The Use of Inhibitors of Mechanosensitive Ion Channels as Local Inhibitors of Peripheral Pain
Annual rept. 25 Feb 2012-24 Feb 2013
STATE UNIV OF NEW YORK COLL AT BUFFALO
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This is a basic research project designed to understand the role of mechanically sensitive excitatory ion channels MSC in the pathology of chronic pain, and the use of a small pepti de inhibitor of these channels called GsMTx4 to treatment peripheral pain. Our first goal is to develop an in vitro assay using single neurons to study the prop erties of MSCs and to determine the affinity of GsMTx4 and muta nt analogs for neuronal MSCs. We have learned to prepare dorsal root ganglion neurons DRG from mouse spinal cord and have determined the types of MSCs expressed and the frequ ency of their occurrence in the cell-attached and outside-out patch assay. We have also designed a second assay for MSC activity by pressing on DRG with a prec ision controlled motion glass probe while measuring whole cell curr ents as a independent measure of the MSC activity. Stress on the internal cy toskeleton may play a critical role in the activation of MSCs on the surface and so we will measure stress changes in the proteins that make up the cytoskeleton of DRGs using a new FRET based stress probe we have made which can be inserted into the sequence of cytoskeletal pr oteins to report stress. We have tried to reproduce the pub lished findings of others showing GsMTx4 analgesic activity in whole an imals by treating inflamed tissue in mice, but were unable to d o so. However, we have learned new information about the pharmaco kinetics of GsMTx4 that will be used to redesign the study.
- Medicine and Medical Research