title: Spinal MCP-1 contributes to the development of morphine antinociceptive tolerance in rats.
abstract: 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 μg 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.
authors.affiliation: Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Zhao
authors.forename: Rui-xian
authors.initials: RX
authors.lastname: Guo
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.forename: Jin-lan
authors.initials: JL
authors.lastname: Meng
authors.forename: Li-qiu
authors.initials: LQ
authors.lastname: Mo
authors.forename: Pei-xi
authors.initials: PX
authors.lastname: Chen
authors.forename: Xin-xue
authors.initials: XX
authors.lastname: Liao
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.forename: Jian-qiang
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D004361:Drug Tolerance / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000008:administration & dosage*; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D057134:Antibodies, Neutralizing; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D009020:Morphine