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

Fabiane Y Yamacita-Borin1, Ana C Zarpelon2, Felipe A Pinho-Ribeiro2

  • 1Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM380 PR445, Cx Postal 10.011, Londrina, Paraná, CEP 86057-970, Brazil; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Av. Robert Koch 60, Londrina, Paraná, CEP 86038-350, Brazil.

Neuroscience Letters
|August 21, 2015
PubMed

Insights

Superoxide anion triggers pain and inflammation, which is dependent on tumor necrosis factor-alpha (TNFα) signaling via TNFR1. Inhibiting TNFα/TNFR1 signaling reduces oxidative stress and pain, clarifying their interrelation.

Area of Science:

  • Immunology
  • Neuroscience
  • Biochemistry

Background:

  • Tumor necrosis factor-alpha (TNFα) and superoxide anion production are key mediators of inflammation and pain.
  • Understanding the interplay between TNFα and superoxide anion in pain signaling is crucial for developing effective analgesics.

Purpose of the Study:

  • To investigate if superoxide anion-induced pain relies on TNFα signaling.
  • To determine the role of superoxide anion in TNFα-induced hyperalgesia.
  • To elucidate the interrelation between TNFα and superoxide anion in pain.

Main Methods:

  • Intraplantar injection of a superoxide anion donor (potassium superoxide) in wild-type mice.
  • Assessment of mechanical hyperalgesia, neutrophil recruitment (myeloperoxidase activity), and pain-like behaviors.
  • Utilized tumor necrosis factor receptor 1-deficient (TNFR1-/-) mice and etanercept treatment.
  • Administered Apocynin (NADPH oxidase inhibitor) or Tempol (superoxide dismutase mimetic).

Main Results:

  • Superoxide anion donor induced hyperalgesia, neutrophil recruitment, and pain behaviors in wild-type mice.
  • TNFR1 deficiency and etanercept treatment inhibited superoxide anion-induced pain and oxidative stress.
  • Apocynin or Tempol treatment attenuated TNFα-induced hyperalgesia and neutrophil recruitment.

Conclusions:

  • TNFα/TNFR1 signaling is critical for superoxide anion-induced pain.
  • TNFα/TNFR1 signaling amplifies superoxide anion-induced oxidative stress, sustaining pain and inflammation.
  • Targeting the TNFα/superoxide anion pathway offers a potential strategy for pain management.