Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis.
We investigated the contribution of neutrophils to joint hyperalgesia and peroxynitrite formation in zymosan arthritis. Rats received 1 mg zymosan intra-articular, and joint hyperalgesia was measured using the rat knee-joint articular incapacitation test. After 6 h, joint exudates were collected by aspiration for the assessment of cell influx, myeloperoxidase activity, and nitrite (as an index of nitric oxide formation) levels. Nitrotyrosine content, used as an index of peroxynitrite formation, was measured in joint exudates, using enzyme-linked immunosorbent assay. A group of rats was rendered neutropenic through the administration of a rabbit anti-rat neutrophil antibody (2 ml kg(-1), i.p.) 30 min before injection of 1 mg zymosan intra-articular. Other groups received uric acid (100 or 250 mg kg(-1), i.p.), the peroxynitrite scavenger, 30 min before 1 mg zymosan intra-articular. Controls received the vehicle. The significant inhibition of joint hyperalgesia in neutropenic animals was associated to significantly decreased cell influx, myeloperoxidase activity, nitric oxide, and nitrotyrosine levels in the joint exudates, as compared to naive rats. Uric acid administration inhibited both hyperalgesia and cell influx, as compared to controls. Neutrophils are involved in both nitric oxide and peroxynitrite formation in zymosan arthritis, thereby contributing to acute joint hyperalgesia. Scavenging of reactive nitrogen species (e.g. peroxynitrite) inhibits neutrophil migration and joint hyperalgesia in the acute phase of zymosan arthritis in rats.
Bezerra
Mirna M
MM
Department of Physiology and Pharmacology, Faculty of Medicine of Sobral, Federal University of Ceará, Rua Geraldo Rangel, s/n, Derby, Sobral, Ceará, Brazil.
Brain
Susan D
SD
Girão
Virgínia C C
VC
Greenacre
Stan
S
Keeble
Julie
J
Rocha
Francisco A C
FA
D000208:Acute Disease; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D006614:Hindlimb / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000097:blood / Q000378:metabolism*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014527:Uric Acid / Q000008:administration & dosage / Q000097:blood; D015054:Zymosan / Q000008:administration & dosage / Q000633:toxicity*
D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D014527:Uric Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D015054:Zymosan; D009195:Peroxidase