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学科主题: 基础医学
题名:
WNT signaling underlies the pathogenesis of neuropathic pain in rodents
作者: Zhang, Yan-Kai1; Huang, Zhi-Jiang1; Liu, Su1,2; Liu, Yue-Peng1,2; Song, Angela A.3; Song, Xue-Jun1,2
刊名: JOURNAL OF CLINICAL INVESTIGATION
发表日期: 2013-05-01
DOI: 10.1172/JCI65364
卷: 123, 期:5, 页:2268-2286
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: BONE CANCER PAIN ; NEURAL CREST MIGRATION ; DORSAL-ROOT GANGLIA ; SPINAL-CORD ; EPHB RECEPTOR ; BETA-CATENIN ; PHYSICAL-DEPENDENCE ; COLORECTAL-CANCER ; NERVOUS-SYSTEM ; UP-REGULATION
英文摘要:

Treating neuropathic pain is a major clinical challenge, and the underlying mechanisms of neuropathic pain remain elusive. We hypothesized that neuropathic pain-inducing nerve injury may elicit neuronal alterations that recapitulate events that occur during development. Here, we report that WNT signaling, which is important in developmental processes of the nervous system, plays a critical role in neuropathic pain after sciatic nerve injury and bone cancer in rodents. Nerve injury and bone cancer caused a rapid-onset and long-lasting expression of WNTs, as well as activation of WNT/frizzled/beta-catenin signaling in the primary sensory neurons, the spinal dorsal horn neurons, and astrocytes. Spinal blockade of WNT signaling pathways inhibited the production and persistence of neuropathic pain and the accompanying neurochemical alterations without affecting normal pain sensitivity and locomotor activity. WNT signaling activation stimulated production of the proinflammatory cytokines IL-18 and TNF-alpha and regulated the NR2B glutamate receptor and Ca2+-dependent signals through the beta-catenin pathway in the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the WNT signaling pathway may be an effective approach for treating neuropathic pain, including bone cancer pain.

语种: 英语
所属项目编号: PRF-BSR10110607 ; NSFC81271241 ; NSFC81000475 ; BMU20120310
项目资助者: Parker Research Foundation ; National Natural Science Foundation of China ; Peking University Health Science Center
WOS记录号: WOS:000319025100044
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56141
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, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Columbia Univ, Columbia Coll, New York, NY USA
3.Parker Univ, Res Inst, Dept Neurobiol, Dallas, TX 75229 USA

Recommended Citation:
Zhang, Yan-Kai,Huang, Zhi-Jiang,Liu, Su,et al. WNT signaling underlies the pathogenesis of neuropathic pain in rodents[J]. JOURNAL OF CLINICAL INVESTIGATION,2013,123(5):2268-2286.
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