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.