A novel antioxidant alleviates heat hyperalgesia in rats with an experimental painful peripheral neuropathy

Rats with an experimental painful peripheral neuropathy (the chronic injury (CCI) model) display heat-evoked hyperalgesia. There is now considerable evidence that nitric oxide (NO) and nitric oxide synthase are involved in the development of hyperalgesia in acute inflammatory pain states. The mechanisms responsible for hyperalgesia in chronic pain state may involve not only NO itself, but-also peroxynitrite, the product of its reaction with superoxide radical, ^.O₂^- that can lead to the formation of the free radicals ^.OH and NO₂. Under normal metabolic conditions, the cellular enzyme super oxide dismutase (SOD) provides physiological defence against superoxide radicals. TEMPOL mimics SOD and acts as a catalyst to remove the ^.O₂^- radical. The present work shows the efficacy of a stable nitroxide radical, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), against heat-evoked hyperalgesia.