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首页> 外文期刊>Life sciences >A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss.
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A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss.

机译：大麻素2受体激动剂可减轻骨癌引起的疼痛和骨质流失。

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AIMS: Cannabinoid CB(2) agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB(2) agonist, does not demonstrate central nervous system side effects seen with CB(1) agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB(2) selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB(2) agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. MAIN METHODS: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. KEY FINDINGS: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. SIGNIFICANCE: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.
机译：目的：大麻素CB（2）激动剂已显示出减轻动物模型中炎症性和神经性疼痛的行为迹象。 C124（2）激动剂AM1241并未表现出CB（1）激动剂（如体温过低和僵直）所见的中枢神经系统副作用。转移性骨癌会给患者带来严重的疼痛，并需使用止痛药（如鸦片）进行治疗。最近的报道表明，在鸦片骨癌小鼠模型中，持续的鸦片制剂可产生矛盾的痛觉过敏作用并增强骨破坏。相反，已证明CB（2）选择性激动剂可减少与骨质疏松症模型相关的骨质流失。在这里，我们测试了在7天的时间内服用的CB（2）激动剂是否能抑制骨癌引起的疼痛并减轻癌症引起的骨降解。主要方法：使用鼠骨癌模型，将溶骨肉瘤细胞注入股骨远端的髓内腔。在将肿瘤细胞注入股骨后的第7、10和14天进行行为和射线照相图像分析。主要发现：股骨内的溶骨肉瘤在荷瘤的四肢内产生了自发的，触动的疼痛行为迹象。急性或连续7天全身性使用AM1241可以显着减轻接种肢体的自发性和诱发性疼痛。持续的AM1241可以显着减少骨质流失并降低癌症引起的骨折的发生率。意义：这些发现表明，一种针对癌症引起的骨痛，骨质流失和骨折的新型疗法，同时缺乏目前针对骨癌痛的疗法所见的许多不良副作用。

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