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疼痛基因的调控——辣椒素与树脂毒素:转录组数据的重新评估

Regulation of Pain Genes-Capsaicin vs Resiniferatoxin: Reassessment of Transcriptomic Data.

作者信息

Singla Rajeev K, Sultana Adiba, Alam Md Shahin, Shen Bairong

机构信息

Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

Center for Systems Biology, Soochow University, Suzhou, China.

出版信息

Front Pharmacol. 2020 Oct 29;11:551786. doi: 10.3389/fphar.2020.551786. eCollection 2020.

DOI:10.3389/fphar.2020.551786
PMID:33192502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7658921/
Abstract

Emerging evidence has shown a strong association between neuropathic pain and chronic diseases. In recent years, the treatment of neuropathic pain has attracted more attention. Natural products, such as capsaicin and resiniferatoxin, have been well utilized to treat this disease. In this study, we aim to compare the regulatory effects of capsaicin and resiniferatoxin on pain-related genes as well as on genes with no direct association with pain. Public transcriptomic and microarray data on gene expression in the dorsal root ganglia and genes associated with TRPV1 (+) neurons were obtained from the GEO database and then analyzed. Differentially expressed genes were selected for further functional analysis, including pathway enrichment, protein-protein interaction, and regulatory network analysis. Pain-associated genes were extracted with the reference of two pain gene databases and the effects of these two natural drugs on the pain-associated genes were measured. The results of our research indicate that as compared to capsaicin, resiniferatoxin (RTX) regulates more non pain-associated genes and has a negative impact on beneficial genes (off-targets) which are supposed to alleviate nociception and hypersensitivity by themselves. So, based on this study, we may conclude that capsaicin may be less potent when compared to RTX, but it will elicit considerably less adverse effects too. Thereby confirming that capsaicin could be used for the efficient alleviation of neuropathic pain with possibly fewer side effects.

摘要

新出现的证据表明,神经性疼痛与慢性疾病之间存在密切关联。近年来,神经性疼痛的治疗受到了更多关注。天然产物,如辣椒素和树脂毒素,已被很好地用于治疗这种疾病。在本研究中,我们旨在比较辣椒素和树脂毒素对疼痛相关基因以及与疼痛无直接关联的基因的调节作用。从基因表达综合数据库(GEO数据库)获取了背根神经节中基因表达的公共转录组和微阵列数据以及与瞬时受体电位香草酸亚型1(TRPV1)(+)神经元相关的基因,然后进行分析。选择差异表达基因进行进一步的功能分析,包括通路富集、蛋白质-蛋白质相互作用和调控网络分析。参照两个疼痛基因数据库提取疼痛相关基因,并测定这两种天然药物对疼痛相关基因的影响。我们的研究结果表明,与辣椒素相比,树脂毒素(RTX)调节更多与疼痛无关的基因,并且对那些本应自身减轻伤害感受和超敏反应的有益基因(脱靶效应)有负面影响。因此,基于本研究,我们可以得出结论,与RTX相比,辣椒素的效力可能较低,但它引起的不良反应也会少得多。从而证实辣椒素可用于有效缓解神经性疼痛,且副作用可能较少。

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