Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain
文献类型：期刊论文
| 作者 | Xie, Zili7,8; Feng, Jing6,7,8; Cal, Tao5,7,8; McCarthy, Ronald4; Eschbach, Mark D., III3; Wang, Yuhui2,7,8; Zhao, Yonghui7,8; Yi, Zhihua1,7,8; Zang, Kaikai7,8; Yuan, Yi7,8 |
| 刊名 | JCI INSIGHT
 |
| 出版日期 | 2022-05-23 |
| 卷号 | 7期号:10页码:19 |
| DOI | 10.1172/jci.insight.149107 |
| 通讯作者 | Hu, Hongzhen(hongzhen.hu@wustl.edu) |
| 英文摘要 | Pain emanating from the female reproductive tract is notoriously difficult to treat, and the prevalence of transient pelvic pain has been placed as high as 70%???80% in women surveyed. Although sex hormones, especially estrogen, are thought to underlie enhanced pain perception in females, the underlying molecular and cellular mechanisms are not completely understood. Here, we showed that the pain-initiating TRPA1 channel was required for pain-related behaviors in a mouse model of estrogen-induced uterine pain in ovariectomized female mice. Surprisingly, 2-and 4-hydroxylated estrogen metabolites (2-and 4-HEMs) in the estrogen hydroxylation pathway, but not estrone, estradiol, or 16-HEMs, directly increased nociceptor hyperactivity through TRPA1 and TRPV1 channels, and picomolar concentrations of 2-and 4-hydroxylation estrone (2-or 4-OHE1) could sensitize TRPA1 channel function. Moreover, both TRPA1 and TRPV1 were expressed in uterine-innervating primary nociceptors, and their expression was increased in the estrogen induced uterine pain model. Importantly, pretreatment with 2-or 4-OHE1 recapitulated estrogen induced uterine pain-like behaviors, and intraplantar injections of 2-and 4-OHE1 directly produced a TRPA1-dependent mechanical hypersensitivity. Our findings demonstrated that TRPA1 is critically involved in estrogen-induced uterine pain-like behaviors, which may provide a potential drug target for treating female reproductive tract pain. |
| WOS关键词 | RECEPTOR POTENTIAL CHANNELS ; CHRONIC WIDESPREAD PAIN ; SEX-DIFFERENCES ; GENDER-DIFFERENCES ; UP-REGULATION ; TRPV1 ; ACTIVATION ; TRPA1 ; EXPRESSION ; HORMONES |
| 资助项目 | NIH[R01DK103901] ; NIH[R01AR077183] ; NIH[R01AA027065] ; Department of Anesthesiology, Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine in St. Louis |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| WOS记录号 | WOS:000802211300001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/301119]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Hongzhen |
| 作者单位 | 1.Nanchang Univ, Coll Med, Dept Nursing, Nanchang, Jiangxi, Peoples R China 2.Chinese Acad Med Sci & Peking Union Med Coll, Dept Anesthesiol Plast Surg Hosp, Beijing, Peoples R China 3.Univ Illinois, Neurosci Program, Dept Bioengn, Urbana, IL USA 4.Washington Univ, Sch Med, Ctr Reprod Hlth Sci, Dept Obstet & Gynecol, St Louis, MO USA 5.Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Neurol & Psychiat Res & Drug Discovery, Shanghai, Peoples R China 7.Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO USA 8.Washington Univ, Sch Med, Ctr Study Itch & Sensory Disorders, St Louis, MO 63110 USA |
| 推荐引用方式 GB/T 7714 | Xie, Zili,Feng, Jing,Cal, Tao,et al. Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain[J]. JCI INSIGHT,2022,7(10):19. |
| APA | Xie, Zili.,Feng, Jing.,Cal, Tao.,McCarthy, Ronald.,Eschbach, Mark D., III.,...&Hu, Hongzhen.(2022).Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain.JCI INSIGHT,7(10),19. |
| MLA | Xie, Zili,et al."Estrogen metabolites increase nociceptor hyperactivity in a mouse model of uterine pain".JCI INSIGHT 7.10(2022):19. |
入库方式： OAI收割
来源：上海药物研究所
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