Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 374, Issue 4, pp 265–273 | Cite as

Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis

  • Mirna M. Bezerra
  • Susan D. Brain
  • Virgínia C. C. Girão
  • Stan Greenacre
  • Julie Keeble
  • Francisco A. C. Rocha
Original Article

Abstract

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.

Keywords

Inflammation Peroxynitrite Neutrophils Zymosan Uric Acid 

Abbreviations

DMARDS

disease modifying anti-rheumatic drugs

i.art

intra-articular

L-NAME

N-nitro-l-arginine methyl ester

LTB4

leukotriene B4

MPO

myeloperoxidase

NO

nitric oxide

NOS

nitric oxide synthase

NT

non-treated

PET

paw elevation time

PN

peroxynitrite

RA

rheumatoid arthritis

SIN-1

3-Morpholinosydnonimine

SOD

superoxide dismutase

TMB

tetramethylbenzene

Notes

Acknowledgement

The authors thank Fundação Cearense de Desenvolvimento Científico e Tecnológico (FUNCAP) and CNPq, Brazil.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Mirna M. Bezerra
    • 1
  • Susan D. Brain
    • 2
  • Virgínia C. C. Girão
    • 1
  • Stan Greenacre
    • 2
  • Julie Keeble
    • 2
  • Francisco A. C. Rocha
    • 3
    • 4
  1. 1.Department of Physiology and Pharmacology, Faculty of Medicine of SobralFederal University of CearáSobralBrazil
  2. 2.Centre for Cardiovascular Biology and Medicine, New Hunt’s HouseKing’s College LondonLondonUK
  3. 3.Department of Internal MedicineFederal University of CearáFortalezaBrazil
  4. 4.Faculty of MedicineFederal University of CearáFortalezaBrazil

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