PMID- 23187120 OWN - NLM STAT- MEDLINE DCOM- 20130211 LR - 20131121 IS - 1538-2990 (Electronic) IS - 0002-9629 (Linking) VI - 344 IP - 6 DP - 2012 Dec TI - Spinal MCP-1 contributes to the development of morphine antinociceptive tolerance in rats. PG - 473-9 LID - 10.1097/MAJ.0b013e31826a82ce [doi] AB - BACKGROUND: The chemokine monocyte chemoattractant protein-1 (MCP-1) has been shown to contribute to neuropathic pain. However, whether MCP-1 is involved in the development of morphine antinociceptive tolerance is incompletely understood. METHODS: Morphine antinociceptive tolerance was induced by intrathecal administration of 15 mug of morphine daily for 7 days. Immunohistochemistry was used to test the changes in the morphology of spinal MCP-1 immunoreactivity and OX-42-IR. The role of MCP-1 in morphine antinociceptive tolerance is explored by hot-water tail-flick test. RESULTS: Our findings showed that intrathecal chronic morphine exposure obviously increased MCP-1 immunoreactivity in the spinal cord. Moreover, the increased MCP-1 immunoreactivity was observed mainly in the spinal neurons. Intrathecal injections of MCP-1-neutralizing antibody significantly reduced the development of morphine antinociceptive tolerance, suggesting that spinal neuronal MCP-1 contributes to tolerance to morphine antinociception. Treatment with MCP-1-neutralizing antibody also reduced the spinal microglial activation induced by chronic morphine treatment. CONCLUSIONS: This study revealed for the first time that spinal neuronal MCP-1 is a key mediator of the spinal microglial activation and that spinal MCP-1 is involved in morphine antinociceptive tolerance. Inhibition of MCP-1 may provide a new therapy for morphine tolerance management. FAU - Zhao, Chun-mei AU - Zhao CM AD - Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China. FAU - Guo, Rui-xian AU - Guo RX FAU - Hu, Fen AU - Hu F FAU - Meng, Jin-lan AU - Meng JL FAU - Mo, Li-qiu AU - Mo LQ FAU - Chen, Pei-xi AU - Chen PX FAU - Liao, Xin-xue AU - Liao XX FAU - Cui, Yu AU - Cui Y FAU - Feng, Jian-qiang AU - Feng JQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Med Sci JT - The American journal of the medical sciences JID - 0370506 RN - 0 (Analgesics, Opioid) RN - 0 (Antibodies, Neutralizing) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 76I7G6D29C (Morphine) SB - IM MH - Analgesics, Opioid/*administration & dosage MH - Animals MH - Antibodies, Neutralizing/administration & dosage MH - Chemokine CCL2/antagonists & inhibitors/immunology/*physiology MH - Drug Tolerance/*physiology MH - Immunohistochemistry MH - Male MH - Microglia/drug effects/physiology MH - Morphine/*administration & dosage MH - Nociception/drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord/drug effects/*physiology MH - Up-Regulation/drug effects EDAT- 2012/11/29 06:00 MHDA- 2013/02/12 06:00 CRDT- 2012/11/29 06:00 PHST- 2012/11/29 06:00 [entrez] PHST- 2012/11/29 06:00 [pubmed] PHST- 2013/02/12 06:00 [medline] AID - S0002-9629(15)30788-6 [pii] AID - 10.1097/MAJ.0b013e31826a82ce [doi] PST - ppublish SO - Am J Med Sci. 2012 Dec;344(6):473-9. doi: 10.1097/MAJ.0b013e31826a82ce.