Barnes Robert C, Banjara Satish, Oliver Ava G, Coulter Margaret, Alanis America, Castro-Piedras Isabel, Ponomarev Igor, Javed Saba, Almodovar Sharilyn, Guindon Josée
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
Eur J Pain. 2025 Jul;29(6):e70066. doi: 10.1002/ejp.70066.
Breast cancer represents the most common cancer diagnosis and the leading cause of cancer-related death in women. Cancer is also associated with pain and changes in both tactile and temperature sensitivity that impair quality of life. While previous studies have investigated the effects of various chemotherapies in murine models of these symptoms, few have previously assessed the effects of cancer alone on these symptoms.
We evaluated the efficacy of murine AT-3 and E0771 breast cancer cell lines on the rate of tumour growth using the Von Frey test (mechanical sensitivity/allodynia) and the acetone test (cold sensitivity/allodynia) in female C57BL/6J wild-type mice. Evaluations for changes in oestrous cycle and mRNA expression in both tumour and whole brain tissue were then performed.
While both cancer cell lines induced significant tumour growth, this growth was significantly greater in the AT-3 cell line than in the E0771 cell line. The AT-3 cell line significantly decreased mechanical and cold sensitivity (allodynia) and significantly altered the oestrous cycle to increase the time spent in a low oestrogen phase (oestrus). In comparison, the E0771 cell line significantly decreased mechanical and cold sensitivity (allodynia) without oestrous cycle alterations. When comparing gene expression in tumour tissue between the two cell lines, the E0771 cell line significantly increased expression of fatty acid amide hydrolase and calcitonin receptor-like.
These results demonstrate the significant impacts of breast cancer on mechanical and cold sensitivity and support the need for further investigations into possible interactions between cancer and chemotherapy in these modalities.
Cancer-associated pain and altered sensations significantly decrease patient quality of life. In our murine model, we have shown that breast cancer cell lines (AT-3 and E0771) alter mechanical and cold sensitivity. These changes coincided with oestrous cycle changes (AT-3) and mRNA expression changes (E0771). A better understanding of our findings will elucidate different mechanisms of action while identifying preventative strategies and potential interactions with chemotherapy.
乳腺癌是女性中最常见的癌症诊断类型，也是癌症相关死亡的主要原因。癌症还与疼痛以及触觉和温度敏感性的变化相关，这些都会损害生活质量。虽然先前的研究已经在这些症状的小鼠模型中研究了各种化疗的效果，但很少有研究评估单独癌症对这些症状的影响。
我们使用Von Frey试验（机械敏感性/异常性疼痛）和丙酮试验（冷敏感性/异常性疼痛）评估了小鼠AT-3和E0771乳腺癌细胞系对雌性C57BL/6J野生型小鼠肿瘤生长速率的影响。然后对发情周期的变化以及肿瘤和全脑组织中的mRNA表达进行了评估。
虽然两种癌细胞系均诱导了显著的肿瘤生长，但AT-3细胞系中的肿瘤生长明显大于E0771细胞系。AT-3细胞系显著降低了机械和冷敏感性（异常性疼痛），并显著改变了发情周期，增加了处于低雌激素阶段（发情期）的时间。相比之下，E0771细胞系显著降低了机械和冷敏感性（异常性疼痛），但没有改变发情周期。在比较两种细胞系肿瘤组织中的基因表达时，E0771细胞系显著增加了脂肪酸酰胺水解酶和降钙素受体样蛋白的表达。
这些结果证明了乳腺癌对机械和冷敏感性有显著影响，并支持进一步研究癌症与化疗在这些方面可能存在的相互作用的必要性。
癌症相关疼痛和感觉改变显著降低患者生活质量。在我们的小鼠模型中，我们已经表明乳腺癌细胞系（AT-3和E0771）会改变机械和冷敏感性。这些变化与发情周期变化（AT-3）和mRNA表达变化（E0771）同时发生。更好地理解我们的发现将阐明不同的作用机制，同时确定预防策略以及与化疗的潜在相互作用。
