AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats
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-scia...
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| Published in | Journal of molecular cell biology Vol. 9; no. 2; pp. 132 - 143 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.04.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1759-4685 1674-2788 1759-4685 |
| DOI | 10.1093/jmcb/mjw043 |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | Pan, Cailong Cheng, Zhixiang Wang, Chaoyu Han, Yuan Liu, Wen-Tao Chen, Lu Hu, Liang Lu, Lijuan Yang, Yanjing |
| Author_xml | – sequence: 1 givenname: Lijuan surname: Lu fullname: Lu, Lijuan organization: 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 – sequence: 2 givenname: Cailong surname: Pan fullname: Pan, Cailong organization: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China – sequence: 3 givenname: Lu surname: Chen fullname: Chen, Lu organization: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China – sequence: 4 givenname: Liang surname: Hu fullname: Hu, Liang organization: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China – sequence: 5 givenname: Chaoyu surname: Wang fullname: Wang, Chaoyu organization: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China – sequence: 6 givenname: Yuan surname: Han fullname: Han, Yuan organization: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China – sequence: 7 givenname: Yanjing surname: Yang fullname: Yang, Yanjing organization: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China – sequence: 8 givenname: Zhixiang surname: Cheng fullname: Cheng, Zhixiang organization: Department of Pain Management & Cancer Biotherapy Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China – sequence: 9 givenname: Wen-Tao surname: Liu fullname: Liu, Wen-Tao organization: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China |
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| SubjectTerms | 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 |
| Title | AMPK activation by peri-sciatic nerve administration of ozone attenuates CCI-induced neuropathic pain in rats |
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