Antihyperalgesic and Anti-inflammatory Effects of Atorvastatin in Chronic Constriction Injury-Induced Neuropathic Pain in Rats
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Abstract
Atorvastatin is a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor used in treatment of hypercholesterolemia and prevention of coronary heart disease. The aim of this study is to investigate the antihyperalgesic and anti-inflammatory effects of atorvastatin (3, 10, and 30 mg/kg by oral gavages for 14 days) in chronic constriction injury (CCI) model of neuropathic pain in rats. CCI caused significant increase in tumor necrosis factor-α, interleukin 1 beta, prostaglandin E2, along with matrix metalloproteases (MMP-2) and nerve growth factor (NGF) levels in sciatic nerve and spinal cord concomitant with mechanical and thermal hyperalgesia, which were significantly reduced by oral administration of atorvastatin for 14 days as compared to CCI rats. Our study demonstrated that atorvastatin attenuates neuropathic pain through inhibition of cytokines, MMP-2, and NGF in sciatic nerve and spinal cord suggesting that atorvastatin could be an additional therapeutic strategy in management of neuropathic pain.
KEY WORDS
CCI neuropathic pain proinflammatory cytokines MMP-2 NGF atorvastatinAbbreviations
- HMG-CoA
3-Hydroxy-3-methyl-glutaryl-coenzyme A
- CCI
Chronic constriction injury
- TNF-α
Tumor necrosis factor-α
- IL-1β
Interleukin-1 beta
- PGE2
Prostaglandin E2
- MMP-2
Matrix metalloproteases
- NGF
Nerve growth factor
- COX-2
Cyclooxygenase-2
- ELISA
Enzyme-linked immunosorbent assay
- DMSO
Dimethyl sulfoxide
- PWT
Paw withdrawal threshold
- PWL
Paw withdrawal latencies
- DRG
Dorsal root ganglion
- CNS
Central nervous system
- GFAP
Glial fibrillary acidic protein
- SEM
Standard error of means
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