title: Attenuation of morphine analgesic tolerance by rosuvastatin in naïve and morphine tolerance rats.
abstract: Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. Since inflammation in the central nervous system was highly related to morphine tolerance, we sought to investigate whether statins could affect morphine tolerance by mediating glia-derived proinflammatory cytokines secretion. We have undertaken two separate studies: Firstly, we determined the effect of rosuvastatin on naïve rats during induction of morphine tolerance. Secondly, we investigated whether rosuvastation could attenuate the morphine analgesic tolerance in rats that the morphine tolerance established previously. Results demonstrated that peroral rosuvastatin not only delays, but also partially reverses the tolerance to morphine analgesia in rats. The administration of rosuvastatin during induction of morphine tolerance attenuated the activation of ERK and the release of proinflammatory cytokines in the lumbar spinal cord. Similar outcomes were observed in rats were morphine tolerance was established previously. Moreover, our study also found that repeated administration of morphine could activate the astrocytes in the spinal cord while rosuvastation succeeds in suppressing the activation of astrocytes. Our results support the idea that targeting glia-derived proinflammatory effects during morphine treatment is a novel and clinically promising method for enhancing analgesic effects of morphine. We identify a potential new application of statins in the treatment of morphine analgesic tolerance.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Yongle
authors.initials: Y
authors.lastname: Li
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Shu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: He
authors.forename: Weiyan
authors.initials: W
authors.lastname: Li
mesh_terms: D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009020:Morphine; D000068718:Rosuvastatin Calcium