Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel‐associated acute pain syndrome in mice
| Autor: | Graziele C Zanata, Francisco Fábio Bezerra de Oliveira, Rangel L. Silva, Larissa G. Pinto, Alexandre H. Lopes, Peter A. McNaughton, Nicole Rodrigues da Silva, Fernando Q. Cunha, Thiago M. Cunha, Ieda Regina dos Santos Schivo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Paclitaxel Bradykinin Angiotensin II Type 2 Receptor Blockers Pharmacology Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals EMA401 030212 general & internal medicine Enalapril Receptor Bradykinin Receptor Antagonists Mice Knockout business.industry Receptors Bradykinin Captopril Acute Pain Angiotensin II Mice Inbred C57BL GENÉTICA Anesthesiology and Pain Medicine Allodynia Losartan chemistry medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Background Paclitaxel (PCX) is the first-line choice for the treatment of several types of cancer, including breast, ovarian, and lung cancers. However, patients who receive even a single dose with PCX commonly develop mechanical and cold allodynia, a symptom known as PCX-associated acute pain syndrome (P-APS). Here, we assessed possible involvement of kinin-kallikrein and renin-angiotensin systems in P-APS in mice. Methods Male mice C57Bl/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1-/- ) and B2 (B2-/- ), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P-APS was induced by administration of PCX 4 mg/kg, i.v.. ACE inhibitors (captopril and enalapril), antagonists for angiotensin II type 1 (losartan) and type 2 ([AT2R]; PD123319 and EMA 401) receptors were administrated prior the treatment with PCX. RT-PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors. Results Administration of PCX in B1-/- and B2-/- mice induced lower mechanical and cold allodynia compared to the WT. However, the pre-treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P-APS. Surprisingly, we found that mice pre-treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX. Conclusion Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P-APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P-APS in humans. Significance Kinin-kallikrein and renin-angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel-associated acute pain syndrome (P-APS) in mice. Antagonists for AT2R are potential alternatives to prevent P-APS. |
| Databáze: | OpenAIRE |
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