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

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An Erratum to this article was published on 29 January 2013

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.

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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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Author notes

  1. Waldiceu A. Verri Jr. & Thiago M. Cunha

    Present address: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Avenida Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Avenida Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil

    Ana T. Guerrero, Silvio M. Vieira, Larissa G. Pinto, Sérgio H. Ferreira & Fernando Q. Cunha

  2. Fundação Oswaldo Cruz (FIOCRUZ), Mato Grosso do Sul, Gabriel Abrão, 90, Campo Grande, Brazil

    Ana T. Guerrero

  3. Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Paraná, Rod. Celso Garcia Cid KM380 PR445, 86051-990, Londrina, Paraná, Brazil

    Ana C. Zaperlon & Waldiceu A. Verri Jr.

  4. Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrinal, Paraná, Rod. Celso Garcia Cid KM380 PR445, 86051-990, Londrina, Paraná, Brazil

    Silvio M. Vieira

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Correspondence to Waldiceu A. Verri Jr. or Thiago M. Cunha.

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A.T. Guerrero and A.C. Zaperlon contributed equally to this work.

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Guerrero, A.T., Zaperlon, A.C., Vieira, S.M. et al. The role of PAF/PAFR signaling in zymosan-induced articular inflammatory hyperalgesia. Naunyn-Schmiedeberg's Arch Pharmacol 386, 51–59 (2013). https://doi.org/10.1007/s00210-012-0813-4

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