AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats

• Published in: Journal of molecular cell biology Vol. 9; no. 2; pp. 132 - 143
• Main Authors: Lu, Lijuan, Pan, Cailong, Chen, Lu, Hu, Liang, Wang, Chaoyu, Han, Yuan, Yang, Yanjing, Cheng, Zhixiang, Liu, Wen-Tao
• Format: Journal Article
• Language: English
• Published: United States 01.04.2017
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Behavior, Animal; Chronic Disease; Constriction, Pathologic; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Injections, Intramuscular; Lipopolysaccharides; Mice; Microglia - drug effects; Microglia - metabolism; Neuralgia - drug therapy; Neuralgia - pathology; NF-kappa B - metabolism; Ozone - administration & dosage; Ozone - pharmacology; Ozone - therapeutic use; Phosphorylation - drug effects; Protein Kinase C - metabolism; Rats, Sprague-Dawley; RAW 264.7 Cells; Receptors, N-Methyl-D-Aspartate - metabolism; Sciatic Nerve - drug effects; Sciatic Nerve - pathology; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Up-Regulation - drug effects; ozone therapy; AMPK; neuropathic pain
• ISSN: 1759-4685; 1759-4685
• DOI: 10.1093/jmcb/mjw043

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.