title: Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats.
abstract: Previously, we showed that activation of the spinal CXCL9, 10/CXCR3 pathway mediated bone cancer pain (BCP) in rats. However, the cellular mechanism involved is poorly understood. Here, we found that the activated CXCR3 was co-localized with either neurons, microglia, and astrocytes in the spinal cord, or non-peptidergic-, peptidergic-, and A-type neurons in the dorsal root ganglion. The inoculation of Walker-256 mammary gland carcinoma cells into the rat's tibia induced a time-dependent phosphorylation of Akt and extracellular signal-regulated kinase (ERK1/2) in the spinal cord, and CXCR3 was necessary for the phosphorylation of Akt and ERK 1/2. Meanwhile, CXCR3 was co-localized with either pAkt or pERK1/2. Blockage of either Akt or ERK1/2 prevented or reversed the mechanical allodynia in BCP rats. Furthermore, there was cross-activation between PI3K/Akt and Raf/MEK/ERK pathway under the BCP condition. Our results demonstrated that the activation of spinal chemokine receptor CXCR3 mediated BCP through Akt and ERK 1/2 kinase, and also indicated a crosstalk between PI3K/Akt and Raf/MEK/ERK signaling pathways under the BCP condition.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Qiao-Chu
authors.initials: QC
authors.lastname: Fu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Dai
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Hui-Lian
authors.initials: HL
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Zhen-Peng
authors.initials: ZP
authors.lastname: Song
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Bing-Rui
authors.initials: BR
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Xiang
authors.affiliation: Department of neurology, Liuzhou Traditional Chinese Medical Hospital, the Third Affiliated Hospital of Guangxi University of Chinese Medicine, 32Jiefang West Road, Liuzhou 545001, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Psychology, Social Work and Human Sciences, University of West London, London, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Manyande
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan 430030, PR China. Electronic address: yktian@tjh.tjmu.edu.cn.
authors.forename: Yu-Ke
authors.initials: YK
authors.lastname: Tian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000502:physiology; D054367:Receptors, CXCR3 / Q000378:metabolism*
chemical_list: C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Bone cancer; CXCR3; ERK; Pain