It is currently accepted that superoxide anion (O2
•−) is an important mediator in pain and inflammation. The role of
superoxide anion in pain and inflammation has been mainly determined indirectly by
modulating its production and inactivation. Direct evidence using potassium
superoxide (KO2), a superoxide anion donor, demonstrated that it induced
thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be
determined whether KO2 is capable of inducing other inflammatory and
nociceptive responses attributed to superoxide anion. Therefore, in the present
study, we investigated the nociceptive and inflammatory effects of KO2.
The KO2-induced inflammatory responses evaluated in mice were: mechanical
hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot
plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt
pain-like behaviors (flinches, time spent licking and writhing score), leukocyte
recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative
PCR). Administration of KO2 induced mechanical hyperalgesia, thermal
hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching,
and paw licking in a dose-dependent manner. KO2 also induced
time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive,
inflammatory, and oxidative stress components of KO2-induced responses
were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid),
and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In
conclusion, the well-established superoxide anion donor KO2 is a valuable
tool for studying the mechanisms and pharmacological susceptibilities of superoxide
anion-triggered nociceptive and inflammatory responses ranging from mechanical and
thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte
recruitment.