Hyperalgesia due to nerve injury - Role of peroxynitrite

We carried out a partial ligation of the sciatic nerve in rats to induce ne rve injury and neuropathic hyperalgesia. We showed that nitrotyrosine, a ma rker of peroxynitrite activity, was formed after partial nerve injury. Doub le-labelling immunohistochemistry showed that nitrotyrosine-immunoreactive cells were mainly macrophages and Schwann cells. Daily treatment with uric acid, a scavenger of peroxynitrite, decreased nitrotyrosine formation in th e injured sciatic nerve, and produced concomitant alleviation of thermal hy peralgesia and Wallerian degeneration. These results provide the first evidence that peroxynitrite is formed after partial nerve injury, and contributes to the initiation of thermal hyperal gesia and Wallerian degeneration. We hypothesize that uric acid alleviates hyperalgesia and Wallerian degeneration by inhibiting oxidative damage caus ed by peroxynitrite and possibly also by decreasing the production of other inflammatory mediators such as prostaglandins. (C) 2000 IBRO. Published by Elsevier Science Ltd.