title: Rosuvastatin attenuated the existing morphine tolerance in rats with L5 spinal nerve transection through inhibiting activation of astrocytes and phosphorylation of ERK42/44.
abstract: 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 (ERK(42/44)) and the expressions of TNFα and IL-1β were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.
authors.affiliation: Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China; Department of Anesthesiology, Guangdong Women and Children Hospital, Guangzhou 510010, PR China.
authors.forename: Yongle
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
authors.forename: Lidong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Nanjing College of Clinical Medicine, Southern Medical University, Nanjing210002, PR China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China. Electronic address: liuj_7610@msn.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004361:Drug Tolerance; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013119:Spinal Cord Injuries / Q000209:etiology / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D005464:Fluorobenzenes; D005904:Glial Fibrillary Acidic Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D011743:Pyrimidines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine; D000068718:Rosuvastatin Calcium; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Astrocyte; ERK(42/44); Hyperalgesia; Morphine tolerance; Neuropathic pain; Rosuvastatin