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Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors

Pain caused by the tumor or aromatase inhibitors (AIs) is a disabling symptom in breast cancer survivors. Their mechanisms are unclear, but pro-algesic and inflammatory mediators seem to be involved. Kinins are endogenous algogenic mediators associated with various painful conditions via B(1) and B(...

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Autores principales: Brusco, Indiara, Becker, Gabriela, Palma, Tais Vidal, Pillat, Micheli Mainardi, Scussel, Rahisa, Steiner, Bethina Trevisol, Sampaio, Tuane Bazanella, Ardisson-Araújo, Daniel Mendes Pereira, de Andrade, Cinthia Melazzo, Oliveira, Mauro Schneider, Machado-De-Avila, Ricardo Andrez, Oliveira, Sara Marchesan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023805/
https://www.ncbi.nlm.nih.gov/pubmed/36932156
http://dx.doi.org/10.1038/s41598-023-31535-6
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author Brusco, Indiara
Becker, Gabriela
Palma, Tais Vidal
Pillat, Micheli Mainardi
Scussel, Rahisa
Steiner, Bethina Trevisol
Sampaio, Tuane Bazanella
Ardisson-Araújo, Daniel Mendes Pereira
de Andrade, Cinthia Melazzo
Oliveira, Mauro Schneider
Machado-De-Avila, Ricardo Andrez
Oliveira, Sara Marchesan
author_facet Brusco, Indiara
Becker, Gabriela
Palma, Tais Vidal
Pillat, Micheli Mainardi
Scussel, Rahisa
Steiner, Bethina Trevisol
Sampaio, Tuane Bazanella
Ardisson-Araújo, Daniel Mendes Pereira
de Andrade, Cinthia Melazzo
Oliveira, Mauro Schneider
Machado-De-Avila, Ricardo Andrez
Oliveira, Sara Marchesan
author_sort Brusco, Indiara
collection PubMed
description Pain caused by the tumor or aromatase inhibitors (AIs) is a disabling symptom in breast cancer survivors. Their mechanisms are unclear, but pro-algesic and inflammatory mediators seem to be involved. Kinins are endogenous algogenic mediators associated with various painful conditions via B(1) and B(2) receptor activation, including chemotherapy-induced pain and breast cancer proliferation. We investigate the involvement of the kinin B(1) and B(2) receptors in metastatic breast tumor (4T1 breast cancer cells)-caused pain and in aromatase inhibitors (anastrozole or letrozole) therapy-associated pain. A protocol associating the tumor and antineoplastic therapy was also performed. Kinin receptors’ role was investigated via pharmacological antagonism, receptors protein expression, and kinin levels. Mechanical and cold allodynia and muscle strength were evaluated. AIs and breast tumor increased kinin receptors expression, and tumor also increased kinin levels. AIs caused mechanical allodynia and reduced the muscle strength of mice. Kinin B(1) (DALBk) and B(2) (Icatibant) receptor antagonists attenuated these effects and reduced breast tumor-induced mechanical and cold allodynia. AIs or paclitaxel enhanced breast tumor-induced mechanical hypersensitivity, while DALBk and Icatibant prevented this increase. Antagonists did not interfere with paclitaxel's cytotoxic action in vitro. Thus, kinin B(1) or B(2) receptors can be a potential target for treating the pain caused by metastatic breast tumor and their antineoplastic therapy.
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spelling pubmed-100238052023-03-19 Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors Brusco, Indiara Becker, Gabriela Palma, Tais Vidal Pillat, Micheli Mainardi Scussel, Rahisa Steiner, Bethina Trevisol Sampaio, Tuane Bazanella Ardisson-Araújo, Daniel Mendes Pereira de Andrade, Cinthia Melazzo Oliveira, Mauro Schneider Machado-De-Avila, Ricardo Andrez Oliveira, Sara Marchesan Sci Rep Article Pain caused by the tumor or aromatase inhibitors (AIs) is a disabling symptom in breast cancer survivors. Their mechanisms are unclear, but pro-algesic and inflammatory mediators seem to be involved. Kinins are endogenous algogenic mediators associated with various painful conditions via B(1) and B(2) receptor activation, including chemotherapy-induced pain and breast cancer proliferation. We investigate the involvement of the kinin B(1) and B(2) receptors in metastatic breast tumor (4T1 breast cancer cells)-caused pain and in aromatase inhibitors (anastrozole or letrozole) therapy-associated pain. A protocol associating the tumor and antineoplastic therapy was also performed. Kinin receptors’ role was investigated via pharmacological antagonism, receptors protein expression, and kinin levels. Mechanical and cold allodynia and muscle strength were evaluated. AIs and breast tumor increased kinin receptors expression, and tumor also increased kinin levels. AIs caused mechanical allodynia and reduced the muscle strength of mice. Kinin B(1) (DALBk) and B(2) (Icatibant) receptor antagonists attenuated these effects and reduced breast tumor-induced mechanical and cold allodynia. AIs or paclitaxel enhanced breast tumor-induced mechanical hypersensitivity, while DALBk and Icatibant prevented this increase. Antagonists did not interfere with paclitaxel's cytotoxic action in vitro. Thus, kinin B(1) or B(2) receptors can be a potential target for treating the pain caused by metastatic breast tumor and their antineoplastic therapy. Nature Publishing Group UK 2023-03-17 /pmc/articles/PMC10023805/ /pubmed/36932156 http://dx.doi.org/10.1038/s41598-023-31535-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Brusco, Indiara
Becker, Gabriela
Palma, Tais Vidal
Pillat, Micheli Mainardi
Scussel, Rahisa
Steiner, Bethina Trevisol
Sampaio, Tuane Bazanella
Ardisson-Araújo, Daniel Mendes Pereira
de Andrade, Cinthia Melazzo
Oliveira, Mauro Schneider
Machado-De-Avila, Ricardo Andrez
Oliveira, Sara Marchesan
Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title_full Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title_fullStr Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title_full_unstemmed Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title_short Kinin B(1) and B(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
title_sort kinin b(1) and b(2) receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023805/
https://www.ncbi.nlm.nih.gov/pubmed/36932156
http://dx.doi.org/10.1038/s41598-023-31535-6
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