title: AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats.
abstract: Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve. Meanwhile, ozone significantly suppressed CCI-induced activation of spinal microglia. More importantly, the anti-nociceptive effect of ozone depended on the activation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), which was proved by the fact that the phosphorylated AMPK level increased during the ozone therapy and AMPK antagonist abolished the effect of ozone in vivo and in vitro. In addition, direct injection of AMPK agonist could replicate the anti-nociceptive effect of ozone in CCI rats. In conclusion, our observations indicate that peri-sciatic nerve injection of ozone activates AMPK to attenuate CCI-induced neuropathic pain.
authors.affiliation: Department of Pain, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing 210008, China.|Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Cailong
authors.initials: C
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pain Management & Cancer Biotherapy Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002908:Chronic Disease; D003251:Constriction, Pathologic; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007273:Injections, Intramuscular; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology*; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D016194:Receptors, N-Methyl-D-Aspartate; D010126:Ozone; C087857:protein kinase C gamma; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; neuropathic pain; ozone therapy