title: Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model.
abstract: Atorvastatin is an HMG-CoA reductase  inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral  neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity  by inhibition of TGF-beta, pIkB/IkB, NFkB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: L W
authors.initials: LW
authors.lastname: Chu
authors.forename: J Y
authors.initials: JY
authors.lastname: Chen
authors.forename: K L
authors.initials: KL
authors.lastname: Yu
authors.forename: K I
authors.initials: KI
authors.lastname: Cheng
authors.forename: P C
authors.initials: PC
authors.lastname: Wu
authors.forename: B N
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000032:analysis; D009437:Neuralgia / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000069059:Atorvastatin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III