IR@PKUHSC  > 北京大学基础医学院  > 神经生物学系
学科主题基础医学
WNT signaling underlies the pathogenesis of neuropathic pain in rodents
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
2013-05-01
DOI10.1172/JCI65364
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
WOS记录号WOS:000319025100044
项目编号PRF-BSR10110607 ; NSFC81271241 ; NSFC81000475 ; BMU20120310
资助机构Parker Research Foundation ; National Natural Science Foundation of China ; Peking University Health Science Center
引用统计
被引频次:70[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56141
专题北京大学基础医学院_神经生物学系
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
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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.
APA Zhang, Yan-Kai,Huang, Zhi-Jiang,Liu, Su,Liu, Yue-Peng,Song, Angela A.,&Song, Xue-Jun.(2013).WNT signaling underlies the pathogenesis of neuropathic pain in rodents.JOURNAL OF CLINICAL INVESTIGATION,123(5),2268-2286.
MLA Zhang, Yan-Kai,et al."WNT signaling underlies the pathogenesis of neuropathic pain in rodents".JOURNAL OF CLINICAL INVESTIGATION 123.5(2013):2268-2286.
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