Do acid-sensing ion channels trigger ischemic pain?

Oregon Health & Science University, Portland OR

Investigators

Abstract

DESCRIPTION Ischemic pain occurs when tissue gets insufficient oxygen for its metabolic demand. Clinical examples include angina, intermittent claudication, and the intense pain accompanying sickle-cell anemia. Prior and current work from the McCleskey laboratory suggests that an acid-sensing ion channel, ASICS (also called DRASIC), may be a primary transducer of ischemic pain. Using genetically-altered mice, I hope to determine the role of this channel in ischemia-related muscle nociception. I have developed a new in vitro muscle-nerve preparation, which I will use in conjunction with patch clamp analysis of ion currents to examine ASICS current in response to specific ischemia-related stimuli. Most importantly, the new muscle-nerve preparation will allow me to determine whether ASICS responses are relevant in a physiological context. If successful, several important questions and paradoxes concerning ischemic pain will finally be answered. In addition, the experiments described in this proposal may validate a pharmaceutical target for the treatment of ischemic pain.