Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Donggu, Gwangju 501-757, Korea.
Anesth Analg. 2011 Oct;113(4):934-40. doi: 10.1213/ANE.0b013e318227824e. Epub 2011 Jul 25.
Although bone cancer-related pain is one of the most disruptive symptoms in patients with advanced cancer, patients are often refractory to pharmacological treatments; thus, more effective treatments for bone cancer pain are needed. We evaluated the analgesic efficacy of and interaction between intrathecal GR89696, a κ(2)-opioid receptor agonist, and interleukin (IL)-10 in a rat model of bone cancer pain.
The rat model of bone cancer pain was produced by right tibia intramedullary injection of rat breast cancer cells, and an intrathecal catheterization was performed. Ten days later, a paw-withdrawal threshold to mechanical stimulus by von Frey hairs was measured using the up-down method, after intrathecal administration of GR89696 and IL-10. The interaction between the 2 drugs was also evaluated using an isobolographic analysis.
Intrathecal GR89696 and IL-10 significantly increased the paw withdrawal threshold of the cancer cell-implanted rat, in a dose-dependent manner, with 50% effective dose values (95% confidence interval) of 50.78 μg (31.80-80.07μg) and 0.83 μg (0.59-1.15 μg), respectively. Isobolographic analysis revealed a synergistic interaction between intrathecal GR89696 and IL-10.
Intrathecally administered GR89696 and IL-10 attenuated bone cancer-induced pain, and the 2 drugs interacted synergistically in the spinal cord. These results raise the intriguing possibility of κ(2)-opioid receptor agonists and IL-10 as a new therapeutic approach for the management of bone cancer-associated pain.
尽管骨癌相关疼痛是晚期癌症患者最具破坏性的症状之一，但患者通常对药物治疗有抗药性；因此，需要更有效的骨癌疼痛治疗方法。我们评估了鞘内给予κ(2)-阿片受体激动剂 GR89696 和白细胞介素 (IL)-10 对骨癌痛大鼠模型的镇痛效果及其相互作用。
通过右胫骨骨髓内注射大鼠乳腺癌细胞制作骨癌痛大鼠模型，并进行鞘内置管。10 天后，采用 von Frey 毛发对机械刺激的足底退缩阈值测定法，通过鞘内给予 GR89696 和 IL-10 来测量。还使用等比图形分析评估了这两种药物之间的相互作用。
鞘内给予 GR89696 和 IL-10 均能显著增加荷瘤大鼠的足底退缩阈值，呈剂量依赖性，其 50%有效剂量值（95%置信区间）分别为 50.78μg（31.80-80.07μg）和 0.83μg（0.59-1.15μg）。等比图形分析显示，鞘内给予 GR89696 和 IL-10 之间存在协同相互作用。
鞘内给予 GR89696 和 IL-10 减轻了骨癌引起的疼痛，并且这两种药物在脊髓中产生协同作用。这些结果提出了一个有趣的可能性，即 κ(2)-阿片受体激动剂和 IL-10 可能成为治疗骨癌相关疼痛的新方法。
