PMID- 28352316 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 13 IP - 2 DP - 2017 Feb TI - Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain. PG - 461-466 LID - 10.3892/etm.2016.3979 [doi] AB - 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. FAU - Liu, Lei AU - Liu L AD - 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. FAU - Gao, Xiu-Juan AU - Gao XJ AD - Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China. FAU - Ren, Chun-Guang AU - Ren CG AD - Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China. FAU - Hu, Ji-Hua AU - Hu JH AD - Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China. FAU - Liu, Xian-Wen AU - Liu XW AD - Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China. FAU - Zhang, Ping AU - Zhang P AD - Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China. FAU - Zhang, Zong-Wang AU - Zhang ZW AD - Department of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China. FAU - Fu, Zhi-Jian AU - Fu ZJ AD - Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China. LA - eng PT - Journal Article DEP - 20161216 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC5348680 OTO - NOTNLM OT - C-C chemokine receptor type 2 OT - bone cancer pain OT - monocyte chemoattractant protein-1 OT - morphine tolerance OT - spinal cord EDAT- 2017/03/30 06:00 MHDA- 2017/03/30 06:01 PMCR- 2016/12/16 CRDT- 2017/03/30 06:00 PHST- 2015/07/17 00:00 [received] PHST- 2016/10/21 00:00 [accepted] PHST- 2017/03/30 06:00 [entrez] PHST- 2017/03/30 06:00 [pubmed] PHST- 2017/03/30 06:01 [medline] PHST- 2016/12/16 00:00 [pmc-release] AID - ETM-0-0-3979 [pii] AID - 10.3892/etm.2016.3979 [doi] PST - ppublish SO - Exp Ther Med. 2017 Feb;13(2):461-466. doi: 10.3892/etm.2016.3979. Epub 2016 Dec 16.