Liu Bao-Wen, Li Zhi-Xiao, He Zhi-Gang, Liu Cheng, Xiong Jun, Xiang Hong-Bing
Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hepatobiliary Surgery Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Oncotarget. 2017 Aug 10;8(43):74423-74433. doi: 10.18632/oncotarget.20148. eCollection 2017 Sep 26.
Spinal cord plays a central role in the development and progression of pathogenesis of obstinate pruritus. In the current study, four groups of adult male C57Bl/6 mice were investigated; one group treated with saline, while the other groups intradermally injected with compound 48/80, histamine, α-Me-5-HT and capsaicin (algogenic substance), respectively. The intradermal microinjection of pruritic and algogenic compound resulted in a dramatic increase in the itch/algogenic behavior. Analysis of the microarray data showed that 15 genes in spinal cord (C5-C8) were differentially expressed between control group and 48/80 group, in which 9 genes were up-regulated and 6 genes were down-regulated. Furthermore, the results of RT-qPCR validation studies in C5-C8 spinal cord revealed that the 9 mRNA (Sgk1, Bag4, Fos, Ehd2, Edn3, Wdfy, Corin, 4921511E18Rik and 4930423020Rik) showed very different patterns for these different drugs, especially when comparing α-Me-5-HT and capsaicin. In three itch models, Fos and Ehd2 were up-regulated whereas Corin, 4921511E18Rik and 4930423020Rik were down-regulated. Furthermore, Corin and 4930423020Rik were down-regulated in itch model group compared to capsaicin group. Thus the application of microarray technique, coupled with RT-qPCR validation, further explain the mechanism behind itching evoked by pruritic compounds. It can contribute to our understanding of pharmacological methods for prevention or treatment of obstinate pruritus.
脊髓在顽固性瘙痒发病机制的发展和进程中起着核心作用。在本研究中,对四组成年雄性C57Bl/6小鼠进行了研究;一组用生理盐水处理,而其他组分别皮内注射化合物48/80、组胺、α-甲基-5-羟色胺和辣椒素(致痛物质)。皮内微量注射瘙痒和致痛化合物导致瘙痒/致痛行为显著增加。微阵列数据分析表明,对照组和48/80组之间脊髓(C5 - C8)中有15个基因差异表达,其中9个基因上调,6个基因下调。此外,C5 - C8脊髓中RT-qPCR验证研究结果显示,这9种mRNA(Sgk1、Bag4、Fos、Ehd2、Edn3、Wdfy、Corin、4921511E18Rik和4930423020Rik)在这些不同药物作用下表现出非常不同的模式,尤其是比较α-甲基-5-羟色胺和辣椒素时。在三种瘙痒模型中,Fos和Ehd2上调,而Corin, 4921511E18Rik和4930423020Rik下调。此外,与辣椒素组相比,瘙痒模型组中Corin和4930423020Rik下调。因此,微阵列技术与RT-qPCR验证相结合,进一步解释了瘙痒化合物诱发瘙痒的机制。这有助于我们理解预防或治疗顽固性瘙痒的药理学方法。