摘要

Atorvastatin, traditionally used to treat hyperlipidernia, 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-alpha and IL-1 beta levels in DRG and spinal cord. Atorvastatin also inhibited nuclear pNF kappa B activation. Double immunofluorescent staining further demonstrated that pNF kappa B proteins were decreased by atorvastatin in DRG satellite cells and spinal microglia. Atorvastatin may primarily inhibit the nuclear translocation of pNF kappa B to prevent CCI-induced peripheral neuropathic pain. Atorvastatin exhibits antineuroinflammatory and antinociceptive properties in the central and peripheral nerve systems.