Involvement of EphB1 receptor/ephrinB1 ligand in bone cancer pain
Involvement of EphB1 receptor/ephrinB1 ligand in bone cancer pain
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DOI：
10.1016/j.neulet.2011.04.008
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发表时间：
2011-06-08
影响因子：
2.5
通讯作者：
Tan, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Dong, Yan;Mao-Ying, Qi-Liang;Tan, Zhi-Ming
在先前的研究中，Eph/ephrin系统被证明参与炎症性和神经性疼痛的调节。本研究旨在探讨脊髓Eph/ephrin信号通路是否参与骨癌性疼痛（BCP）大鼠脊柱炎性细胞因子的调节。采用Walker 256乳腺癌细胞胫骨内接种诱导BCP。测定EphB1/ephrinB1在大鼠脊髓（SC）和背根神经节（DRG）中的表达。接种16天后，在鞘内给予EphB1- fc （EphB1受体阻滞剂，10 μ g）后，检测疼痛缓解效果和炎症细胞因子mRNA水平。结果表明，接种Walker 256后，SC中EphB1/ephrinB1的表达量显著升高，DRG中ephrinB1的表达量显著降低。鞘内给药EphB1-Fc可明显减轻骨癌所致的机械性异常痛。此外，RT-PCR分析显示，接种Walker 256后16天，SC中IL-1 β、IL-6和tnf - α mRNA水平显著升高，并被鞘内注射EphB1-Fc显著抑制。我们认为，Eph/ephrin可能通过调节脊髓炎症细胞因子的表达，参与了机械性异常性痛的维持。本研究提示Eph/ephrin信号可能是治疗BCP的潜在靶点。2011爱思唯尔爱尔兰有限公司版权所有。
In prior studies, Eph/ephrin system was demonstrated to be involved in inflammatory and neuropathic pain modulation. The present study was to investigate whether the spinal Eph/ephrin signaling was involved in modulation of spinal inflammatory cytokines in bone cancer pain (BCP) of rats. BCP was induced by intra-tibial inoculation of Walker 256 mammary gland carcinoma cells. The expressions of EphB1/ephrinB1 in spinal cord (SC) and dorsal root ganglia (DRG) were determined. At 16 days post inoculation, the pain relieving effect and the mRNA levels of inflammatory cytokines were detected after intrathecal administration of EphB1-Fc (blocker of EphB1 receptor, 10 mu g). The results showed that the EphB1/ephrinB1 expression was significantly increased in SC, but ephrinB1 was decreased in DRG after Walker 256 inoculation. The mechanical allodynia induced by bone cancer was significantly alleviated by intrathecal administration of EphB1-Fc. Furthermore, the RT-PCR analysis showed that the mRNA levels of IL-1 beta, IL-6 and TNF-alpha were significantly increased at 16 days post Walker 256 inoculation and were significantly suppressed by intrathecal administration of EphB1-Fc in SC. We concluded that Eph/ephrin might be involved in the maintenance of mechanical allodynia, via modulating the expression of spinal inflammatory cytokines, in the present rat model of BCP. This study suggested that Eph/ephrin signaling would be a potential target for the treatment of BCP. (C) 2011 Elsevier Ireland Ltd. All rights reserved.