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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.

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Abbreviations

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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  1. Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243 122, India

    Nitya N. Pathak, Venkanna Balaganur, Madhu C. Lingaraju, Amar S. More, Vinay Kant, Dhirendra Kumar, Dinesh Kumar & Surendra Kumar Tandan

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Pathak, N.N., Balaganur, V., Lingaraju, M.C. et al. Antihyperalgesic and Anti-inflammatory Effects of Atorvastatin in Chronic Constriction Injury-Induced Neuropathic Pain in Rats. Inflammation 36, 1468–1478 (2013). https://doi.org/10.1007/s10753-013-9688-x

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