Abstract

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 B1 and B2 receptor activation, including chemotherapy-induced pain and breast cancer proliferation. We investigate the involvement of the kinin B1 and B2 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 B1 (DALBk) and B2 (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 B1 or B2 receptors can be a potential target for treating the pain caused by metastatic breast tumor and their antineoplastic therapy.

Details

Title
Kinin B1 and B2 receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors
Author
Brusco, Indiara 1 ; Becker, Gabriela 1 ; Palma, Tais Vidal 1 ; Pillat, Micheli Mainardi 2 ; Scussel, Rahisa 3 ; Steiner, Bethina Trevisol 3 ; Sampaio, Tuane Bazanella 4 ; Ardisson-Araújo, Daniel Mendes Pereira 5 ; de Andrade, Cinthia Melazzo 1 ; Oliveira, Mauro Schneider 4 ; Machado-De-Avila, Ricardo Andrez 3 ; Oliveira, Sara Marchesan 1   VIAFID ORCID Logo 

 Federal University of Santa Maria, Graduate Program in Biological Sciences: Biochemistry Toxicology, Department of Biochemistry and Molecular Biology, Santa Maria, Brazil (GRID:grid.411239.c) (ISNI:0000 0001 2284 6531) 
 Federal University of Santa Maria, Department of Microbiology and Parasitology, Santa Maria, Brazil (GRID:grid.411239.c) (ISNI:0000 0001 2284 6531) 
 University of Extreme South Catarinense, Graduate Program in Health Sciences, Criciuma, Brazil (GRID:grid.411239.c) 
 Federal University of Santa Maria, Graduate Program in Pharmacology, Department of Physiology and Pharmacology, Santa Maria, Brazil (GRID:grid.411239.c) (ISNI:0000 0001 2284 6531) 
 Federal University of Santa Maria, Graduate Program in Biological Sciences: Biochemistry Toxicology, Department of Biochemistry and Molecular Biology, Santa Maria, Brazil (GRID:grid.411239.c) (ISNI:0000 0001 2284 6531); University of Brasilia, Department of Cell Biology, Institute of Biological Sciences, Brasilia, Brazil (GRID:grid.7632.0) (ISNI:0000 0001 2238 5157) 
Pages
4418
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2787763867
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.