Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil.
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), 97105-900 Santa Maria, RS, Brazil.
Life Sci. 2021 Jul 1;276:119469. doi: 10.1016/j.lfs.2021.119469. Epub 2021 Mar 31.
Breast cancer-induced chronic pain is usually treated with opioids, but these compounds cause various adverse effects. Transient receptor potential ankyrin 1 (TRPA1) is involved in cancer pain; also, endogenous TRPA1 agonists are associated with cancer pain development. The aim of this study was to observe the antinociceptive effect of a repeated-dose TRPA1 antagonist administration and the production of endogenous TRPA1 agonists and TRPA1 expression in bone tissue in a model of breast cancer pain in mice. Second, we used a sequence reading archive (SRA) strategy to observe the presence of this channel in the mouse bone and in mouse bone cell lines.
We used BALB/c mice for experiments. The animals were subjected to the tumor cell inoculation (4 T1 strain). HC-030031 (a TRPA1 antagonist) treatment was done from day 11 to day 20 after tumor inoculation. TRPA1 expression and biochemical tests of oxidative stress were performed in the bone of mice (femur). SRA strategy was used to detect the TRPA1 presence.
Repeated treatment with the TRPA1 antagonist produced an antinociceptive effect. There was an increase in hydrogen peroxide levels, NADPH oxidase and superoxide dismutase activities, but the expression of TRPA1 in the bone tissue was not altered. SRA did not show TRPA1 residual transcription in the osteoblast and osteoclast cell lines, as well as for mice cranial tissue and in mouse osteoclast precursors.
The TRPA1 receptor is a potential target for the development of new painkillers for the treatment of bone cancer pain.
乳腺癌引起的慢性疼痛通常采用阿片类药物治疗，但这些化合物会引起各种不良反应。瞬时受体电位锚蛋白 1（TRPA1）参与癌症疼痛；此外，内源性 TRPA1 激动剂与癌症疼痛的发展有关。本研究旨在观察重复给予 TRPA1 拮抗剂对乳腺癌疼痛模型中小鼠骨组织中内源性 TRPA1 激动剂的产生和 TRPA1 表达的镇痛作用。其次，我们使用序列读取档案（SRA）策略来观察该通道在小鼠骨组织和小鼠骨细胞系中的存在。
我们使用 BALB/c 小鼠进行实验。动物接受肿瘤细胞接种（4T1 株）。在肿瘤接种后第 11 天至第 20 天给予 HC-030031（TRPA1 拮抗剂）治疗。对小鼠（股骨）骨中的 TRPA1 表达和氧化应激生化检测进行检测。使用 SRA 策略检测 TRPA1 的存在。
重复给予 TRPA1 拮抗剂可产生镇痛作用。过氧化氢水平、NADPH 氧化酶和超氧化物歧化酶活性增加，但骨组织中 TRPA1 的表达未改变。SRA 未显示成骨细胞和破骨细胞系、小鼠颅组织以及小鼠破骨细胞前体中 TRPA1 的残留转录。
TRPA1 受体是开发新的骨癌疼痛治疗止痛药的潜在靶点。
