Sodium channels and pain

Published on January 26, 2009   40 min

Other Talks in the Category: Biochemistry

My name is Steve Waxman. I work at Yale University, and one of my major interests is the role of sodium channels and other ion channels in neuropathic pain.
This slide shows a case history from an individual with neuropathic pain. It represents a significant unmet medical need in the United States, and in every nation. Tommy was a highly decorated police officer. He had received a number of commendations for his work, an absolutely exemplary worker. And then, he sustained a gunshot wound, which injured his radial nerve. He was left with sensory loss in a motor deficit, but what debilitated him was severe neuropathic pain. As you can see from this slide, he didn't respond or responded minimally, to a large number of medications. He had some relief, but it was only partial, with carbamazepine, a lidocaine patch, they're both sodium channel blockers, and with opiates. And Tommy is followed by a consortium of a neurologist, a pain specialist, and a psychiatrist. But he remains disabled, unable to work because of his neuropathic pain. And so it's incumbent on us to understand neuropathic pain, and to develop new, more effective medications. As I said, this is a significant unmet medical need.
Now, this slide appears in virtually every textbook of physiology. This is the Hodgkin-Huxley mechanism of action potential, electrogenesis, or nerve impulse electrogenesis. This is work that they did in the 1952, studying the giant axon of the squid, and what they show is that the upstroke, the depolarizing phase of the nerve impulse, the action potential, it's upstroke depends on the opening up of sodium channels. That's shown in yellow on this slide. And in this work, which they did many decades ago, even though they didn't have modern computers, and molecular biology was in its infancy, patch clamping didn't exist, even though they worked with very primitive tools by our current standards, they were able to predict the presence of sodium channels. They couldn't see the channels. They didn't know the molecular structure of the channels. But they were able to predict many of their properties. And this work, the Hodgkin-Huxley formulation of nerve impulse generation, remains one of the bastions of modern neurophysiology. And it underscores the crucial importance of sodium channels for neuronal signaling.