Kato Akira, Minami Kazuhisa, Ito Hisanori, Tomii Takako, Matsumoto Mitsunobu, Orita Satoshi, Kihara Tsuyoshi, Narita Minoru, Suzuki Tsutomu
Pain and Neurology, Discovery Research Laboratories, Shionogi & Co., Ltd., Koka, Japan.
Oncology. 2008;74 Suppl 1:55-60. doi: 10.1159/000143220. Epub 2008 Aug 28.
The femur bone cancer pain model was developed by implanting mouse osteolytic tumor cells (NCTC 2472) into the intramedulla of the femur in C3H/HeN mice. In vivo imaging analysis revealed that the implanted tumor cells grew progressively over 14 days. Associated with the tumor growth, guarding behavior, which was an indication of ongoing pain, time-dependently increased. Limb use abnormality and allodynia, which were indications of ambulatory and neuropathic pain, respectively, also appeared. The analgesic effects of oxycodone and other opioids, such as morphine and fentanyl, were evaluated at 14 days when all pain-related behaviors clearly appeared. Oxycodone (2-20 mg/kg, s.c.), morphine (10-50 mg/kg, s.c.) and fentanyl (0.05-0.2 mg/kg, s.c.) significantly reduced guarding behavior. Oxycodone (5-20 mg/kg, s.c.) and fentanyl (0.1 and 0.2 mg/kg, s.c.) significantly reversed limb use abnormality, but morphine (5-50 mg/kg, s.c.) did not. Moreover, oxycodone (5-20 mg/kg, s.c.) dose-dependently reversed allodynia without affecting the sham-treated mice. Morphine (50 mg/kg, s.c.) and fentanyl (0.075-0.2 mg/kg, s.c.) also reversed allodynia, but morphine (50 mg/kg, s.c.) tended to affect and fentanyl (0.1 and 0.2 mg/kg, s.c.) affected the withdrawal threshold in sham-treated mice. These results suggested that oxycodone relieved not only ongoing pain, but also ambulatory and neuropathic pain, and that the analgesic profile of oxycodone could be different from that of either morphine or fentanyl.
通过将小鼠溶骨性肿瘤细胞（NCTC 2472）植入C3H/HeN小鼠的股骨骨髓腔内，建立了股骨骨癌疼痛模型。体内成像分析显示，植入的肿瘤细胞在14天内逐渐生长。与肿瘤生长相关的是，作为持续疼痛指标的警戒行为随时间依赖性增加。还出现了肢体使用异常和异常性疼痛，分别为动态疼痛和神经性疼痛的指标。在14天所有与疼痛相关的行为明显出现时，评估了羟考酮和其他阿片类药物（如吗啡和芬太尼）的镇痛效果。羟考酮（2 - 20 mg/kg，皮下注射）、吗啡（10 - 50 mg/kg，皮下注射）和芬太尼（0.05 - 0.2 mg/kg，皮下注射）显著降低了警戒行为。羟考酮（5 - 20 mg/kg，皮下注射）和芬太尼（0.1和0.2 mg/kg，皮下注射）显著逆转了肢体使用异常，但吗啡（5 - 50 mg/kg，皮下注射）没有。此外，羟考酮（5 - 20 mg/kg，皮下注射）剂量依赖性地逆转了异常性疼痛，而不影响假手术处理的小鼠。吗啡（50 mg/kg，皮下注射）和芬太尼（0.075 - 0.2 mg/kg，皮下注射）也逆转了异常性疼痛，但吗啡（50 mg/kg，皮下注射）倾向于影响且芬太尼（0.1和0.2 mg/kg，皮下注射）影响假手术处理小鼠的撤药阈值。这些结果表明，羟考酮不仅缓解了持续疼痛，还缓解了动态疼痛和神经性疼痛，且羟考酮的镇痛谱可能与吗啡或芬太尼不同。
