Hyperalgesia due to nerve injury-role of peroxynitrite.
We carried out a partial ligation of the sciatic nerve in rats to induce nerve injury and neuropathic hyperalgesia. We showed that nitrotyrosine, a marker of peroxynitrite activity, was formed after partial nerve injury. Double-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 the injured sciatic nerve, and produced concomitant alleviation of thermal hyperalgesia and Wallerian degeneration. These results provide the first evidence that peroxynitrite is formed after partial nerve injury, and contributes to the initiation of thermal hyperalgesia and Wallerian degeneration. We hypothesize that uric acid alleviates hyperalgesia and Wallerian degeneration by inhibiting oxidative damage caused by peroxynitrite and possibly also by decreasing the production of other inflammatory mediators such as prostaglandins.
Liu
T
T
School of Anatomy, University of New South Wales, Sydney, Australia.
Knight
K R
KR
Tracey
D J
DJ
D000818:Animals; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D009408:Nerve Compression Syndromes / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009409:Nerve Crush / Q000009:adverse effects*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009437:Neuralgia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009566:Nitrates / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology
D009566:Nitrates; C039642:peroxynitric acid; D014527:Uric Acid; C002744:3-nitrotyrosine; D014443:Tyrosine