Using Injectable Chilli Peppers To Reduce Pain

[Music] Medical breakthroughs, the research journey. [Music] Hello and welcome, I'm your host Caroline Verden, and you're about to join me on a journey into the fascinating world of medical breakthroughs, but not just any breakthroughs. We're diving into the personal stories, the setbacks, that you will not believe this moment, behind the cutting edge research happening right here at Leeds Teaching Hospitals NHS Trust. Coming up in this episode. We've finished the trial a while ago, the injectable chili pepper. Most people will be aware of they keep eating chilies, they can take more and more, so their nerves adjust to the the chili pepper, and people have been trying to do injectable forms to see if that helps reduce people's pain. No, you didn't miss here, using injectable chili peppers to reduce pain for arthritis sufferers. My name's Philip Conahan, and I'm Director of the NIHR Leeds Biomedical Research Centre. So I'm a rheumatologist by training, which is not a good name for a specialty, because nobody knows what it means, and it actually draws from an old Greek word meaning to flow, and it comes from the time of hypocrite, when people thought we had all these diseases in our bodies because of various evil humors and other things that flowed through us. So it's very interesting, but not a great name for a specialty. We deal with various joint and immune conditions, and for every medical specialty, there's a surgical specialty that's associated with it. So for rheumatologists, the surgical specialty is orthopedic surgeons, and I think they'll have more of an idea what orthopedic surgeons do, perhaps than what rheumatologists do. So rheumatologists do the non-surgical part of managing joint pain, and there's over a hundred conditions we deal with, but we generally try to break them up into two sorts of problems when I see somebody in clinic. I'm trying to work out whether they've got what I would call mechanical joint pain, problems that get worse the more you do. So the common problems there are tendon problems, often in our hands, and osteoarthritis, often in our fingers or large joints. And those sort of problems, those sort of mechanical problems, you wake up with 10 to 15 minutes of morning stiffness, or after you've been sitting for a long period of time, you're stiff getting up, I like watching people get up out of chairs at the cinema or on a bus or a tram, if you see them moving, you know what's going on. So typical mechanical problems, stiffness after disuse and worse pain as the day goes on and the more you do, the more pain you get. So that's the mechanical problems, and they make up probably 95% of joint problems. And then there's a smaller percentage, but if not more important because they're quite devastating to people of immune arthritis conditions, and that's like rheumatoid arthritis. So if osteoarthritis affects 10% of the population, rheumatoid arthritis only affects 1%, but it's a much more devastating disease that destroys joints. And in the last 20 years, we've really had a revolution in the treating of rheumatoid arthritis, and we've got very good drugs for treating that disease. It's an immune-based disease. We understand links to smoking and other things that trigger it, and we've got much better at treating it. So that's been a joy because I can tell you, 20, 25 years ago, rheumatoid was quite a depressing place to be with an absence of therapies at all. Included in those immune diseases, there's rheumatoid arthritis, the sort of arthritis that happens in about a third of the people who have the skin disease, psoriasis, called psoriatic arthritis. But as I say, small numbers of people are quite devastating to people. The mechanical problems, much more common, everybody in their life experiences back pain at some stage, osteoarthritis is something a lot of people will get as they get older. And tendon problems are amazingly common. And most of us get it, and it's all about being weak. So really affects a large number of the population? Yes, a huge number of people, and we know that about one in four GP consultations are related to, have an MSK component to them. A waskylose glitolaryne arthritis component. So this is really common stuff. And so there's a lot of work that is being done in leads at the moment. Looking at ways of improving outcomes, can you tell us a little bit about ads? We've got quite a range of researchers across different types of arthritis going on. So we've got people looking at the onset of rheumatoid arthritis and trying to predict it before it happens. And there are blood tests that we're trialing now that might be able to predict who's at risk over rheumatoid arthritis. We've got people looking at sorry at a cathritis. And again, trying to maybe look at people with bad psoriasis before they develop the joint problems. And what benefit could that have if you knew beforehand that you're at a risk? You save, he cool a lot of suffering, and you save the NHS a whole lot of work and cost. So it's got huge benefits for individuals and huge benefits for the health system. And prevention is something that the government cares about and has made open statements now that they want to move more from treating disease to preventing disease. So that's one strand of work that a couple of my colleagues are focusing on is trying to prevent those immune arthritis as starting. So does that mean that there is medication? So if you know that you're at a risk, there was actually something you can do to prevent it. There are things that can be done. And that's you can start to run one of our research groups now, Caroline, because what people do is first of all identify can we pick with reasonable certainly some sort of high risk group. And then you start to trial what you've got based on what we know about the how the disease works, you start to trial various drugs in that group of people. And this has been starting the last few years around the world. And leads is one of the world leaders in that group for pre rheumatoid arthritis for that condition. And they're doing various trials in that area and now to see if they can stop onset of disease. So as I say, that's one disease area we're working in. And then we work across a number of other disease areas. And my particular interest is in osteoarthritis and tendon problems because as I said, they're very common. We don't have any many drugs that help at all at present. The common therapies we use for common joint pains are a lantian flammatory drugs and most people will pop to an ibuprofen or an approximate at some stage in their life because you don't just use it for arthritis pain. It's used for headaches, it's used for period pain, it's used for a whole range of things. So but those drugs they help arthritis pain. But for many people they can't tolerate the pill. And I think patients sometimes feel guilty and it's just a side effect of the drug. And many people can't tolerate them. So we think about 60% or more people can't tolerate the drug or shouldn't be on it because those anti-inflammatory drugs can raise your blood pressure, put your risk of heart attacks, can cause stomach bleeding. It's all sorts of side effects. So we're pretty cautious about them. And apart from those drugs which come in rub on forms and pills, apart from those we don't really have a lot of stuff that works. Paracetamol doesn't work very well, opioids surprisingly don't work very well in the trials. And it's probably because opioids work centrally what we call in our brain. They don't work at the joint level where anti-inflammatories are working and where some of the new therapies might be working. So that comes to a big question which is where does pain come from in our joints? Yeah. And it would surprise many people to know that if we grab people off the street and started doing x-rays and MRI scans, we'd find a whole lot of problems in people's joints that had no symptoms. So there's a whole lot of structural problems in your joint in the joint lining cart legs that this sort of lining layer that protects the joint. There's a whole lot of problems with cart legion bone in most, in many people's joints, especially over the age of 40, 45. But mostly that don't have pain. So a big problem for my specialties has been working out where the pain comes from because that would make sensorous to then focus in and treat. And a lot of my work has been looking at that. Where we think Now. a lot of the pain comes from is not the sort of stuff you can see on an x-ray, but soft tissues. So around a joint is where two bones come together. At the end of the bone you've got this smooth white cartilage stuff, the same as the end of a chicken breast, that rubbery stuff that works as a shock absorber. Wrapped around the inside of every joint that nobody's ever heard of is a sin layer of cling wrap called the synovium and that lubricates your joints. In rheumatoid arthritis it's the synovium that gets inflamed and damages the joint. In osteoarthritis the cartilage and bone are damaged probably through minor injuries when we're young or major injuries when we've torn a ligament or something. But the pain is something different. So and there are many people with bad x-rays and no pain. And the answer to that lies that the things we don't see on an x-ray and often not on an MRI scan are the tendons and ligaments and where they attach to the joint. And we think that's where a lot of the pain comes from is where the ligaments and tendons are attaching onto the joint and helping keep your joint stable. So if you're weak you take a lot more strain through those areas around where the tendons and ligaments are attaching. And I'm a bit obsessed with getting people strong because everybody I've seen clinic can't undo a jar can't get out of a chair easily or can't get out of a car easily and they're all pretty good signs that you're weak. If you've not been able to get out of a chair without using your arms to push yourself up. If you had to stop having baths because you can't get out of a bath anymore that's a pretty good sign you've got weak leg muscles. Can't undo a jar you've got weak hand muscles and now the signs of being weak is is difficulty with doing buttons and you become clumsy and suddenly the kettle or full kettle becomes too hard for you to handle all those things are signs of weakness. Weak muscles which become tendons muscles become tendons stick onto joints. If you've got weak muscles you're going to take four to ten times more strain through your tendons suddenly you start to wake more suddenly you start to hurt when you walk up and downstairs because you don't have good leg muscle strength you're hurting on the steps. I think this is a familiar story to many people I talk to and the reason it happens is we get older is we tend often to get a little less active as we get older an academic site may spend a lot of time sitting in the office and putting on weight not staying a little bit active and staying strong. So one cause of joint pain one of the big causes of joint pain is probably the structures that surround the joint the tendons and where the tendons attach to bone and we and many other groups around the UK have done a lot of work on getting people strong and showing that it reduces pain very substantially as much as a pill would do. That's extraordinary that actually it's reversible at no cost really you don't need to join a gym to get strong you can do many things around the house and just out and about that that's so lovely it takes some time and taking a pill takes 10 seconds and often what I'm asking people to do takes 30 minutes a day and that's hard because most of us have busy lives you know kids work family everything takes their time so I think one of the key things for life is cutting off some time to look after yourself and that's a really hard thing for lots of people because I've got so many care or responsibilities and other things in their lives. Yeah I suppose it's very easy to say isn't it just 30 minutes a day you know you've got you know 24 hours you come on you can find that but actually when you put it like that it everyone is fighting different battles aren't we? And the other thing is first that I like to do it in a sort of structured way my motto is first get strong then get fit and people come to me who can't do a straight leg raise with their leg they don't realize till you examine them but you can tell watching them get out of a chair that they've got weak leg muscles and if you're weak then you can't be fit you cannot be fit because you can't work walk and they're aerobic rate you can't do things so I think just telling weak people to go for a walk every day it's probably not a good thing to start with first let's get you strong and an a simple thing everybody can do is walking laps in a swimming pool just in the shallow end walking 30 or 40 widths of a pool that feeling of pushing against resistance is a good starter exercise to start getting you strong there's we need more pools in lades I think we need more access to pools it's not cheap for some people to get access but at least now there's women's only sessions and there's a few more variety for things for people to be able to get there to do stuff but I do know it's a cost burden on some people to be able to access that so that's one way of building leg muscles and for hand muscles just putting a cushion on your lap when you watch TV so you're resting your forearms putting a squeeze ball or a soccer man sock rolled in a ball in one hand and squeezing until your arm drops off then putting it in the other hand back and forth 30 times each arm that's a great way of getting strong so it's not an on and off motion it's not which will make you worse it's a sustained squeeze while resting your forearm and that will reverse most people's grip strength problems and reduce their hand pain a lot for osteoarthritis the best thing we can do in the community now is get everybody strong and then I'd have 50% less patience in clinic turning our teeth with joint pain if we could get most people strong you think it would have a big up bigger effect I think yeah the trials suggest big effects if you have trouble under your jar if you're difficulty getting out of a chair you've got a problem that needs addressing even if it's not even if you've got no pain do it now get stronger now but it's really hard to stay strong all your life and maybe such therapies are never going to work well in people who roll though who can't do things so we are going to need drug therapies one of our research projects we're running at Leeds at Presum is indeed an online program we've developed a digital intervention that you can use on the computer or on your phone called DMAP and we're just going into human trials now we're just doing trials with large numbers of people now for anybody with hand pain, wrist pain or elbow pain because they're all connected all use the same muscles and we're running this program now to see it's taken a lot of development with patients we've worked together with patients which is the modern way we do research we come up with a question we take it to a group of patients and say is this a good question do you care about this then we work with them to co-design what an intervention would look like and in this case we had a lot of input in what people wanted and so now we've got a trial and see if it works and the problem for modern medicine and the problem for the days of an internet that's so open is there so much false knowledge false evidence out there that really is harmful to people who have pain and suffering and fatigue and all the things that go with pain who end up often spending money on a lot of things that are just a waste of time and that to me is a real that's the downside modern times isn't internet is a huge force for good in spreading information and communication but the downside is all the missing information and lies that are out there and at the end of those lies is often somebody making some bugs so you've got to watch for that so this research obviously you can see how it has the potential to impact a huge number of people because you're talking about doing relatively simple things at relatively low costs what's the importance of all of this research sort of globally not just for us here in Leeds so Leeds in the arthritis field has been a big international leader in a number of areas in rheumatoid arthritis and sorry adic arthritis and in osteoarthritis the things we do we often collaborate with other centres around the UK in our trials and interventions and we've got a network of colleagues around the country that we do things with and we all are part of international guidelines and so I think there's the coming up with new therapies piece of work that's that's one strand of what we do, there's some of that involves drug trials, which involves patients. There's international guidelines for how we treat things that influence thousands and thousands of doctors across Europe and the world, and we've been part of many of those guidelines. And those modern treatment guidelines are all based on basically trials. It's saying, you know, with the trials of drug effective, no, it doesn't get in, you know, it didn't work. And that's what we want. We want a real evidence synthesis. So if the research done here, does percolate up nationally, does percolate internationally, and we've got good evidence for a lot of that. Now, I've mentioned getting strong. The other part of work we do is looking at drugs. So I mentioned we don't have many drugs for the pain of osteoarthritis. And one of our other areas is trying to look at new drugs that are coming along and seeing if they work. And it's not a small business. It takes even a small trial, a sort of first early trial of a new therapy might need 50 to 100 patients followed over three to six months, sometimes after two years. So it's a lot of work and the cost of those trials when we're riding grant, monies for these trials can cost two to three million pounds to do one of those studies. So that's why we're not doing lots and lots of trials. There's a limitation in in bucks and what we can do. But we've worked with industry, with companies that are developing new products and want to put them through the rigor of a proper valuable trial. And the recent ones we've looked at were still waiting. We finished a trial a while ago of an injectable chili pepper. If you like something that most people will be aware of, they keep eating chilies, they can take more and more. So their nerves adjust to the the chili pepper and people have been trying to do injectable forms to see if that helps reduce people's pain. And we're waiting on results of trials. The trials are finished. We're waiting on results to see if those trials are going to be effective. And they may only work short term, which won't help people. What's the link between the pepper and the stopping of the pain? Okay, so pain arises from nerves and it arises from the nerves. I've said the tissues that are involved, the sort of tendons and where they attach to the joint. But at those points you've got lots of nerves, what we call not succettive nerves, the nerves that conduct pain signals. And what the chili pepper does is affects a molecule called TRPV1. So these molecules make the nerves shrink a little bit, temporarily shrink. And that's what's happening when you're eating lots of chilies is you're desensitizing your tongue nerves. And that's what we're the same thing we're trying to do inside the joint. Now, as well at the end of the nerve, there's not just the TRPV that I just mentioned, receptors, there's other little molecules that are conducting pain signals. And probably the most exciting thing we've been involved with recently is a new drug that modulates another nerve pain conductor called NIRATROFIN3. And we've shown that a drug that mobs up NIRATROFIN3 dramatically reduces people's knee pain. And we've presented that trial, we've got the results of that trial and was very positive. And we presented that at the American College of Rheumatology meeting last year. And now the company that's involved with that, which is a small UK startup company, is looking to raise funds to do a much bigger trial. I think one more big trial could be could see that get through to humans in the next four years or so. So that's on the cards, but it's about raising money to do the trials. And that's the sort of business side of things that we're not involved with. That's outside of us, but we try our best to be ready to do the trial when it comes along. That must be quite. That must be quite frustrating for I imagine for you, because you do a small trial, you see it success and you think, gosh, it's going to be amazing for my patients, but then there's just not enough money for these other businesses to then go and find the funding in order to do these bigger trials. And for that to then become a normalised procedure. An osteoarthritis, although it's incredibly common, has not been so sexy for big farmer to look at. Because there's been a whole lot of drugs tried and failed. And therefore, they really want to be risk averse in that area. But there is always an interplay in our world of business versus health care. And so sometimes you wish things could move quicker. We also did a positive trial a few years ago, over a common drug used for rheumatoid arthritis called meat that treksate. And we did trial and osteoarthritis that showed that indeed it did reduce the pain of osteoarthritis. And we're still working out how to make that because it's a drug that it has some side effects, about 70% of people can stay on it, but 30% can't. It needs monitoring with blood tests over time. And before I can say to all the GP's you should be using this drug. We think we've probably got to find the group of patients who will get most benefit. So we sort of restrict the numbers of patients and make it more feasible for primary care to be able to use that drug. So there's the drug where we've got preliminary evidence from a large trial that it works, but it's how to make it fit into clinical practice. So now you're starting to see the spectrum that research is involved with. There's non-drug therapies, there's drug therapies, there's getting things through trials. And then there's getting them into the routine practice. If I've got a great drug, but it's really hard to monitor and it takes a lot of work, that's no good for a primary care system that's already overwhelmed and barely coping with what they've got to see now. So all those things come into what we weigh up. There's so many components to this. Before you you actually end up as a patient with a drug or a body of physio work that you can do and take on, there's so many different components in so many years. It's its own game and you've got to understand it. And luckily now we've got a lot of patients who've been involved who do understand and they help path, you know, agrees the tracks for other patients to come in and understand the processes and things. But yeah, it takes a long time to get things done. You have to be patient, somewhat to be a researcher or bit crazy, both those things help. And if you'd like to find out more about anything you've heard about in today's episode, just check out the show notes. Coming up on our next episode, the AI algorithm is called Find AF. It was developed by ourselves at the University of Leeds. We developed and checked two million people in the UK. We've now done that in 9 million people in other countries. So this algorithm could go much further internationally globally and it could actually be something that we export. Can an algorithm predict a stroke could lead to be changing the face of worldwide healthcare? That's all coming up in our next episode. Medical breakthroughs, the The Research Genie is an under the mast audio production.