Seeing Pain: New approach to diagnosing and treating nerve damage | Chris McCurdy | TEDxUM

Translator: Reiko Bovee Reviewer: Denise RQ When I was a young child I lost my favorite uncle to alcohol abuse. It made me wonder why does this happen? How can someone be consumed by a substance that's around us all the time?

So, I made it my life's mission to become a drug expert, and I went to pharmacy school. I went to pharmacy school to understand what it is about drugs that can make us heal or can hurt us. When I was in pharmacy school, I found out I fell in love with the research.

Not only did I fall in love with the research I fell in love with this passion to educate others. And so, knowing that, I had to move forward. I had to move forward with my education so that I could carry those things out of my future; and I went on and earned a doctorate in medicinal chemistry; that's drug design not designer drugs.

(Laughter) That enabled me to move forward and really pursue some of the basis of drug abuse and addiction. Here I am now, a professor of medicinal chemistry and pharmacology. And I've dedicated my career to solving problems in drug abuse and actually finding better pain medications because after all, pain is the most common reason that individuals seek medical care.

It's also the most common reason that we end up with drug abuse and addiction. Moving from there, I've been able to establish a laboratory here, at the University of Mississippi, where we've done a lot of groundbreaking work - that I'll get to in a little bit - to move us forward in those endeavors. Now, how many people here have had to seek medical treatment that resulted in pain prescription?

Yes, most all of us. How many of you ended up getting something like morphine, or codeine, or Hydrocodone, or Oxycontin? Yeah.

Any of you had to take that for more than 2 or 3 weeks, maybe a month, maybe a couple? If so, there's a high likelihood your body became physically dependent. So why does that mean?

What do we mean when we talk about physical dependence and drug abuse? Let's define these things a little more clearly. So drug abuse is simply the concept that you take a drug out of the context that it was prescribed.

So, every now and then, all of us are guilty of taking a little more ibuprofen, or something, than it says on the bottle. That's drug abuse. If you've had to take chronic pain medications, particularly, opioid-based medications, over time, your body doesn't respond as effectively, and you have to increase the dose to relieve the pain.

That''s a phenomenon called tolerance. Tolerance: when it occurs, actually means that our body has become now physically changed and dependent on these outside medications. As we move forward and deeper into that, if we stop taking that medication abruptly, we go through withdrawal.

That withdrawal is actually physical dependence that defines that your body has become physically dependent. So it's not just the ones we think of as drug addicts on the street or hidden in their homes in suburbia. It could be any of us at any time.

There's never a prescription that tells who's going to head down that pathway. So, why is it in this day and age that we can't do a better job? Think about this.

If I was a physician, and you came to me with a broken bone, I could order an X-ray and I could easily see where the damage is. I want you to imagine what if we had the power to do that with a nerve that's been damaged. We don't have that ability.

So, treating pain is more or less a game of managing symptoms at this point. We can't tell where pain originates from. Oh, sure if you have a broken bone, that's probably where the pain is coming from.

But over 300 billion dollars is lost each year due to chronic pain, and lost workdays, and associated medical cost. If we could do a better job to see where that pain is coming from, we might be able to have a significant impact on society. It's also known that we lose about 62 billion dollars a year in people that are working in chronic pain just because of reduced job performance.

So, what about our treatment options for today? Why can't we do better? Well, modern medicine doesn't help; as much as we are in this age of medical revolution and getting towards personalized medicine, we still do a very lousy job at managing pain.

The drugs that are normally utilized, particularly for peripheral pain, and peripheral pain usually results in a numbness or tingling feeling, kind of like when your arm falls asleep, but it doesn't wake up, and it's chronic. It can be that simple to something that's so debilitating that you can't even function normally. So, the drugs that we used to treat this are not perfect; they cause drowsiness, they cause dizziness.

Drwsiness and dizziness sound like they would increase your ability to fall. If you are already in pain, or already hurting, that's a bad proposition. So, there's drugs like Neurontin and Lyrica, we've seen commercials for them on TV.

Those are mainstays of therapy for chronic pain, and when we move into those that are more in severe pain, we're looking at using opioid therapies. As we already discussed, opioids have their own problems. And so, with all of this concern, tolerance, abuse, addiction, we really need better ways to treat and better ways to diagnose.

So, where do we come in? Well, my laboratory has been involved for a number of years in targeting a protein called the Sigma protein. Sigma proteins are highly expressed on damaged nerve fibers.

We've been able to discover the most selective compounds for this protein in the world. We've patented those, and we've published those. That garnered us attention from researchers at Stanford University Medical Center, and they came to us with the proposition, "Could we turn this molecule that you've made into a radio-pharmatheutical that we could utilize in imaging the site of nerve damage?

" Through a lot of collaborative efforts, we were able to convert that molecule into a radio-pharmaceutical and start working using animal models of peripheral nerve damage. I won't go into the details because they get a little gory. However, we found out that we could pinpoint, using positron emission tomography and magnetic resonance imaging, the exact location of nerve damage.

You don't have to imagine this anymore. This is something that will be groundbreaking in the treatment of pain. To be able to accurately diagnose means that a physician could actually see where the pain is originating from, make surgical modifications to that area, or treat that area directly instead of having to use long-term chronic systemic drug therapy.

We're incredibly excited about this discovery. What's even more fascinating for us is the United States Food and Drg Administration recently gave us approval to move this into human clinical trials. We will be starting this in December at Stanford Medical Center.

The story takes another twist and turn, and it gets even better. Do you think, "Well, if you can revolutionize pain diagnosis, that's pretty good. " But a report appeared in the literature that showed compounds very similar to ours targeting the same protein actually have effects at reversing the pain.

So we said, "Wow, that's really cool. We took an injection of our molecule directly into a nerve-damaged site that we caused in an animal, reversed its pain for over two weeks; completely reversed its pain. Now, that's pretty exciting, but we're not going to do that in humans.

We're not going to go right into your damaged nerve and inject you. So, we have to find a drug that we can use systemically. So, we started to look at testing these in animal models of pain, and sure enough, our molecules were just as effective as drugs on the market that we use today for chronic pain: Neurontin, Lyrica, and even morphine.

That's all fine and dandy, but I already told you the current treatments are riddled with side effects and potential liabilities of addiction. So, immediately we want to see do our compounds cause the same types of problems? Do they cause animals to lose coordination and fall?

Do they cause sedation? They don't. Next, and most importantly, we wanted to know: are these molecules addictive?

So we tested these in several animal models of addition. Too elaborate to go into in detail, but what I can tell you is everything that we've seen so far shows absolutely no liability for abuse. This includes self-administration models where animals are trained to administer drugs directly into their brain.

They have no interest in our molecules. This is an exciting time. If we even take this one step further into a crazy place, but this is an idea where we won ahead; and that is now that we can visualize where the nerve is damaged, we can potentially treat the pain associated with that damage.

Stem cell research has now shown us that we can actually heal damaged nerves and get them to regenerate and reconnect, repair. How cool is this? Now we can show the physician where the damage is coming, and treat with stem cell therapy, wrap the nerve in a stent; that stent would be impregnated with our compound, that as that stent dissolves, the compound diffuses into the nerve fibers and eliminates the pain during the healing process.

We're incredibly excited about where we're headed. Someday, as the song by Morphine says, there may be a cure for the pain. We think we're well on our way.

Thank you very much.