Atorvastatin Prevents Neuroinflammation in Chronic Constriction Injury Rats through Nuclear NF魏B Downregulation in the Dorsal Root Ganglion and Spinal Cord
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- 作者：Li-Wen Chu ; Jun-Yih Chen ; Pao-Chu Wu ; Bin-Nan Wu
- 刊名：ACS Chemical Neuroscience
- 出版年：2015
- 出版时间：June 17, 2015
- 年：2015
- 卷：6
- 期：6
- 页码：889-898
- 全文大小：648K
- ISSN：1948-7193
文摘
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鈥揇awley 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-伪 and IL-1尾 levels in DRG and spinal cord. Atorvastatin also inhibited nuclear pNF魏B activation. Double immunofluorescent staining further demonstrated that pNF魏B proteins were decreased by atorvastatin in DRG satellite cells and spinal microglia. Atorvastatin may primarily inhibit the nuclear translocation of pNF魏B to prevent CCI-induced peripheral neuropathic pain. Atorvastatin exhibits antineuroinflammatory and antinociceptive properties in the central and peripheral nerve systems.