title: Anti-nociceptive effect of kinin B₁ and B₂ receptor antagonists on peripheral neuropathy induced by paclitaxel in mice.
abstract: OBJECTIVE
  In the current study, we investigated the role of both kinin B₁ and B₂ receptors in peripheral neuropathy induced by the chronic treatment of mice with paclitaxel a widely used chemotherapeutic agent.
  
  
  METHODS
  Chemotherapy-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.
  
  
  RESULTS
  Treatment with paclitaxel increased both mechanical and thermal hyperalgesia in mice (C57BL/6 and CD1 strains). Kinin receptor deficient mice (B₁, or B₂ 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 B₁ or Hoe 140 for B₂ 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 B₁ receptor mRNA was observed in the mouse thalamus, parietal and pre-frontal cortex from 7 days after the first paclitaxel treatment.
  
  
  CONCLUSIONS
  Kinins acting on both B₁ and B₂ receptors, expressed in spinal and supra-spinal sites, played a crucial role in controlling the hypernociceptive state caused by chronic treatment with paclitaxel.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Costa
authors.forename: Emerson M
authors.initials: EM
authors.lastname: Motta
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Dutra
authors.forename: Marianne N
authors.initials: MN
authors.lastname: Manjavachi
authors.forename: Allisson F
authors.initials: AF
authors.lastname: Bento
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Malinsky
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017239:Paclitaxel / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000700:Analgesics; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D007705:Kinins; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D017239:Paclitaxel; D001920:Bradykinin