title: Activation of CXCL10/CXCR3 signaling attenuates morphine analgesia: involvement of Gi protein.
abstract: Morphine is a potent agonist of μ-opioid receptor and is widely used to relieve severe pain, including cancer pain. Some chemokines, for example, CX3CL1 and CCL2, participate in the regulation of opioid santinociception. In our previous study, we found overexpression of chemokine CXCL10/CXCR3 in spinal cord participated in the development of cancer-induced bone pain, so we supposed that CXCL10 may have influence in morphine analgesia in cancer pain relief. In this study, we found that a single dose of morphine could transiently increase the expression of CXCL10 in spinal cord. Blocking the function of CXCL10 enhanced morphine antinociception in cancer-induced bone pain rats. However, overexpression of CXCL10 induced acute algesia and decreased the analgesic effect of morphine in normal mice. The algesic effect of CXCL10 was blocked by inhibition of CXCR3 and Gi protein. These results suggested that CXCL10 in spinal cord serves as a novel negative regulator of morphine analgesia and provided evidence that activation of CXCL10/CXCR3 in spinal cord may attenuate antinociceptive potency of morphine in cancer pain relief.
authors.affiliation: Department of Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Ye
authors.forename: Huilian
authors.initials: H
authors.lastname: Bu
authors.forename: Genhua
authors.initials: G
authors.lastname: Guo
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xuehai
authors.initials: X
authors.lastname: Guan
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Xuebi
authors.initials: X
authors.lastname: Tian
authors.forename: Hongbing
authors.initials: H
authors.lastname: Xiang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3; D009020:Morphine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go