Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel-associated acute pain syndrome in mice.

Autor: Zanata GC; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.; Barão de Maua University Center, Ribeirão Preto, Brazil., Pinto LG; Wolfson Centre for Age-Related Diseases, King's College London, London, UK., da Silva NR; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Lopes AHP; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., de Oliveira FFB; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil., Schivo IRS; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Cunha FQ; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., McNaughton P; Wolfson Centre for Age-Related Diseases, King's College London, London, UK., Cunha TM; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Silva RL; Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.; Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
Jazyk: angličtina
Zdroj: European journal of pain (London, England) [Eur J Pain] 2021 Jan; Vol. 25 (1), pp. 189-198. Date of Electronic Publication: 2020 Oct 06.
DOI: 10.1002/ejp.1660
Abstrakt: 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.
(© 2020 European Pain Federation - EFIC®.)
Databáze: MEDLINE
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