趋化因子受体4（CXCR4）拮抗剂AMD3100可产生镇痛作用，并恢复甘氨酸受体α3（GlyRα3）的表达以对抗神经性疼痛。
CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain.
作者信息
Liu Xiaoming, Liu Hongjun, Dai Lihua, Ma Bingjie, Ma Ke
机构信息
Pain Management Center, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
出版信息
J Pain Res. 2017 Sep 7;10:2205-2212. doi: 10.2147/JPR.S139619. eCollection 2017.
OBJECTIVE
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.
METHODS
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.
RESULTS
SNL induced CXCL12-CXCR4 activation in the spinal DH. Intrathecal administration of AMD3100 alleviated the chronic NP against SNL (<0.01). CXCR4 was colocalized with GlyRα3-positive neurons in the spinal DH at ratio >97%. Meanwhile, AMD3100 rescued the decrease of GlyRα3 expression (<0.01 vs the SNL group on Day 14 and Day 21).
CONCLUSION
CXCR4 antagonist can elicit analgesic effects and restore the inhibitory neurotransmission such as GlyRα3 against NP.
目的
据报道，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，一些报道表明这种趋化因子信号传导与多种疼痛的发病机制有关。然而，其在神经性疼痛（NP）中的作用仍 largely不清楚。本研究在大鼠L5脊髓神经结扎（SNL）模型中探索了CXCR4在脊髓（SC）背角（DH）中的分布和功能。
方法
大鼠接受CXCR4拮抗剂AMD3100的反复鞘内注射。使用传统的“上下”方法进行行为评估。通过酶联免疫吸附测定法测量脊髓CXCL12含量。通过免疫荧光和蛋白质印迹法测定SC中CXCR4的表达和分布。还通过蛋白质印迹或免疫荧光测量GlyRα3表达。
结果
SNL诱导脊髓DH中的CXCL12-CXCR4激活。鞘内给予AMD3100可减轻针对SNL的慢性NP（<0.01）。CXCR4与脊髓DH中GlyRα3阳性神经元共定位，比例>97%。同时，AMD3100挽救了GlyRα3表达的降低（与第14天和第21天的SNL组相比，<0.01）。
结论
CXCR4拮抗剂可引发镇痛作用，并恢复针对NP的抑制性神经传递，如GlyRα3。
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