التفاصيل البيبلوغرافية
| العنوان: |
Anti-nociceptive effect of kinin B₁ and B₂ receptor antagonists on peripheral neuropathy induced by paclitaxel in mice. |
| المؤلفون: |
Costa, Robson, Motta, Emerson M, Dutra, Rafael C, Manjavachi, Marianne N, Bento, Allisson F, Malinsky, Fernanda R, Pesquero, João B, Calixto, João B, Pesquero, João B, Calixto, João B |
| المصدر: |
British Journal of Pharmacology; Sep2011, Vol. 164 Issue 2b, p681-693, 13p |
| مصطلحات موضوعية: |
KININS, HORMONE antagonists, NEUROPATHY, PACLITAXEL, SPINAL injections, DRUG therapy, HYPERALGESIA, LABORATORY mice, RESEARCH, PERIPHERAL neuropathy, ANTI-inflammatory agents, ANALGESICS, ANIMAL experimentation, RESEARCH methodology, HEMATOLOGIC agents, CELL receptors, RNA, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, VASODILATORS, INFLAMMATORY mediators, MICE, PHARMACODYNAMICS |
| مستخلص: |
Background and Purpose: 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.Experimental Approach: 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.Key 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 and Implications: 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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