The kinin B1 and B2 receptors and TNFR1/p55 axis on neuropathic pain in the mouse brachial plexus

  • Nara L. M. QuintãoEmail author
  • Lilian W. Rocha
  • Gislaine F. da Silva
  • Ana F. Paszcuk
  • Marianne N. Manjavachi
  • Allisson F. Bento
  • Kathryn Ana B. S. da Silva
  • Maria M. Campos
  • João B. Calixto
Original Article


Tumour necrosis factor (TNF) and kinins have been associated with neuropathic pain-like behaviour in numerous animal models. However, the way that they interact to cause neuron sensitisation remains unclear. This study assessed the interaction of kinin receptors and TNF receptor TNFR1/p55 in mechanical hypersensitivity induced by an intraneural (i.n.) injection of rm-TNF into the lower trunk of brachial plexus in mice. The i.n. injection of rm-TNF reduced the mechanical withdrawal threshold of the right forepaw from the 3rd to the 10th day after the injection, indicating that TNF1/p55 displays a critical role in the onset of TNF-elicited neuropathic pain. The connection between TNF1/p55 and kinin B1 and B2 receptors (B1R and B2R) was confirmed using both knockout mice and mRNAs quantification in the injected nerve, DRG and spinal cord. The treatment with the B2R antagonist HOE 140 or with B1R antagonist des-Arg9-Leu8-BK reduced both BK- and DABK-induced hypersensitivity. The experiments using kinin receptor antagonists and CPM inhibitor (thiorphan) suggest that BK does not only activate B2R as an orthosteric agonist, but also seems to be converted into DABK that consequently activates B1R. These results indicate a connection between TNF and the kinin system, suggesting a relevant role for B1R and B2R in the process of sensitisation of the central nervous systems by the cross talk between the receptor and CPM after i.n. injection of rm-TNF.


Brachial plexus Cytokine TNF Neuropathic pain Kinin receptors Carboxypeptidase 



This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Fundação de Apoio a Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC), and the Programa de Apoio aos Núcleos de Excelência (PRONEX), Brazil. A. F. P., M. N. M., and A. F. B. were Ph.D. students supported by grants from CNPq and CAPES (Financial Code 001). We are grateful to C. Scheidt for his help in the conception of Figs. 7 and 8 illustrations.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nara L. M. Quintão
    • 1
    Email author
  • Lilian W. Rocha
    • 1
  • Gislaine F. da Silva
    • 1
  • Ana F. Paszcuk
    • 2
  • Marianne N. Manjavachi
    • 2
  • Allisson F. Bento
    • 2
  • Kathryn Ana B. S. da Silva
    • 1
  • Maria M. Campos
    • 3
  • João B. Calixto
    • 2
    • 4
  1. 1.Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da SaúdeUniversidade do Vale do ItajaíItajaíBrazil
  2. 2.Departamento de Farmacologia, Centro de Ciências BiológicasUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  3. 3.Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da SaúdePontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  4. 4.Centro de Inovação e Ensaios pré-clínicosFlorianópolisBrazil

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