title: Atorvastatin attenuates neuropathic pain in rat neuropathy model by down-regulating oxidative damage at peripheral, spinal and supraspinal levels.
abstract: Atorvastatin is an HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease. Oxidative stress is considered to be one of the main causes of neuropathic pain after nerve injury. This study aimed to investigate the effect of atorvastatin on oxidative stress and hyperalgesia in chronic constriction injury (CCI) model of neuropathic pain. Pain behaviour in rats was evaluated before and after atorvastatin administration using mechanical and heat hyperalgesia. The markers for oxidative stress in sciatic nerve, spinal cord and pre-frontal cortex (PFC) area of brain were biochemically detected in vehicle and atorvastatin-treated neuropathic CCI rats. Atorvastatin attenuated hyperalgesia. We found a significant increase in malondialdehyde (MDA), nitric oxide (NO), superoxide anion (O2(-)) and protein carbonyl along with a reduction in catalase (CAT), reduced glutathione (GSH), total thiol (SH) and glutathione-S-transferase (GST) and; increase in superoxide dismutase (SOD) levels in the sciatic nerve, spinal cord and PFC of the CCI-induced neuropathic rats. Reduced levels of enzymatic and non enzymatic antioxidants were restored by atorvastatin. The levels of MDA, O2(-), and protein carbonyl in these tissues were significantly reduced in the atorvastatin-treated CCI rats compared to the untreated CCI rats. Our study demonstrated that atorvastatin attenuates neuropathic pain through inhibition of oxidative stress in sciatic nerve, spinal cord and brain suggesting antioxidants as potential drugs in neuropathic pain management. This study provides a new application of atorvastatin in treatment of neuropathic pain.
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Nitya N
authors: NN
authors: Pathak
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Venkanna
authors: V
authors: Balaganur
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Madhu C
authors: MC
authors: Lingaraju
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Vinay
authors: V
authors: Kant
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Najeeb
authors: N
authors: Latief
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Amar S
authors: AS
authors: More
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Dhirendra
authors: D
authors: Kumar
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors: Dinesh
authors: D
authors: Kumar
authors: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India. Electronic address: sktandan@ivri.res.in.
authors: Surendra K
authors: SK
authors: Tandan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D000069059:Atorvastatin; D015536:Down-Regulation; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin
keywords: Atorvastatin; Chronic constriction injury; Hyperalgesia; Neuropathic pain; Oxidative stress