title: Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer-induced bone pain.
abstract: Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXC chemokine 11 (CXCL11) in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We found that the level of CXCL11 in lumbar spinal cord was increased during the development of morphine tolerance in cancer-induced bone pain rats. Meanwhile, CXCL11 was co-localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by d, l-Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL11. Finally, morphine stimulation could induce the release of CXCL11 by cultured astrocytes and neurons in vitro. In summary, our results provide evidence that spinal CXCL11 plays a powerful modulatory role in the development of morphine tolerance through cross-talking between astrocytes and neurons. Read the Review series "Pain".
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.|Department of Anesthesiology, The Central People's Hospital of Ji'an City, Ji'an, China.
authors.forename: Genhua
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Bingrui
authors.initials: B
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Daiqiang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The first affiliated hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Xuebi
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Psychiatry and Behavioral Science, UT Health Medical School, Houston, Texas, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal; D001859:Bone Neoplasms / Q000150:complications*; D002279:Carcinoma 256, Walker; D054371:Chemokine CXCL11 / Q000235:genetics* / Q000502:physiology*; D004361:Drug Tolerance; D005260:Female; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D054371:Chemokine CXCL11; C515205:Cxcl11 protein, rat; D009020:Morphine
keywords: CXCL11; astrocytes; cancer pain; morphine tolerance; neurons