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0:00
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.
0:13
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.
1:24
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.
