期刊
NEUROSCIENCE LETTERS
卷 584, 期 -, 页码 314-319出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2014.11.003
关键词
Rosuvastatin; Morphine tolerance; Neuropathic pain; Hyperalgesia; Astrocyte; ERK42/44
资金
- National Nature Science Foundation of China [30901399]
- Nature Science Foundation of Jiangsu Province [BK20131328]
Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. On day 13, with the establishment of morphine tolerance, rosuvastatin (10 mg/kg) was given o.p. for 5 days. On day 18, lumbar spinal cord was collected immediately after last behavioral testing. The analgesic effect of morphine was determined as the percentage of maximal possible effect (%MPE) after a single morphine (4 mg/kg) injection via tail vein on day 8, 13, and 18. The MPE decreased significantly after administration of morphine to rats with neuropathy for 5 days. Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK42/44) and the expressions of TNF alpha and IL-1(beta) were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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