Ni Kun, Zhou Yu, Sun Yu-e, Liu Yue, Gu Xiao-ping, Ma Zheng-liang
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical College of Nanjing University, Nanjing 210008, Jiangsu Province, China.
Pharmacol Biochem Behav. 2014 Jul;122:228-33. doi: 10.1016/j.pbb.2014.03.026. Epub 2014 Apr 12.
Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. Here we report a means by infusion of the selected peptide Myr-RC-13 intrathecally to attenuate bone cancer pain. The results showed that inoculation of fibrosarcoma NCTC 2472 cells into the femur cavity of C3H/HeJ mice induced progressive bone cancer pain and resulted in up-regulation of KIF17 and NR2B in the spinal cord. In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.
尽管骨癌疼痛是一种常见的顽固性临床症状，但其潜在机制仍不清楚。越来越多的证据表明，脊髓中含有2B亚基（NR2B）的N-甲基-D-天冬氨酸（NMDA）受体与骨癌疼痛有关。我们的初步研究表明，鞘内注射融合肽Myr-RC-13可破坏脊髓KIF17/mLin10相互作用，这是KIF17介导的NR2B转运的重要组成部分。在此，我们报告一种通过鞘内注入选定的肽Myr-RC-13来减轻骨癌疼痛的方法。结果显示，将纤维肉瘤NCTC 2472细胞接种到C3H/HeJ小鼠的股骨腔内可诱发进行性骨癌疼痛，并导致脊髓中KIF17和NR2B上调。此外，重复脊髓给予Myr-RC-13可减轻骨癌相关的机械性异常性疼痛和自发疼痛行为，并下调脊髓KIF17和NR2B的表达。最后，我们的结果表明，选定的肽Myr-RC-13能够通过降低脊髓KIF17和NR2B的表达来减轻骨癌疼痛。因此，选定的肽Myr-RC-13可能是一种治疗骨癌疼痛的潜在镇痛策略。
