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However, patients who receive even a single dose with PCX commonly develop mechanical and cold allodynia, a symptom known as PCX\u2010associated acute pain syndrome (P\u2010APS). Here, we assessed possible involvement of kinin\u2013kallikrein and renin\u2010angiotensin systems in P\u2010APS in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male mice C57Bl\/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1<jats:sup>\u2212\/\u2212<\/jats:sup>) and B2 (B2<jats:sup>\u2212\/\u2212<\/jats:sup>), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P\u2010APS was induced by administration of PCX 4\u00a0mg\/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\u2010PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of PCX in B1<jats:sup>\u2212\/\u2212<\/jats:sup> and B2<jats:sup>\u2212\/\u2212<\/jats:sup> mice induced lower mechanical and cold allodynia compared to the WT. However, the pre\u2010treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P\u2010APS. Surprisingly, we found that mice pre\u2010treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P\u2010APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P\u2010APS in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Kinin\u2013kallikrein and renin\u2010angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel\u2010associated acute pain syndrome (P\u2010APS) in mice. Antagonists for AT2R are potential alternatives to prevent P\u2010APS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1660","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:53:26Z","timestamp":1600854806000},"page":"189-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel\u2010associated acute pain syndrome in mice"],"prefix":"10.1002","volume":"25","author":[{"given":"Graziele C.","family":"Zanata","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School University of S\u00e3o Paulo Ribeirao Preto Brazil"},{"name":"Bar\u00e3o de Maua University Center Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa G.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School University of S\u00e3o Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre H. 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