关键词：神经节；动力学；疼痛；激活
摘 要：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 properties 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 frequency 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 precision controlled motion glass probe while measuring whole cell currents as a independent measure of the MSC activity. Stress on the internal cytoskeleton 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 proteins to report stress. We have tried to reproduce the published findings of others showing GsMTx4 analgesic activity in whole animals by treating inflamed tissue in mice, but were unable to do so. However, we have learned new information about the pharmaco kinetics of GsMTx4 that will be used to redesign the study.