Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages
Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages
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DOI：
10.3390/ijms20215269
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发表时间：
2019-10
影响因子：
5.6
通讯作者：
A. Stevens;Lu Liu;Dylan Bertovich;J. Janjic;J. Pollock
中科院分区：
文献类型：
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作者：
A. Stevens;Lu Liu;Dylan Bertovich;J. Janjic;J. Pollock
对周围神经损伤的神经炎症反应与慢性疼痛以及神经元、胶质细胞和浸润免疫细胞中 mRNA 分子表达谱的显着变化有关。大鼠坐骨神经的慢性压迫性损伤（CCI）提供了模拟神经性损伤并定量评估个体动物的行为和差异基因表达的机会。此前，我们已经证明，单次静脉注射含有塞来昔布（0.24 mg/kg）的纳米乳剂可减轻坐骨神经炎症并缓解疼痛样行为长达6天。在这里，我们使用这种靶向治疗来探讨疼痛和疼痛缓解状态下对 mRNA 表达变化的影响。从 CCI 动物中回收的坐骨神经组织用于利用定量 PCR 评估 mRNA 表达谱。我们观察到 mRNA 的变化与趋化因子和细胞因子表达减少明显的巨噬细胞募集减少一致。此外，还观察到与巨噬细胞粘附相关的基因，以及神经元和胶质细胞 mRNA 的变化。此外，与接受无药物载体的动物相比，与神经性疼痛相关的基因，包括Maob、Grin2b/NMDAR2b、TrpV3、IL-6、Cacna1b/Cav2.2、Itgam/Cd11b、Scn9a/Nav1.7和Tac1，均被发现在疼痛缓解过程中对载有塞来昔布的纳米乳剂有反应。这些结果表明，通过靶向损伤部位巨噬细胞产生 PGE2，疼痛缓解包括部分逆转与慢性疼痛相关的基因表达谱。
The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b/NMDAR2b, TrpV3, IL-6, Cacna1b/Cav2.2, Itgam/Cd11b, Scn9a/Nav1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE2 at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.