title: Atorvastatin prevents neuroinflammation in chronic constriction injury rats through nuclear NFκB downregulation in the dorsal root ganglion and spinal cord.
abstract: Atorvastatin, traditionally used to treat hyperlipidemia, belongs to a class of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors. This study investigated the antineuroinflammatory and antihyperalgesic effects of atorvastatin in dorsal root ganglia (DRG) and spinal cord for chronic constriction injury (CCI) neuropathic pain in rats. Fifty-four Sprague-Dawley rats were divided into three groups including sham, CCI, and CCI+atorvastatin. Rats were orally administered atorvastatin (10 mg/kg/day) once daily for 2 weeks after surgery and sacrificed at days 3, 7, and 14. All animals were assessed for mechanical allodynia and thermal hyperalgesia in both hindpaws. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to detect inflammatory proteins and proinflammatory cytokines at day 7 after surgery. Pain behaviors were significantly reduced in the CCI+atorvastatin group compared to the CCI group. Atorvastatin attenuated CCI-induced inflammatory mediators (pAkt/Akt, COX-2, iNOS, EP1, and EP4) and reduced proinflammatory cytokines TNF-α and IL-1β levels in DRG and spinal cord. Atorvastatin also inhibited nuclear pNFκB activation. Double immunofluorescent staining further demonstrated that pNFκB proteins were decreased by atorvastatin in DRG satellite cells and spinal microglia. Atorvastatin may primarily inhibit the nuclear translocation of pNFκB to prevent CCI-induced peripheral neuropathic pain. Atorvastatin exhibits antineuroinflammatory and antinociceptive properties in the central and peripheral nerve systems.
authors: Li-Wen
authors: LW
authors: Chu
authors: §Division of Neurosurgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
authors: Jun-Yih
authors: JY
authors: Chen
authors: Pao-Chu
authors: PC
authors: Wu
authors: Bin-Nan
authors: BN
authors: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000276:immunology; D006930:Hyperalgesia / Q000188:drug therapy / Q000276:immunology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology; D015213:Neuroimmunomodulation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D000069059:Atorvastatin
keywords: Atorvastatin; chronic constriction injury; neuroinflammation; neuropathic pain; pNFκB; proinflammatory cytokines