CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain.
CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain.
复制标题
CXCR4 拮抗剂 AMD3100 引发镇痛作用并恢复 GlyRα3 表达以对抗神经性疼痛
DOI：
10.2147/jpr.s139619
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
Ma K
中科院分区：
文献类型：
--
作者：
Liu X;Liu H;Dai L;Ma B;Ma K
趋化因子CXCL12及其受体CXCR4在神经发生和神经元分化中起关键作用。最近，一些报道暗示了这种趋化因子信号在多种疼痛的发病机制。然而，其在神经性疼痛（NP）中的作用在很大程度上仍不清楚。本研究探讨了CXCR4在大鼠L5脊髓神经结扎（SNL）模型中脊髓（SC）背角（DH）中的分布和功能。大鼠接受鞘内重复注射CXCR4拮抗剂AMD3100。行为评估采用传统的“上下法”进行。采用酶联免疫吸附法测定脊髓CXCL12含量。免疫荧光和Western blot检测CXCR4在SC中的表达和分布。Western blot和免疫荧光法检测GlyRα3的表达。SNL诱导脊髓DH中CXCL12-CXCR4的激活。鞘内注射AMD3100可减轻慢性NP对SNL的影响（P<0.01）。在脊髓DH中，CXCR4与glyr α3阳性神经元共定位，比例为bb0.97%。同时，AMD3100在第14天和第21天挽救了GlyRα3表达的下降（与SNL组相比P<0.01）。CXCR4拮抗剂可引起镇痛作用，恢复GlyRα3等抑制NP的神经传递。
Chemokine CXCL12 and its receptor CXCR4 have been reported to play a critical role in neurogenesis and neuronal differentiation. Recently, some reports have implicated this chemokine signaling in the pathogenesis of many kinds of pain. However, its role in neuropathic pain (NP) is still largely unclear. This study explored the distribution and function of CXCR4 in spinal cord (SC) dorsal horn (DH) in a rat L5 spinal nerve ligation (SNL) model. Rats received repeated intrathecal injection of CXCR4 antagonist AMD3100. Behavioral assessments were conducted using a traditional “up–down” method. The spinal CXCL12 contents were measured by enzyme linked immunosorbent assay. The expression and distribution of CXCR4 in the SC were determined by immunoflurescence and Western blot. GlyRα3 expressions were also measured by Western blot or immunofluorescence. SNL induced CXCL12–CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (P<0.01). CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (P<0.01 vs the SNL group on Day 14 and Day 21). CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP.