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Papers of the Week

Papers: 18 Mar 2023 - 24 Mar 2023

Basic Science

Animal Studies, Neurobiology, Pharmacology/Drug Development

Cancer Pain

2023 Mar 17

Sci Rep




Kinin B and B receptors mediate cancer pain associated with both the tumor and oncology therapy using aromatase inhibitors.


Brusco I, Becker G, Palma TV, Pillat MM, Scussel R, Steiner BT, Sampaio TB, Ardisson-Araújo DMP, de Andrade CM, Oliveira MS, Machado-De-Avila RA, Oliveira SM


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