title: Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain.
abstract: Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China; Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Zong-Wang
authors.initials: ZW
authors.lastname: Zhang
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Fu
keywords: C-C chemokine receptor type 2; bone cancer pain; monocyte chemoattractant protein-1; morphine tolerance; spinal cord