Department of Histology and Embryology, Taishan Medical University, Taian, 271000, China.
Department of Human Anatomy, Taishan Medical University, Taian, 271000, China.
J Neuroinflammation. 2018 Sep 25;15(1):280. doi: 10.1186/s12974-018-1316-0.
Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood.
Wistar rats were employed for the establishment of the chronic constriction injury (CCI) models. Using the Illumina HiSeq 4000 platform, we examined differentially expressed genes (DEGs) in the rat dorsal horn by RNA sequencing (RNA-seq) between CCI and control groups. Then, enrichment analyses were performed for these DEGs using Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Hierarchical Cluster, and protein-protein interaction (PPI) network.
A total of 63 DEGs were found significantly changed with 56 upregulated (e.g., Cxcl13, C1qc, Fcgr3a) and 7 downregulated (e.g., Dusp1) at 14 days after CCI. Quantitative reverse-transcribed PCR (qRT-PCR) verified changes in 13 randomly selected DEGs. GO and KEGG biological pathway analyses showed that the upregulated DEGs were mostly enriched in immune response-related biological processes, as well as 14 immune- and inflammation-related pathways. The downregulated DEGs were enriched in inactivation of mitogen-activated protein kinase (MAPK) activity. PPI network analysis showed that Cd68, C1qc, C1qa, Laptm5, and Fcgr3a were crucial nodes with high connectivity degrees. Most of these genes which have previously been linked to immune and inflammation-related pathways have not been reported in neuropathic pain (e.g., Laptm5, Fcgr3a).
Our results revealed that immune and defense pathways may contribute to the generation of neuropathic pain after CCI. These mRNAs may represent new therapeutic targets for the treatment of neuropathic pain.
神经病理性疼痛是由神经系统损伤引起的，导致异常疼痛，这与感觉通路中的基因表达变化有关。然而，其分子机制尚不完全清楚。
使用 Wistar 大鼠建立慢性缩窄性损伤（CCI）模型。我们通过 RNA 测序（RNA-seq）在 CCI 组和对照组大鼠背角中检测到差异表达基因（DEGs），并使用基因本体论（GO）功能、京都基因与基因组百科全书（KEGG）通路、层次聚类和蛋白质-蛋白质相互作用（PPI）网络对这些 DEGs 进行富集分析。
共发现 63 个 DEGs 存在显著差异，其中 56 个上调（如 Cxcl13、C1qc、Fcgr3a），7 个下调（如 Dusp1），在 CCI 后 14 天。定量逆转录 PCR（qRT-PCR）验证了 13 个随机选择的 DEGs 的变化。GO 和 KEGG 生物途径分析表明，上调的 DEGs 主要富集在免疫反应相关的生物学过程中，以及 14 个免疫和炎症相关途径。下调的 DEGs 富集在丝裂原激活蛋白激酶（MAPK）活性失活。PPI 网络分析表明，Cd68、C1qc、C1qa、Laptm5 和 Fcgr3a 是具有高连接度的关键节点。这些基因中的大多数以前与免疫和炎症相关途径有关，但在神经病理性疼痛中尚未报道（如 Laptm5、Fcgr3a）。
我们的研究结果表明，免疫和防御途径可能有助于 CCI 后神经病理性疼痛的发生。这些 mRNA 可能代表治疗神经病理性疼痛的新治疗靶点。
