Cell Signaling | Sensory Systems | Neuronal Signaling Mechanisms | Drug Discovery & Design | Molecular Pharmacology | Pain: Basic Science
Suppression of inflammatory and neuropathic pain by uncoupling collapsin response mediator protein 2 (CRMP-2) from the presynaptic calcium channel complex
Rajesh Khanna*, Joel Brittain, Djane Duarte, Sarah Wilson, Weiguo Zhu, Carrie Ballard, Philip Johnson, Naikui Liu, Wenhui Xiong, Matthew Ripsch, Yuying Wang, Jill Fehrenbacher, May Khanna, Chul-Kyu Park, Nickolay Brustovetsky, Ru-Rong Ji, Joyce Hurley, Xiaoming Jin, Anantha Shekhar, Xiao-Ming Xu, Gerry Oxford, Michael Vasko, Fletcher White
*Corresponding author: Rajesh Khanna
Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
F1000Posters 2011, 2: 1816 (poster) [English]
Neuroscience 2011, 12 - 16 Nov 2011, 275.04
The N-type calcium channel is an important target in pain and recent work by our laboratory has identified collapsin response mediator protein 2 (CRMP-2) as a regulator of the channel. In the current study we sought to identify a peptide from CRMP-2 that is able to uncouple CRMP-2 from the calcium channel. This peptide could then be used as a novel way to target the N-type calcium channel in pain.
We identified the CRMP-2 peptide CBD3, which disrupted trafficking of the N-type calcium channel and led to subsequent reduction in calcium currents. The cell penetrant version, TAT-CBD3, was analgesic in animal models of acute, inflammatory, and neuropathic pain.
The efficacy of CBD3 is currently being pursued in a variety of pain models. Mutagenesis, use of alternative cell penetrating peptides, and chemical modifications of CBD3 may lead to increased stability, as well as increased efficacy in pain models.
R. Khanna and J. Brittain have filed a patent for CBD3.
National Institutes of Health (NIH), DE14318-06
National Institutes of Health (NIH), DE017794
National Institutes of Health (NIH), DA026040
National Institutes of Health (NIH), NS051668
National Institutes of Health (NIH), NS050131
National Institutes of Health (NIH), ES017430
Indiana State Department of Health−Spinal Cord and Brain Injury Fund, A70-0-079212
Indiana State Department of Health−Spinal Cord and Brain Injury Fund, A70-9-079138
Indiana University Biomedical Committee– Research Support Funds, 2286501
American Heart Association, SDG5280023
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