Ren Fei, Jiao Hena, Cai Hongwei
Department of Anesthesiology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, People's Republic of China.
Cell Biochem Biophys. 2015 Jun;72(2):611-6. doi: 10.1007/s12013-014-0510-7.
The purpose of this study is to investigate the analgesic effect of intrathecal injection of chemokine receptor CCR2 antagonist RS102895, and its effect on spinal expression of N-methyl-D-aspartate (NMDA) receptor NR2B subunit, neuronal nitric oxide synthase (nNOS), and SIGIRR in a rat model of bone cancer pain (BCP). A rat model of BCP was established by intro-tibial inoculation of W256 breast cancer cells. Female SD rats were randomly divided into five groups (n = 10 each): Sham group, Sham + RS102895 group, BCP group, BCP + RS102895 group, and BCP + DMSO group. Rats received intrathecal injections of either RS102895 (3 g/l) 10 μl or 10 % DMSO 10 μl on day 9 to day 20 after operation. Pain thresholds of mechanical stimulation and thermal stimulation of each group were measured one day before and at 3rd, 6th, 9th, 12th, 15th, and 20th days after surgery. Spinal expression of NR2B, nNOS, and SIGIRR was detected by RT-PCR and Western blot. CCR2 antagonist RS102895 can suppress the pain induced by both mechanical and thermal stimulation in rats with BCP. Spinal expression of CCR2, NR2B, and nNOS was significantly up-regulated, while SIGIRR was down-regulated in BCP rats, and intrathecal injection of RS102895 effectively reversed the pattern of NR2B, nNOS, and SIGIRR expression in spinal cord. Analgesic effects of CCR2 antagonist RS102895 in BCP rats may be related to its downregulation of signal transduction pathway of NMDAR/nNOS and upregulation of Toll-interleukin-1 receptor member SIGIRR.
本研究旨在探讨鞘内注射趋化因子受体CCR2拮抗剂RS102895的镇痛作用及其对骨癌痛（BCP）大鼠模型脊髓中N-甲基-D-天冬氨酸（NMDA）受体NR2B亚基、神经元型一氧化氮合酶（nNOS）和单免疫球蛋白白细胞介素-1受体相关分子（SIGIRR）表达的影响。通过胫骨内接种W256乳腺癌细胞建立BCP大鼠模型。将雌性SD大鼠随机分为五组（每组n = 10）：假手术组、假手术+RS102895组、BCP组、BCP+RS102895组和BCP+二甲基亚砜（DMSO）组。术后第9天至第20天，大鼠接受鞘内注射10 μl RS102895（3 μg/μl）或10% DMSO 10 μl。在手术前1天以及术后第3、6、9、12、15和20天测量每组的机械刺激和热刺激疼痛阈值。通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测脊髓中NR2B、nNOS和SIGIRR的表达。CCR2拮抗剂RS102895可抑制BCP大鼠机械和热刺激诱导的疼痛。BCP大鼠脊髓中CCR2、NR2B和nNOS的表达显著上调，而SIGIRR表达下调，鞘内注射RS102895可有效逆转脊髓中NR2B、nNOS和SIGIRR的表达模式。CCR2拮抗剂RS102895对BCP大鼠的镇痛作用可能与其下调NMDAR/nNOS信号转导通路以及上调Toll样白细胞介素-1受体成员SIGIRR有关。
