Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice.

Abstract

Inhibition of tumor necrosis factor-alpha (TNFα) and superoxide anion production reduces inflammation and pain. The present study investigated whether superoxide anion-induced pain depends on TNFα signaling and the role of superoxide anion in TNFα-induced hyperalgesia to clarify the interrelation between these two mediators in the context of pain. Intraplantar injection of a superoxide anion donor (potassium superoxide) induced mechanical hyperalgesia (0.5-5h after injection), neutrophil recruitment (myeloperoxidase activity), and overt pain-like behaviors (paw flinching, paw licking, and abdominal writhings) in wild-type mice. Tumor necrosis factor receptor 1 deficiency (TNFR1-/-) and treatment of wild-type mice with etanercept (a soluble TNFR2 receptor that inhibits TNFα actions) inhibited superoxide anion-induced pain-like behaviors. TNFR1(-/-) mice were also protected from superoxide anion donor-induced oxidative stress, suggesting the role of this pathway in the maintenance of oxidative stress. Finally, we demonstrated that Apocynin (an NADPH oxidase inhibitor) or Tempol (a superoxide dismutase mimetic) treatment inhibited TNFα-induced paw mechanical hyperalgesia and neutrophil recruitment (myeloperoxidase activity). These results demonstrate that TNFα/TNFR1 signaling is important in superoxide anion-triggered pain and that TNFα/TNFR1 signaling amplifies the oxidative stress triggered by superoxide anion, which contributes to sustaining pain and inflammation.

• Authors: Fabiane Y Yamacita-Borin, Ana C Zarpelon, Felipe A Pinho-Ribeiro, Victor Fattori, Jose C Alves-Filho, Fernando Q Cunha, Thiago M Cunha, Rubia Casagrande, Waldiceu A Verri Jr
• Journal: Neuroscience letters (Neurosci Lett) Vol. 605 Pg. 53-8 (Sep 25 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 26291484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Receptors, Tumor Necrosis Factor, Type I
• Tnfrsf1a protein, mouse
• Tumor Necrosis Factor-alpha
• Superoxides
• potassium superoxide
• Peroxidase
• Etanercept

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Etanercept (pharmacology)
• Hyperalgesia (metabolism, physiopathology)
• Inflammation (immunology, metabolism, physiopathology)
• Lipid Peroxidation
• Mice
• Mice, Inbred C57BL
• Neutrophils (physiology)
• Oxidative Stress
• Pain (metabolism, physiopathology)
• Peroxidase (metabolism)
• Physical Stimulation
• Receptors, Tumor Necrosis Factor, Type I (genetics, metabolism)
• Superoxides (metabolism)
• Touch
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism, pharmacology)