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Dataset of (±)-NBI-74330 (CXCR3 antagonist) influence on chemokines under neuropathic pain

机译:(±)-NBI-74330(CXCR3拮抗剂)对神经性疼痛下趋化因子的影响的数据集

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Our data give evidence that CXCR3 ligands exhibit pronociceptive properties and play an important role in the initiation, development and maintenance of neuropathic pain. Moreover, intrathecal administration of each CXCR3 ligand induced hypersensitivity reactions in naive mice and of its neutralizing antibodies diminished neuropathic pain syndrome in CCI-exposed mice. Furthermore, our results indicate that selective CXCR3 antagonist (±)-NBI-74330 reduced the neuropathic pain-related behaviour and also enhanced morphine analgesic potency in CCI-exposed rats. Interestingly, our data show that (±)-NBI-74330 administration diminished the spinal IBA1 and, in parallel, downregulated CXCL4, CXCL9 and CXCL10. In addition, CXCR3 antagonist increased the spinal GFAP, what correlates with upregulation of CXCR3 and CXCL11. Moreover, in DRG (±)-NBI-74330 did not change IBA1 and GFAP positive cells activation, however downregulated also CXCL9. CXCR3 and CXCL10 were co-localized predominantly with neuronal marker in the spinal cord. Summing up, chronic (±)-NBI-74330 intrathecal injection promotes beneficial analgesic effects in rat neuropathic pain model, as described in details in “Pharmacological blockade of CXCR3 by (±)-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness - evidence fromin vivoandin vitrostudies” (Piotrowska et al., 2018).
机译:我们的数据提供证据表明CXCR3配体具有伤害感受特性,并且在神经性疼痛的发生,发展和维持中起重要作用。此外,鞘内注射每种CXCR3配体可在幼稚小鼠中引起超敏反应及其中和抗体,可减轻CCI暴露小鼠的神经性疼痛综合征。此外,我们的结果表明,选择性CXCR3拮抗剂(±)-NBI-74330减少了CCI暴露大鼠的神经性疼痛相关行为,并增强了吗啡镇痛作用。有趣的是,我们的数据显示,(±)-NBI-74330给药可减少脊髓IBA1,并同时下调CXCL4,CXCL9和CXCL10。此外,CXCR3拮抗剂增加了脊髓GFAP,这与CXCR3和CXCL11的上调相关。此外,在DRG(±)-NBI-74330中,IBA1和GFAP阳性细胞的激活没有改变,但是CXCL9也被下调。 CXCR3和CXCL10主要与神经元标记在脊髓中共定位。总结起来,慢性(±)-NBI-74330鞘内注射可促进大鼠神经性疼痛模型的有益止痛作用,如“(±)-NBI-74330对CXCR3的药理学阻断作用可减轻神经性疼痛并增强阿片类药物的有效性”中详细介绍-证据来自体内和体外研究”(Piotrowska等,2018)。

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