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

• Autor(a) principal: Costa, Robson
• Data de Publicação: 2011
• Outros Autores: Motta, Emerson M., Dutra, Rafael C., Manjavachi, Marianne N., Bento, Allisson F., Malinsky, Fernanda R. [UNIFESP], Pesquero, João Bosco [UNIFESP], Calixto, Joao B.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1111/j.1476-5381.2011.01408.x; http://repositorio.unifesp.br/handle/11600/33981
• topic: neuropathic pain; chemotherapy; paclitaxel; kinin; B-1 receptor; B-2 receptor

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.