Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Mol Brain. 2012 Jun 9;5:21. doi: 10.1186/1756-6606-5-21.
The most frequent pain in patients with metastatic breast and prostate cancer is bone pain, which can be severe and difficult to treat. The mechanisms underlying this pain remain unclear. Here we investigated the role of c-jun N-terminal kinase (JNK) pathway in the spinal cord in cancer-induced bone pain (CIBP).
In this study, we used an established rat CIBP model to investigate the possible role of JNK activation in the spinal cord. After intra-tibial inoculation with Walker 256 rat mammary gland carcinoma cells, the rats displayed mechanical allodynia on day 5, which lasted to day 16. The activation of JNK in neurons and astrocytes in the spinal cord was found on day 12 and day 16 after intra-tibial inoculation with carcinoma cells. A single intrathecal injection with JNK inhibitor SP600125 by lumbar puncture attenuated mechanical allodynia on day 12, and repeated intrathecal injection of SP600126 from day 10 to day 14 had a cumulative analgesic effect on CIBP.
Taken together, our results demonstrated for the first time that JNK activation in the spinal cord is required in the maintenance of CIBP. Inhibition of the spinal JNK pathway may provide a new therapy for CIBP management.
转移性乳腺癌和前列腺癌患者最常见的疼痛是骨痛，这种疼痛可能很严重且难以治疗。其潜在机制尚不清楚。在这里，我们研究了脊髓中 c-jun N 末端激酶（JNK）通路在癌性骨痛（CIBP）中的作用。
在这项研究中，我们使用了已建立的大鼠 CIBP 模型来研究 JNK 激活在脊髓中的可能作用。在胫骨内接种 Walker 256 大鼠乳腺癌细胞后，大鼠在第 5 天出现机械性痛觉过敏，持续到第 16 天。在胫骨内接种癌细胞后 12 天和 16 天，发现脊髓神经元和星形胶质细胞中的 JNK 被激活。通过腰椎穿刺单次鞘内注射 JNK 抑制剂 SP600125 可减轻第 12 天的机械性痛觉过敏，从第 10 天到第 14 天重复鞘内注射 SP600126 对 CIBP 具有累积镇痛作用。
综上所述，我们的研究结果首次表明，脊髓中 JNK 的激活是 CIBP 维持所必需的。抑制脊髓 JNK 通路可能为 CIBP 治疗提供一种新的治疗方法。
