肿瘤或芳香化酶抑制剂（AIs）引起的疼痛是乳腺癌幸存者的一种致残症状。它们的机制不清楚，但与促痛和炎症介质有关。肽酶是内源性疼痛介质，通过B1和B2受体激活与多种疼痛情况相关，包括化疗引起的疼痛和乳腺癌增殖。我们研究了肽酶B1和B2受体在转移性乳腺肿瘤（4T1乳腺癌细胞）引起的疼痛和芳香化酶抑制剂（阿那曲唑或来曲唑）治疗相关疼痛中的作用。还进行了肿瘤和抗肿瘤治疗联合实验。通过药理拮抗、受体蛋白表达和肽酶水平等方法，研究了肽酶受体的作用。评估了机械和冷感觉觉过敏以及肌肉力量。AIs和乳腺肿瘤增加了肽酶受体的表达，肿瘤还增加了肽酶水平。AIs引起了小鼠的机械感觉过敏和肌肉力量减弱。肽酶B1（DALBk）和B2（Icatibant）受体拮抗剂减轻了这些影响，并减少了乳腺肿瘤引起的机械和冷感觉过敏。AIs或紫杉醇增强了乳腺肿瘤引起的机械过敏，而DALBk和Icatibant受体拮抗剂防止了这种增加。受体拮抗剂未干扰紫杉醇的体外细胞毒作用。因此，肽酶B1或B2受体可以成为治疗转移性乳腺肿瘤及其抗肿瘤治疗引起的疼痛的潜在靶点。©2023年作者。

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.© 2023. The Author(s).