Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 mu g). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, andmRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNF alpha, IL1 beta, IL-10, COX-2, preproET-1, gp91(phox), Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anionwere also assessed. Tempol reducedKO(2)-induced mechanical hyperalgesia and thermal hyperalgesia andpawedema. The increasedmRNAexpressionof the evaluatedmediators andoxidative stress in the pawskin and spinal cord and increasedmRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-inducedmolecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.