal horn