Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, United States.
Life Sci. 2010 Apr 24;86(17-18):646-53. doi: 10.1016/j.lfs.2010.02.014. Epub 2010 Feb 20.
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.
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.
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.
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.
大麻素 CB(2) 受体激动剂已被证明可减轻动物模型中炎症和神经病理性疼痛的行为症状。AM1241 是一种 CB(2) 受体激动剂，不会表现出与 CB(1) 受体激动剂（如体温过低和僵住）相关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，并采用阿片类药物等镇痛药进行治疗。最近的报告表明，持续使用阿片类药物会产生矛盾的痛觉过敏作用，并增强骨癌小鼠模型中的骨破坏。相比之下，CB(2) 选择性激动剂已被证明可减少与骨质疏松症模型相关的骨丢失。在这里，我们测试了在 7 天内给予 CB(2) 激动剂是否可以抑制骨癌引起的疼痛，并减轻癌症引起的骨降解。
使用鼠骨癌模型，将溶骨性肉瘤细胞注入股骨远端骨髓腔内。在肿瘤细胞注入股骨后第 7、10 和 14 天进行行为和放射图像分析。
股骨内的溶骨性肉瘤会在肿瘤受累肢体中自发产生触摸诱发的疼痛行为迹象。AM1241 的全身给药急性或持续 7 天可显著减轻接种肢体的自发性和诱发性疼痛。持续给予 AM1241 可显著减少骨丢失并降低癌症引起的骨折发生率。
这些发现为癌症引起的骨痛、骨丢失和骨折提供了一种新的治疗方法，同时缺乏当前治疗骨癌疼痛的许多不良副作用。
