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学科主题: 基础医学
题名:
Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice
作者: Bi, Yeping1; Chen, Hui1; Su, Jun1; Cao, Xu1; Bian, Xiling1; Wang, KeWei1,2
关键词: forebrain ; retigabine ; XE-991 ; capsaicin ; acetic acid ; c-Fos ; somatosensory cortex
刊名: MOLECULAR PAIN
发表日期: 2011-10-26
DOI: 10.1186/1744-8069-7-84
卷: 7, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: DEPENDENT PROTEIN-KINASE ; MOUSE-BRAIN ; RAT-BRAIN ; M-CHANNEL ; CENTRAL SENSITIZATION ; GENETIC ENHANCEMENT ; PAIN ; RETIGABINE ; ACTIVATION ; KNOCKOUT
英文摘要:

Background: Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia.

Results: Using a forebrain specific alpha CaMKII promoter, we established a line of transgenic (Tg) mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p.) injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT) mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine.

Conclusions: Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.

语种: 英语
所属项目编号: 30630017 ; 30970919 ; 2007CB512100 ; B07001
项目资助者: National Science Foundation of China ; Ministry of Science Technology of China ; Ministry of Education of China
WOS记录号: WOS:000296918300001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63435
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Dept Mol & Cellular Pharmacol, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Bi, Yeping,Chen, Hui,Su, Jun,et al. Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice[J]. MOLECULAR PAIN,2011,7(1).
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