Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, United States of America.
PLoS One. 2024 Aug 29;19(8):e0309398. doi: 10.1371/journal.pone.0309398. eCollection 2024.
For many cancer patients tumor burden negatively impacts quality of life due to associated pain onset. Neuropathic pain is commonly associated with late cancer stages, and is resultant of tumor metastasis to bone, herein referred to as cancer-induced bone pain. Given the severe impact on quality of life and clinical treatment strategies focusing on symptom management, novel therapeutics are needed to alleviate cancer-induced bone pain and/or reduce cancer burden. In the current study we characterized a commercially available murine fibrosarcoma cell line, NCTC-2472 in vitro, which can be used to assess the capacity of novel compounds to impact cellular viability. We found that dimethyl sulfoxide, a known cytotoxic agent and common drug preparation compound, significantly decreased cell viability in a dose-related manner. We then characterized the in vivo tumor development and associated pain behavior characteristics following implantation of NCTC-2472 fibrosarcoma into male and female C3H/HeJ mice. The C3H/HeJ strain was utilized as these mice are syngeneic with NCTC-2472 fibrosarcoma and their use reduces potential implantation failure. We found that tumor development in mice resulted in the development of mechanical allodynia but not thermal hyperalgesia. Gabapentin, a clinically relevant analgesic, produced dose-related mechanical allodynia reversal. These studies provide further characterization of a cancer-induced bone pain model that can be used to examine novel compounds as anti-cancer and analgesic therapeutics.
对于许多癌症患者来说,肿瘤负担会导致疼痛的发生,从而对生活质量产生负面影响。神经病理性疼痛通常与晚期癌症阶段有关,是肿瘤转移到骨骼的结果,在此称为癌性骨痛。鉴于对生活质量的严重影响和专注于症状管理的临床治疗策略,需要新型治疗方法来缓解癌性骨痛和/或减轻癌症负担。在本研究中,我们对一种商业上可获得的鼠纤维肉瘤细胞系 NCTC-2472 进行了体外研究,可用于评估新型化合物对细胞活力的影响。我们发现二甲基亚砜,一种已知的细胞毒性剂和常见的药物制备化合物,以剂量相关的方式显著降低细胞活力。然后,我们描述了 NCTC-2472 纤维肉瘤植入雄性和雌性 C3H/HeJ 小鼠后体内肿瘤发展和相关疼痛行为特征。选择 C3H/HeJ 品系是因为这些小鼠与 NCTC-2472 纤维肉瘤同系,并且它们的使用减少了潜在的植入失败。我们发现,小鼠的肿瘤发展导致机械性痛觉过敏的发展,但不导致热痛觉过敏。加巴喷丁,一种临床相关的镇痛药,产生剂量相关的机械性痛觉过敏逆转。这些研究进一步描述了一种癌性骨痛模型,可用于研究新型化合物作为抗癌和镇痛治疗方法。