作者
Joel M Brittain, Djane B Duarte, Sarah M Wilson, Weiguo Zhu, Carrie Ballard, Philip L Johnson, Naikui Liu, Wenhui Xiong, Matthew S Ripsch, Yuying Wang, Jill C Fehrenbacher, Stephanie D Fitz, May Khanna, Chul-Kyu Park, Brian S Schmutzler, Bo Myung Cheon, Michael R Due, Tatiana Brustovetsky, Nicole M Ashpole, Andy Hudmon, Samy O Meroueh, Cynthia M Hingtgen, Nickolay Brustovetsky, Ru-Rong Ji, Joyce H Hurley, Xiaoming Jin, Anantha Shekhar, Xiao-Ming Xu, Gerry S Oxford, Michael R Vasko, Fletcher A White, Rajesh Khanna
发表日期
2011/7
期刊
Nature medicine
卷号
17
期号
7
页码范围
822-829
出版商
Nature Publishing Group US
简介
The use of N-type voltage-gated calcium channel (CaV2.2) blockers to treat pain is limited by many physiological side effects. Here we report that inflammatory and neuropathic hypersensitivity can be suppressed by inhibiting the binding of collapsin response mediator protein 2 (CRMP-2) to CaV2.2 and thereby reducing channel function. A peptide of CRMP-2 fused to the HIV transactivator of transcription (TAT) protein (TAT-CBD3) decreased neuropeptide release from sensory neurons and excitatory synaptic transmission in dorsal horn neurons, reduced meningeal blood flow, reduced nocifensive behavior induced by formalin injection or corneal capsaicin application and reversed neuropathic hypersensitivity produced by an antiretroviral drug. TAT-CBD3 was mildly anxiolytic without affecting memory retrieval, sensorimotor function or depression. At doses tenfold higher than that required to reduce …
学术搜索中的文章
JM Brittain, DB Duarte, SM Wilson, W Zhu, C Ballard… - Nature medicine, 2011