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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 1, pp 51–59 | Cite as

The role of PAF/PAFR signaling in zymosan-induced articular inflammatory hyperalgesia

  • Ana T. Guerrero
  • Ana C. Zaperlon
  • Silvio M. Vieira
  • Larissa G. Pinto
  • Sérgio H. Ferreira
  • Fernando Q. Cunha
  • Waldiceu A. VerriJr.Email author
  • Thiago M. CunhaEmail author
Original Article

Abstract

Platelet-activating factor (PAF) and its receptor (PAFR) have been shown to be involved in several inflammatory events, including neutrophil chemoattraction and nociception. The present study addressed the role of PAF in the genesis of articular hyperalgesia in a model of joint inflammation. Zymosan-induced articular hyperalgesia, oedema and neutrophil migration were dose-dependently reduced following pretreatment with selective PAFR antagonists, UK74505 (5, 10 and 20 mg/kg) and PCA4248 (3, 10, 30 mg/kg). These parameters were also reduced in PAF receptor-deficient mice (PAFR−/−). The hyperalgesic action of PAF was further confirmed by the demonstration that joint injection of PAF induces a dose- (0.3, 1 and 3 μg/joint), time- and PAFR-dependent articular hyperalgesia and oedema. The PAF hyperalgesic mechanisms were dependent on prostaglandins, leukotrienes and neutrophils, as PAF-induced articular hyperalgesia was inhibited by indomethacin (COX inhibitor), MK886 (leukotrienes synthesis inhibitor) or fucoidan (leukocyte rolling inhibitor). Furthermore, PAF-induced hyperalgesia was reduced in 5-lypoxigenase-null mice. In corroboration of these findings, intra-articular injection of PAF promotes the production of LTB4 as well as the recruitment of neutrophils to the joint. These results suggest that PAF may participate in the cascade of events involved in the genesis of articular inflammatory hyperalgesia via stimulation of prostaglandins, leukotrienes and neutrophil migration. Finally, targeting PAF action (e.g., with a PAFR antagonist) might provide a useful therapeutic approach to inhibit articular inflammatory hyperalgesia.

Keywords

Zymosan Joint pain Arthritis Hyperalgesia PAF Neutrophils 

Notes

Acknowledgments

This work was supported by grants from Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Pesquisa (CNPq) in Brazil. We thank the excellent technical assistance of Ana K. dos Santos, Giuliana B. Francisco, Ieda Regina dos Santos Schivo and Sérgio R. Rosa.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ana T. Guerrero
    • 1
    • 2
  • Ana C. Zaperlon
    • 3
  • Silvio M. Vieira
    • 1
    • 4
  • Larissa G. Pinto
    • 1
  • Sérgio H. Ferreira
    • 1
  • Fernando Q. Cunha
    • 1
  • Waldiceu A. VerriJr.
    • 1
    • 3
    Email author
  • Thiago M. Cunha
    • 1
    Email author
  1. 1.Department of Pharmacology, School of Medicine of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil
  2. 2.Fundação Oswaldo Cruz (FIOCRUZ), Mato Grosso do SulCampo GrandeBrazil
  3. 3.Departamento de Patologia, Centro de Ciências BiológicasUniversidade Estadual de LondrinaLondrinaBrazil
  4. 4.Departamento de Patologia, Centro de Ciências BiológicasUniversidade Estadual de LondrinalLondrinaBrazil

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