Anti-nociceptive effect of kinin B-1 and B-2 receptor antagonists on peripheral neuropathy induced by paclitaxel in mice

Anti-nociceptive effect of kinin B-1 and B-2 receptor antagonists on peripheral neuropathy induced by paclitaxel in mice

Author Costa, Robson Google Scholar
Motta, Emerson M. Google Scholar
Dutra, Rafael C. Google Scholar
Manjavachi, Marianne N. Google Scholar
Bento, Allisson F. Google Scholar
Malinsky, Fernanda R. Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Calixto, Joao B. Google Scholar
Institution Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Abstract BACKGROUND and PURPOSEIn the current study, we investigated the role of both kinin B-1 and B-2 receptors in peripheral neuropathy induced by the chronic treatment of mice with paclitaxel a widely used chemotherapeutic agent.EXPERIMENTAL APPROACHChemotherapy-evoked hyperalgesia was induced by i.p. injections of paclitaxel (2 mg.kg(-1)) over 5 consecutive days. Mechanical and thermal hyperalgesia were evaluated between 7 and 21 days after the first paclitaxel treatment.KEY RESULTSTreatment with paclitaxel increased both mechanical and thermal hyperalgesia in mice (C57BL/6 and CD1 strains). Kinin receptor deficient mice (B-1, or B-2 receptor knock-out and B1B2 receptor, double knock-out) presented a significant reduction in paclitaxel-induced hypernociceptive responses in comparison to wild-type animals. Treatment of CD1 mice with kinin receptor antagonists (DALBK for B-1 or Hoe 140 for B-2 receptors) significantly inhibited both mechanical and thermal hyperalgesia when tested at 7 and 14 days after the first paclitaxel injection. DALBK and Hoe 140 were also effective against paclitaxel-induced peripheral neuropathy when given intrathecally or i.c.v.. A marked increase in B-1 receptor mRNA was observed in the mouse thalamus, parietal and pre-frontal cortex from 7 days after the first paclitaxel treatment.CONCLUSIONS and IMPLICATIONSKinins acting on both B-1 and B-2 receptors, expressed in spinal and supra-spinal sites, played a crucial role in controlling the hypernociceptive state caused by chronic treatment with paclitaxel.
Keywords neuropathic pain
chemotherapy
paclitaxel
kinin
B-1 receptor
B-2 receptor
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Programa de Apoio aos Nucleos de Excelencia (PRONEX)
Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
Date 2011-09-01
Published in British Journal of Pharmacology. Hoboken: Wiley-Blackwell, v. 164, n. 2B, p. 681-693, 2011.
ISSN 0007-1188 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 681-693
Origin http://dx.doi.org/10.1111/j.1476-5381.2011.01408.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000294367700024
URI http://repositorio.unifesp.br/handle/11600/33981

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