June 25, 2025 • 28 mins
Arthritis affects millions—but there’s hope. Professor Phil Conaghan shares some of the research that’s being done in Leeds into reducing pain- which includes the use of chilli peppers. He also shares how to keep your joints healthy, avoid knee pain, and improve your quality of life through early care and innovation.
Views and experiences shared in this podcast belong to the individuals and do not constitute medical advice. For medical advice please contact your pharmacist, GP or dial 111. In an emergency please dial 999.
This podcast was recorded and produced by Under the Mast– creative audio productions and was presented by Caroline Verdon
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:07):
Medical breakthroughs,the research journey.
Hello and welcome.
I'm your host, Caroline Burden,and you are about to join me on
a journey into the fascinatingworld of medical breakthroughs,
but not just any breakthroughs.
We are diving into thepersonal stories, the setbacks.
(00:30):
That you will not believe thismoment behind the cutting edge
research happening right here atLeeds Teaching Hospitals NHS Trust.
Coming up in this episode,
we finished a trial a while agoof an injectable chili pepper.
Most people will be aware if theykeep eating chilies, they can take
more and more, so their nervesadjust to the the chili pepper.
(00:53):
And people have been trying todo injectable forms to see if
that helps reduce people's pain.
No, you didn't miss here, usinginjectable chili peppers to reduce
pain for arthritis sufferers.
My name's Philip Conaghan andI'm director of the NIHR leads
Biomedical Research Center.
So I'm a rheumatologist by training,which is not a good name for a
(01:18):
specialty because nobody knows what itmeans, and it actually draws from an
old Greek word meaning to flow from.
At the time of Hippocrates when peoplethought we had all these diseases in our
bodies because of various evil humorsand other things that flowed through us.
So, um, it's very interesting, butnot a great name for a specialty.
(01:42):
We deal with various jointand immune conditions.
And for every medical specialty,there's a surgical specialty
that's associated with it.
So for rheumatologists, the surgicalspecialty is orthopedic surgeons
and people have more of an ideawhat orthopedic surgeons do perhaps
than what rheumatologists do.
(02:02):
So rheumatologists do the non-surgicalpart of managing joint pain, and there's
over a hundred conditions we deal with.
Um, but we generally try to breakthem up into two sorts of problems.
When I see somebody in clinic, I'mtrying to work out whether they've got
what I would call mechanical joint painproblems that get worse the more you do.
(02:27):
So, uh, that common problems.
There are tendon problems often inour hands and osteoarthritis, often
in our fingers or large joints.
And those sort of problems, those sort ofmechanical problems, you wake up with 10
to 15 minutes of morning stiffness, uh,or after you've been sitting for a long
(02:48):
period of time, you're stiff getting up.
I like watching people get up outof chairs at the cinema or on a
bus or a tram if you see them, um,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.
(03:10):
So that's the mechanical problems.
And they make up probably95% of of joint problems.
And then there's a smallerpercentage, but, um.
If not more important becausethey're quite devastating to people
of immune arthritis conditions, andthat's like rheumatoid arthritis.
So if osteoarthritis affects 10% ofthe population, rheumatoid arthritis
(03:34):
only affects 1%, but it's a much moredevastating disease that destroys joints.
In the last 20 years, we've reallyhad a revolution in the treating of
rheumatoid arthritis, and we've got verygood drugs for treating that disease.
It's an immune-based disease.
We understand links to smokingand other things that trigger it.
(03:57):
We've got much better at treating it.
So that's been a joy because I cantell you 20, 25 years ago, rheumatology
was quite a depressing place to be.
With an absence of, of therapies atall included in those immune diseases,
there's rheumatoid arthritis, thesort of arthritis that happens in
about a third of the people whohad the skin disease, psoriasis.
(04:18):
Psoriatic arthritis.
Um, but as I say, small numbers ofpeople are quite devastating to people.
The mechanical problems much more common.
Everybody in their life experiencesback pain at some stage.
Osteoarthritis is something a lot ofpeople will get as they get older, and
tendon problems are amazingly common.
(04:41):
Um, and, and most of us get it,and it's all about being weak.
So it really affects a largenumber of the population.
Yes.
Um, a huge number of people andwe know that about one in four
GP consultations are related tohave an MSK component to them.
(05:03):
Wow.
A musculoskeletal oran arthritis component.
So, um, this is really common stuff.
And so there's a lot of work, uh, thatis being done in leads at the moment,
looking at ways of improving outcomes.
Can you tell us a little bit about that?
Um, we've got quite a, a range ofresearchers across different types
(05:26):
of arthritis going on, so we'vegot people looking at the onset
of rheumatoid arthritis and tryingto predict it before it happens.
And there are blood tests thatwe're, we're trialing now that
might be able to predict who'sat risk of rheumatoid arthritis.
We've got people looking atpsoriatic arthritis and again.
Trying to maybe look at peoplewith bad psoriasis before they
(05:50):
develop the joint problems.
And what benefit could thathave if you know beforehand
that you're, you are at a risk,
you save people a lot of suffering and yousave the NHSA whole lot of work and cost.
So it's got huge benefits for individualsand huge benefits for the health system.
And prevention is something that,um, the government cares about and
(06:13):
has made open statements now thatthey wanna move more from treating
disease to preventing disease.
So that's one strand of work thata couple of my colleagues are
focusing on is, is trying to preventthose immune arthritises starting.
So does that mean thenthat there is medication?
So if you know that you're at arisk, there is actually something
you can do to prevent it.
(06:34):
There.
There are things that can be done
and that's, you can start to runone of our research groups now,
Caroline, because that what peopledo is first of all identify, can we.
Pick with reasonable certainty, somesort of high risk group, and then
you start to trial what you've got.
Based on what we know about the howthe disease works, you start to trial
(06:57):
various drugs in that group of people.
And this has been starting the last fewyears round 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 trialsin that area now to see if
they can stop onset of disease.
So as I say, that's onedisease area we're working in.
(07:20):
And then we work across anumber of other disease areas.
And my particular interest is inosteoarthritis and tendon problems
because as I said, they're very common.
We don't have any many drugsthat help at all at present.
Um, the common therapies we use for,um, uh, common joint pains are oral,
(07:44):
anti-inflammatory drugs, and mostpeople will pop an ibuprofen or.
Naproxen at some stage in their life.
'cause you don't just useit for arthritis pain.
It's used for headaches,it's used superior pain.
It's used for a whole range of things.
So, uh, but those drugs, theyhelp arthritis pain, but.
(08:05):
For mo, for many people, they can'ttolerate the pill and, and I think
patients sometimes feel guilty andit's just a, a side effect of the drug
and many people can't tolerate 'em.
So we think about 60% or more people can'ttolerate the drug or shouldn't be on it
because those anti-inflammatory drugs canraise your blood pressure, put you at risk
(08:27):
of heart attacks, can stomach bleeding.
There's all sorts of side effects, so.
We're pretty cautious about themand 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 verywell in the trial, in the trials, and
(08:51):
it's probably because opioids workcentrally what we call in our brain.
They don't work at the joint levelwhere, where anti-inflammatories
are working and where some of the.
Uh, new therapies might be working.
So that comes to a big question, which iswhere does pain come from in our joints?
Yeah.
(09:11):
And it would surprise manypeople to know that if we.
Grab people off the street andstarted doing x-rays and MRI scans,
we'd find a whole lot of problems inpeople's joints that have no symptoms.
So there's a whole lot of structuralproblems in your joint, in the joint
lining cartilage, the, the sort oflining layer that protects the joint.
(09:34):
There's a whole lot of problemswith cartilage and bone in
most, in many people's joints,especially over the age of 40, 45.
Um, but mostly they don't have pain.
So a big problem for my specialties hasbeen working out where the pain comes
from because that would make sensefor us to then focus in and treat.
And, and a lot of my work has beenlooking at that, where we think now
(09:59):
that a lot of the pain comes fromis not the sort of stuff you can
see on an x-ray, but soft tissues.
So around a joint is wheretwo bones come together.
At the end of the bone, you've gotthis smooth white cartilage stuff the
same as the end of a chicken breast.
That rubbery stuff that works as a shockabsorber wrapped around the inside of
(10:21):
every joint that nobody's ever heardof is a thin layer of cl wrap called
the synovium, and that lubricates yourjoints in rheumatoid arthritis, it's
the synovium that gets inflamed anddamages the joint in osteoarthritis.
The cartilage and bone are damagedprobably through minor injuries when
(10:43):
we're young, or major injuries whenwe've torn a ligament or something.
Um, but the pain is something different.
Um, so, and there are many peoplewith bad x-rays and no pain.
And the answer to that lies thatthe things we don't see on an
X-ray and often not on an MRI scanare the tendons and ligaments and
(11:04):
where they attach to the joint.
And we think that's where a lotof the pain comes from, is where
the ligaments and tendons areattaching onto the joint and, and
how helping keep your joint stable.
So if you are weak.
You take a lot more strain throughthose areas around where the tendons
(11:24):
and ligaments are attaching, and I'ma bit obsessed with getting people
strong because everybody I see in cliniccan't undo a jar, can't get out of a
chair easily, or can't get out of acar easily, and they're all pretty good
signs that you are weak if you've notbeen able to get out of a chair without
(11:45):
using your arms to push yourself up.
If you had to stop having bathsbecause you can't get out of the bath
anymore, that's a pretty good sign.
You've got weak leg muscles,um, can't undo a jar.
You've got weak hand muscles.
And the other signs of being weakis, is difficulty with, uh, doing
(12:07):
buttons and you become clumsy andsuddenly the kettle, a 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'regonna take four to 10 times more
strain through your tendons.
Suddenly you start to wake more,suddenly you start to hurt when you
(12:31):
walk up and down stairs because youdon't have good leg muscle strength,
you are hurting on the steps.
Um, I think this is a familiarstory to many people I talk to,
and the reason it happens is weget older is we tend often to get a
little less active as we get older.
And academics, like me spend alot of time sitting in the office
(12:53):
and putting on weight, not.
Staying a little bitactive and staying strong.
So one cause of joint pain.
One of the big causes of joint painis probably the structures that
surround the joint, the tendons, andwhere the tendons attached to bow.
And we and many other groups aroundthe UK have done a lot of work on
(13:14):
getting people stroll and showing thatit reduces pain very substantially,
as much as a pill would do.
That's extraordinary, that actuallyit's reversible at, at no cost really.
You don't need to joina gym to get strong.
You can do many things around thehouse and, um, just out and about.
Um, that
absolutely extraordinary.
(13:35):
And it takes, it takes some time.
And, and taking a pill takes 10 seconds.
Yeah.
Um, and often what I'm askingpeople to do takes 30 minutes.
A day.
And that's hard becausemost of us have busy lives.
You know, kids work, family,everything takes their time.
(13:57):
So, uh, I think one of the keythings for life is, is cutting off
some time to look after yourself.
And that's a really hard thingfor lots of people 'cause they've
got so many carer responsibilitiesand other things in their lives.
I suppose it's very easy to say,isn't it just 30 minutes a day?
You know, you've got, youknow, 24 hours you come on.
(14:20):
You can find that.
But actually when you put it likethat, it, it, everyone is, uh, is
fighting different battles, aren't we?
And the other thing is, first that I liketo do it in a sort of structured way.
My motto is, first, getstrong, then get fit.
People come to me who can't do astraight leg raise with their leg.
(14:40):
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 um, if you're weak,then you can't be fit.
You cannot be fit because youcan't work, walk and aerobic rate.
You can't do things.
So I think just telling weak peopleto go for a walk every day, it's
(15:03):
probably not a good thing to start with.
First, let's get you strong and,and a simple thing everybody can
do is walking laps in a swimmingpool, just in the shallow end.
Walking 30 or 40 widths of the foot ofa pool, that feeling of pushing against
resistance, um, is a good starterexercise to start getting you strong.
(15:25):
And there's, we need more pools in leads.
I think we need more access to pools.
It's not cheap for some people to getaccess, but at least now there's women's
only sessions and there's a few morevariety for things, for people stuff.
But I, I do know it's a.
(15:45):
To be able to, to access that.
So that's one way ofbuilding lead muscles.
Um, and for hand muscles, uh, just puttinga cushion on your lap when you watch tv.
So you're resting your forearms, puttinga squeeze ball or a sock, a man's
sock rolled in a ball in one hand, andsqueezing until your arm drops off.
(16:08):
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 squeezewhile resting your forearm.
And that will reverse mostpeople's grip strength problems
(16:28):
and reduce their hand pain a lot.
For osteoarthritis.
The best thing we can do in the communitynow is get everybody strong and then
I'd have 50% less patients in clinicturning up with, with joint pain.
If we could get most people strong.
You think it would havethat gut pick effect?
I think, yeah.
(16:48):
The, the trials suggest big effects.
If you have trouble in doing a jar, if youhave difficulty getting out of a chair.
You've got a problem that needsaddressing, 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 strongall your life and maybe such therapies
are never going to work well in peoplewho are older who can't do things.
(17:12):
So we are gonna need drug therapies.
One of our research projects we're runningat Leeds at present is indeed an an online
program we've developed, uh, at digitalintervention that you can use on the
computer or on your phone, um, called D.
We're just going into human trials now.
(17:33):
We're just doing trials with largenumbers of people now, for anybody with
hand pain, wrist pain, or elbow painbecause they're all connected, all use
the same muscles, and we're runningthis program now to see It's taken
a lot of development with patients.
We've worked together withpatients, which is the modern way.
We do research.
(17:53):
We.
Come up with a question, we takeit to a group of patients and
say, is this a good question?
Do you care about this?
Then we work with them to co-designwhat an intervention would look like.
And in this case, we had a lotof input in what people wanted.
Um, and so now we've gottatrial it and see if it works.
(18:13):
And the problem for modern medicine andthe problem for the days of an internet
that's so open is there's so much false.
Knowledge, false evidence out there thatreally is harmful to people who have
pain and suffering and fatigue and allthe things that go with pain, um, who
end up often spending money on a lot ofthings that are just a waste of time.
(18:37):
And that, to me is a real, that's thedownside of modern times, isn't it?
Internet is a huge force for good in, inspreading information and communication.
But the downside is all themisinformation and lies that are out
there, and at the end of those liesis often somebody making some bucks.
Um, so you've gotta watch for that.
(18:59):
So this research, obviously you cansee how it has the potential to impact
a huge number of people because you'retalking about doing relatively simple
things, um, at relatively low costs.
What's the importance of, of, of allof this research sort of globally,
(19:21):
not just for us here in Leeds.
So, um, leads in the arthritis fieldhas been, um, a big international
leader in a number of areas, um, inrheumatoid arthritis, in psoriatic
arthritis, and in osteoarthritis.
The the things we do, we often collaboratewith other centers around the UK in our
(19:43):
trials and interventions, and we've got a.
We all are part of internationalguidelines, and so I think
there's the coming up with newtherapies piece of work, that's,
that's one strand of what we do.
There's some of that involves drugtrials, which involves patients.
(20:06):
There's international guidelines for howwe, uh, treat things that that influence.
Thousands and thousands of doctors acrossEurope and and the world, and we've
been part of many of those guidelinesand those modern treatment guidelines
are all based on basically trials.
It, it's saying, you know, wasthe trials of Drug X effective?
(20:29):
No, it doesn't get in.
You know, it, it didn't work.
And, and that's what we want.
We want a real evidence synthesis.
So the research done heredoes percolate up nationally.
Does percolate internationally.
Um, and we've got goodevidence for a lot of that.
Now I've mentioned getting strong.
(20:51):
The other part of work wedo is, is looking at drugs.
So I've mentioned we don't have manydrugs for the pain of osteoarthritis.
And one of our other areas is, is tryingto, um, look at new drugs that are
coming along and seeing if they work.
And it's not a small business, it takes.
Uh, even a small trial, a sort offirst early trial of, um, a new
(21:16):
therapy might need 50 to a hundredpatients followed over three to six
months, sometimes out to two years.
Um, so it's a lot of work and the costof those trials when we're riding grant
monies for these trials can cost two to 3million pounds to do one of those studies.
So that's why we're not doinglots and lots of trials.
(21:40):
There's a limitation in,in and what we can do.
Um, but we've worked with industry,with companies that are developing
new products and want put them throughthe rigor of, of a proper trial and.
Um, the recent ones we'velooked at, we're still waiting.
(22:00):
We finished a trial a while ago ofa, an injectable chili pepper, if you
like, something that most people willbe aware if they keep eating chilies,
they can take more and more, so theirnerves adjust to the, the chili pepper.
And people have been tryingto do injectable forms.
That reduce people's pain andwe waiting on results of trials.
(22:21):
Trials finished.
We're waiting on results to see ifthose trials are gonna be effective,
may work short term, which won't.
What's the link between the pepperand the, the stopping of the pain?
Okay, so pain arises from nervesand it arises from the nerves.
I've, I've said the tissues that areinvolved, the sort of, um, tendons
(22:44):
and where they attach to the joint.
But at those points you've got lots ofnerves, what we call nociceptive nerves,
the nerves that conduct pain signals.
And what the chili pepper does isaffects a molecule called tr trp V one.
So these molecules, um,make the, the nerve shrink a
(23:05):
little bit temporarily shrink.
And that's what's happening when you'reuse eating lots of chilies is you're,
you are desensitizing your tongue nerves.
And that's what we're the same thingwe're trying to do inside the joint.
Now as well at the, at the end ofthe nerve, there's not just the T RRP
(23:28):
V that I just mentioned, receptors.
There's other little re uh, moleculesthat are conducting pain signals.
And probably the most exciting thingwe've been involved with recently is, uh,
a new drug that modulates another nerve.
Um, pain conductor calledin Neurotrophin three.
(23:50):
We've shown that that a drug that mopsup Neurotrophin three dramatically
reduces people's knee pain.
And we've presented that trial,we've got the results of that
trial and was very positive.
Um, and we presented that at the AmericanCollege of Rheumatology meeting last year.
(24:10):
And now the company that's involved withthat, which is a small UK startup company.
Um, is looking to raise fundsto do a much bigger trial.
I, I think one more big trial couldbe, could see that get through to
humans in the next four years or so.
So that's on the cards, but it's aboutraising money to do the trials and
(24:33):
that's the sort of business side ofthings that we are not involved with.
That's that's outside of us, butwe try our best to, to be ready to
do the trial when it comes along.
That must be quite,
that's gonna be important.
That must be quite frustrating for,I, I imagine for you because you,
you, you do a smaller trial, you seeits success and you think, gosh, this
(24:55):
could be amazing for my patients.
But then there's, there's just notenough money for these other businesses
to then go and find the funding inorder to do these bigger trials.
And for that to then, you know,become a, a, a normalized procedure.
An osteoarthritis, although it'sincredibly common, has not been
so sexy for big pharma to look at.
Yeah, and that's because there's beena whole lot of drugs tried and failed
(25:18):
and therefore people really want tobe risk averse in that area, but, but
there is always an interplay in our.
World of business versus, um, youknow, health, healthcare and, um, yeah.
So sometimes you wishthings could move quicker.
We also did a positive trial a fewyears ago of a common drug use for
(25:40):
rheumatoid arthritis called methotrexate.
And we did a trial in osteoarthritisthat showed that indeed it did reduce
the pain of osteoarthritis and.
We're still working out how tomake that, uh, because it's a drug
that it has some side effects.
About 70% of people canstay on it, but 30% can't.
(26:02):
It needs monitoring withblood tests over time.
And before I can say to all the gps,you should be using this drug, we
think we've probably gotta find the.
Patients who will get most benefit.
So we sort of restrict the numbersof patients, um, and make it
more feasible for primary careto be able to use that drug.
(26:24):
So there's another drug where we'vegot preliminary evidence from a large
trial that it works, but it's how tomake it fit into clinical practice.
So I think now you'restarting to see the spectrum.
Research is involved with, there'snon-drug therapies, there's drug
therapies, there's getting things throughtrials, and then there's getting them
(26:47):
into the routine practice if I've got agreat drug, but it's really, you know,
hard to monitor and it takes a lot of workthat's no good for a primary care system
that's already overwhelmed and barelycoping with what they've got to see now.
So all those things comeinto what we weigh up.
(27:09):
There's, there are somany components to this.
Before you, you actually end up as apatient with a drug or a body of physio
work that you can do and take on.
There's so many differentcomponents and so many years,
it's its own game andyou've gotta understand it.
And luckily now we've got a lot ofpatients who've been involved who
do understand and they help path,uh, you know, grease the tracks for
(27:33):
other patients to come in and, andunderstand the processes and things.
But yeah, it takes a longtime to get things done.
You have to be patient somewhatto be a researcher or big, crazy.
Both of those things help.
And if you'd like to find out moreabout anything you've heard about in
today's episode, just check out the shownotes coming up on our next episode.
(27:54):
The AI algorithm is called FIND af.
It was developed by ourselvesat the University of Leeds.
We developed and checked 2million people in the uk.
We've now done that in 9 millionpeople in other countries, so this
algorithm could go much further.
Internationally, globally, and it canactually be something that we export,
can an algorithm predict a strokecould lead to be changing the
(28:17):
face of worldwide healthcare.
That's all coming up in our next episode.
Medical Breakthroughs.
The research journey is anunder the mask audio production.
Medical breakthroughs,the research journey.
Hello and welcome.
I'm your host, Caroline Burden,and you are about to join me on
a journey into the fascinatingworld of medical breakthroughs,
but not just any breakthroughs.
We are diving into thepersonal stories, the setbacks.
(00:30):
That you will not believe thismoment behind the cutting edge
research happening right here atLeeds Teaching Hospitals NHS Trust.
Coming up in this episode,
we finished a trial a while agoof an injectable chili pepper.
Most people will be aware if theykeep eating chilies, they can take
more and more, so their nervesadjust to the the chili pepper.
(00:53):
And people have been trying todo injectable forms to see if
that helps reduce people's pain.
No, you didn't miss here, usinginjectable chili peppers to reduce
pain for arthritis sufferers.
My name's Philip Conaghan andI'm director of the NIHR leads
Biomedical Research Center.
So I'm a rheumatologist by training,which is not a good name for a
(01:18):
specialty because nobody knows what itmeans, and it actually draws from an
old Greek word meaning to flow from.
At the time of Hippocrates when peoplethought we had all these diseases in our
bodies because of various evil humorsand other things that flowed through us.
So, um, it's very interesting, butnot a great name for a specialty.
(01:42):
We deal with various jointand immune conditions.
And for every medical specialty,there's a surgical specialty
that's associated with it.
So for rheumatologists, the surgicalspecialty is orthopedic surgeons
and people have more of an ideawhat orthopedic surgeons do perhaps
than what rheumatologists do.
(02:02):
So rheumatologists do the non-surgicalpart of managing joint pain, and there's
over a hundred conditions we deal with.
Um, but we generally try to breakthem up into two sorts of problems.
When I see somebody in clinic, I'mtrying to work out whether they've got
what I would call mechanical joint painproblems that get worse the more you do.
(02:27):
So, uh, that common problems.
There are tendon problems often inour hands and osteoarthritis, often
in our fingers or large joints.
And those sort of problems, those sort ofmechanical problems, you wake up with 10
to 15 minutes of morning stiffness, uh,or after you've been sitting for a long
(02:48):
period of time, you're stiff getting up.
I like watching people get up outof chairs at the cinema or on a
bus or a tram if you see them, um,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.
(03:10):
So that's the mechanical problems.
And they make up probably95% of of joint problems.
And then there's a smallerpercentage, but, um.
If not more important becausethey're quite devastating to people
of immune arthritis conditions, andthat's like rheumatoid arthritis.
So if osteoarthritis affects 10% ofthe population, rheumatoid arthritis
(03:34):
only affects 1%, but it's a much moredevastating disease that destroys joints.
In the last 20 years, we've reallyhad a revolution in the treating of
rheumatoid arthritis, and we've got verygood drugs for treating that disease.
It's an immune-based disease.
We understand links to smokingand other things that trigger it.
(03:57):
We've got much better at treating it.
So that's been a joy because I cantell you 20, 25 years ago, rheumatology
was quite a depressing place to be.
With an absence of, of therapies atall included in those immune diseases,
there's rheumatoid arthritis, thesort of arthritis that happens in
about a third of the people whohad the skin disease, psoriasis.
(04:18):
Psoriatic arthritis.
Um, but as I say, small numbers ofpeople are quite devastating to people.
The mechanical problems much more common.
Everybody in their life experiencesback pain at some stage.
Osteoarthritis is something a lot ofpeople will get as they get older, and
tendon problems are amazingly common.
(04:41):
Um, and, and most of us get it,and it's all about being weak.
So it really affects a largenumber of the population.
Yes.
Um, a huge number of people andwe know that about one in four
GP consultations are related tohave an MSK component to them.
(05:03):
Wow.
A musculoskeletal oran arthritis component.
So, um, this is really common stuff.
And so there's a lot of work, uh, thatis being done in leads at the moment,
looking at ways of improving outcomes.
Can you tell us a little bit about that?
Um, we've got quite a, a range ofresearchers across different types
(05:26):
of arthritis going on, so we'vegot people looking at the onset
of rheumatoid arthritis and tryingto predict it before it happens.
And there are blood tests thatwe're, we're trialing now that
might be able to predict who'sat risk of rheumatoid arthritis.
We've got people looking atpsoriatic arthritis and again.
Trying to maybe look at peoplewith bad psoriasis before they
(05:50):
develop the joint problems.
And what benefit could thathave if you know beforehand
that you're, you are at a risk,
you save people a lot of suffering and yousave the NHSA whole lot of work and cost.
So it's got huge benefits for individualsand huge benefits for the health system.
And prevention is something that,um, the government cares about and
(06:13):
has made open statements now thatthey wanna move more from treating
disease to preventing disease.
So that's one strand of work thata couple of my colleagues are
focusing on is, is trying to preventthose immune arthritises starting.
So does that mean thenthat there is medication?
So if you know that you're at arisk, there is actually something
you can do to prevent it.
(06:34):
There.
There are things that can be done
and that's, you can start to runone of our research groups now,
Caroline, because that what peopledo is first of all identify, can we.
Pick with reasonable certainty, somesort of high risk group, and then
you start to trial what you've got.
Based on what we know about the howthe disease works, you start to trial
(06:57):
various drugs in that group of people.
And this has been starting the last fewyears round 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 trialsin that area now to see if
they can stop onset of disease.
So as I say, that's onedisease area we're working in.
(07:20):
And then we work across anumber of other disease areas.
And my particular interest is inosteoarthritis and tendon problems
because as I said, they're very common.
We don't have any many drugsthat help at all at present.
Um, the common therapies we use for,um, uh, common joint pains are oral,
(07:44):
anti-inflammatory drugs, and mostpeople will pop an ibuprofen or.
Naproxen at some stage in their life.
'cause you don't just useit for arthritis pain.
It's used for headaches,it's used superior pain.
It's used for a whole range of things.
So, uh, but those drugs, theyhelp arthritis pain, but.
(08:05):
For mo, for many people, they can'ttolerate the pill and, and I think
patients sometimes feel guilty andit's just a, a side effect of the drug
and many people can't tolerate 'em.
So we think about 60% or more people can'ttolerate the drug or shouldn't be on it
because those anti-inflammatory drugs canraise your blood pressure, put you at risk
(08:27):
of heart attacks, can stomach bleeding.
There's all sorts of side effects, so.
We're pretty cautious about themand 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 verywell in the trial, in the trials, and
(08:51):
it's probably because opioids workcentrally what we call in our brain.
They don't work at the joint levelwhere, where anti-inflammatories
are working and where some of the.
Uh, new therapies might be working.
So that comes to a big question, which iswhere does pain come from in our joints?
Yeah.
(09:11):
And it would surprise manypeople to know that if we.
Grab people off the street andstarted doing x-rays and MRI scans,
we'd find a whole lot of problems inpeople's joints that have no symptoms.
So there's a whole lot of structuralproblems in your joint, in the joint
lining cartilage, the, the sort oflining layer that protects the joint.
(09:34):
There's a whole lot of problemswith cartilage and bone in
most, in many people's joints,especially over the age of 40, 45.
Um, but mostly they don't have pain.
So a big problem for my specialties hasbeen working out where the pain comes
from because that would make sensefor us to then focus in and treat.
And, and a lot of my work has beenlooking at that, where we think now
(09:59):
that a lot of the pain comes fromis not the sort of stuff you can
see on an x-ray, but soft tissues.
So around a joint is wheretwo bones come together.
At the end of the bone, you've gotthis smooth white cartilage stuff the
same as the end of a chicken breast.
That rubbery stuff that works as a shockabsorber wrapped around the inside of
(10:21):
every joint that nobody's ever heardof is a thin layer of cl wrap called
the synovium, and that lubricates yourjoints in rheumatoid arthritis, it's
the synovium that gets inflamed anddamages the joint in osteoarthritis.
The cartilage and bone are damagedprobably through minor injuries when
(10:43):
we're young, or major injuries whenwe've torn a ligament or something.
Um, but the pain is something different.
Um, so, and there are many peoplewith bad x-rays and no pain.
And the answer to that lies thatthe things we don't see on an
X-ray and often not on an MRI scanare the tendons and ligaments and
(11:04):
where they attach to the joint.
And we think that's where a lotof the pain comes from, is where
the ligaments and tendons areattaching onto the joint and, and
how helping keep your joint stable.
So if you are weak.
You take a lot more strain throughthose areas around where the tendons
(11:24):
and ligaments are attaching, and I'ma bit obsessed with getting people
strong because everybody I see in cliniccan't undo a jar, can't get out of a
chair easily, or can't get out of acar easily, and they're all pretty good
signs that you are weak if you've notbeen able to get out of a chair without
(11:45):
using your arms to push yourself up.
If you had to stop having bathsbecause you can't get out of the bath
anymore, that's a pretty good sign.
You've got weak leg muscles,um, can't undo a jar.
You've got weak hand muscles.
And the other signs of being weakis, is difficulty with, uh, doing
(12:07):
buttons and you become clumsy andsuddenly the kettle, a 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'regonna take four to 10 times more
strain through your tendons.
Suddenly you start to wake more,suddenly you start to hurt when you
(12:31):
walk up and down stairs because youdon't have good leg muscle strength,
you are hurting on the steps.
Um, I think this is a familiarstory to many people I talk to,
and the reason it happens is weget older is we tend often to get a
little less active as we get older.
And academics, like me spend alot of time sitting in the office
(12:53):
and putting on weight, not.
Staying a little bitactive and staying strong.
So one cause of joint pain.
One of the big causes of joint painis probably the structures that
surround the joint, the tendons, andwhere the tendons attached to bow.
And we and many other groups aroundthe UK have done a lot of work on
(13:14):
getting people stroll and showing thatit reduces pain very substantially,
as much as a pill would do.
That's extraordinary, that actuallyit's reversible at, at no cost really.
You don't need to joina gym to get strong.
You can do many things around thehouse and, um, just out and about.
Um, that
absolutely extraordinary.
(13:35):
And it takes, it takes some time.
And, and taking a pill takes 10 seconds.
Yeah.
Um, and often what I'm askingpeople to do takes 30 minutes.
A day.
And that's hard becausemost of us have busy lives.
You know, kids work, family,everything takes their time.
(13:57):
So, uh, I think one of the keythings for life is, is cutting off
some time to look after yourself.
And that's a really hard thingfor lots of people 'cause they've
got so many carer responsibilitiesand other things in their lives.
I suppose it's very easy to say,isn't it just 30 minutes a day?
You know, you've got, youknow, 24 hours you come on.
(14:20):
You can find that.
But actually when you put it likethat, it, it, everyone is, uh, is
fighting different battles, aren't we?
And the other thing is, first that I liketo do it in a sort of structured way.
My motto is, first, getstrong, then get fit.
People come to me who can't do astraight leg raise with their leg.
(14:40):
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 um, if you're weak,then you can't be fit.
You cannot be fit because youcan't work, walk and aerobic rate.
You can't do things.
So I think just telling weak peopleto go for a walk every day, it's
(15:03):
probably not a good thing to start with.
First, let's get you strong and,and a simple thing everybody can
do is walking laps in a swimmingpool, just in the shallow end.
Walking 30 or 40 widths of the foot ofa pool, that feeling of pushing against
resistance, um, is a good starterexercise to start getting you strong.
(15:25):
And there's, we need more pools in leads.
I think we need more access to pools.
It's not cheap for some people to getaccess, but at least now there's women's
only sessions and there's a few morevariety for things, for people stuff.
But I, I do know it's a.
(15:45):
To be able to, to access that.
So that's one way ofbuilding lead muscles.
Um, and for hand muscles, uh, just puttinga cushion on your lap when you watch tv.
So you're resting your forearms, puttinga squeeze ball or a sock, a man's
sock rolled in a ball in one hand, andsqueezing until your arm drops off.
(16:08):
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 squeezewhile resting your forearm.
And that will reverse mostpeople's grip strength problems
(16:28):
and reduce their hand pain a lot.
For osteoarthritis.
The best thing we can do in the communitynow is get everybody strong and then
I'd have 50% less patients in clinicturning up with, with joint pain.
If we could get most people strong.
You think it would havethat gut pick effect?
I think, yeah.
(16:48):
The, the trials suggest big effects.
If you have trouble in doing a jar, if youhave difficulty getting out of a chair.
You've got a problem that needsaddressing, 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 strongall your life and maybe such therapies
are never going to work well in peoplewho are older who can't do things.
(17:12):
So we are gonna need drug therapies.
One of our research projects we're runningat Leeds at present is indeed an an online
program we've developed, uh, at digitalintervention that you can use on the
computer or on your phone, um, called D.
We're just going into human trials now.
(17:33):
We're just doing trials with largenumbers of people now, for anybody with
hand pain, wrist pain, or elbow painbecause they're all connected, all use
the same muscles, and we're runningthis program now to see It's taken
a lot of development with patients.
We've worked together withpatients, which is the modern way.
We do research.
(17:53):
We.
Come up with a question, we takeit to a group of patients and
say, is this a good question?
Do you care about this?
Then we work with them to co-designwhat an intervention would look like.
And in this case, we had a lotof input in what people wanted.
Um, and so now we've gottatrial it and see if it works.
(18:13):
And the problem for modern medicine andthe problem for the days of an internet
that's so open is there's so much false.
Knowledge, false evidence out there thatreally is harmful to people who have
pain and suffering and fatigue and allthe things that go with pain, um, who
end up often spending money on a lot ofthings that are just a waste of time.
(18:37):
And that, to me is a real, that's thedownside of modern times, isn't it?
Internet is a huge force for good in, inspreading information and communication.
But the downside is all themisinformation and lies that are out
there, and at the end of those liesis often somebody making some bucks.
Um, so you've gotta watch for that.
(18:59):
So this research, obviously you cansee how it has the potential to impact
a huge number of people because you'retalking about doing relatively simple
things, um, at relatively low costs.
What's the importance of, of, of allof this research sort of globally,
(19:21):
not just for us here in Leeds.
So, um, leads in the arthritis fieldhas been, um, a big international
leader in a number of areas, um, inrheumatoid arthritis, in psoriatic
arthritis, and in osteoarthritis.
The the things we do, we often collaboratewith other centers around the UK in our
(19:43):
trials and interventions, and we've got a.
We all are part of internationalguidelines, and so I think
there's the coming up with newtherapies piece of work, that's,
that's one strand of what we do.
There's some of that involves drugtrials, which involves patients.
(20:06):
There's international guidelines for howwe, uh, treat things that that influence.
Thousands and thousands of doctors acrossEurope and and the world, and we've
been part of many of those guidelinesand those modern treatment guidelines
are all based on basically trials.
It, it's saying, you know, wasthe trials of Drug X effective?
(20:29):
No, it doesn't get in.
You know, it, it didn't work.
And, and that's what we want.
We want a real evidence synthesis.
So the research done heredoes percolate up nationally.
Does percolate internationally.
Um, and we've got goodevidence for a lot of that.
Now I've mentioned getting strong.
(20:51):
The other part of work wedo is, is looking at drugs.
So I've mentioned we don't have manydrugs for the pain of osteoarthritis.
And one of our other areas is, is tryingto, um, look at new drugs that are
coming along and seeing if they work.
And it's not a small business, it takes.
Uh, even a small trial, a sort offirst early trial of, um, a new
(21:16):
therapy might need 50 to a hundredpatients followed over three to six
months, sometimes out to two years.
Um, so it's a lot of work and the costof those trials when we're riding grant
monies for these trials can cost two to 3million pounds to do one of those studies.
So that's why we're not doinglots and lots of trials.
(21:40):
There's a limitation in,in and what we can do.
Um, but we've worked with industry,with companies that are developing
new products and want put them throughthe rigor of, of a proper trial and.
Um, the recent ones we'velooked at, we're still waiting.
(22:00):
We finished a trial a while ago ofa, an injectable chili pepper, if you
like, something that most people willbe aware if they keep eating chilies,
they can take more and more, so theirnerves adjust to the, the chili pepper.
And people have been tryingto do injectable forms.
That reduce people's pain andwe waiting on results of trials.
(22:21):
Trials finished.
We're waiting on results to see ifthose trials are gonna be effective,
may work short term, which won't.
What's the link between the pepperand the, the stopping of the pain?
Okay, so pain arises from nervesand it arises from the nerves.
I've, I've said the tissues that areinvolved, the sort of, um, tendons
(22:44):
and where they attach to the joint.
But at those points you've got lots ofnerves, what we call nociceptive nerves,
the nerves that conduct pain signals.
And what the chili pepper does isaffects a molecule called tr trp V one.
So these molecules, um,make the, the nerve shrink a
(23:05):
little bit temporarily shrink.
And that's what's happening when you'reuse eating lots of chilies is you're,
you are desensitizing your tongue nerves.
And that's what we're the same thingwe're trying to do inside the joint.
Now as well at the, at the end ofthe nerve, there's not just the T RRP
(23:28):
V that I just mentioned, receptors.
There's other little re uh, moleculesthat are conducting pain signals.
And probably the most exciting thingwe've been involved with recently is, uh,
a new drug that modulates another nerve.
Um, pain conductor calledin Neurotrophin three.
(23:50):
We've shown that that a drug that mopsup Neurotrophin three dramatically
reduces people's knee pain.
And we've presented that trial,we've got the results of that
trial and was very positive.
Um, and we presented that at the AmericanCollege of Rheumatology meeting last year.
(24:10):
And now the company that's involved withthat, which is a small UK startup company.
Um, is looking to raise fundsto do a much bigger trial.
I, I think one more big trial couldbe, could see that get through to
humans in the next four years or so.
So that's on the cards, but it's aboutraising money to do the trials and
(24:33):
that's the sort of business side ofthings that we are not involved with.
That's that's outside of us, butwe try our best to, to be ready to
do the trial when it comes along.
That must be quite,
that's gonna be important.
That must be quite frustrating for,I, I imagine for you because you,
you, you do a smaller trial, you seeits success and you think, gosh, this
(24:55):
could be amazing for my patients.
But then there's, there's just notenough money for these other businesses
to then go and find the funding inorder to do these bigger trials.
And for that to then, you know,become a, a, a normalized procedure.
An osteoarthritis, although it'sincredibly common, has not been
so sexy for big pharma to look at.
Yeah, and that's because there's beena whole lot of drugs tried and failed
(25:18):
and therefore people really want tobe risk averse in that area, but, but
there is always an interplay in our.
World of business versus, um, youknow, health, healthcare and, um, yeah.
So sometimes you wishthings could move quicker.
We also did a positive trial a fewyears ago of a common drug use for
(25:40):
rheumatoid arthritis called methotrexate.
And we did a trial in osteoarthritisthat showed that indeed it did reduce
the pain of osteoarthritis and.
We're still working out how tomake that, uh, because it's a drug
that it has some side effects.
About 70% of people canstay on it, but 30% can't.
(26:02):
It needs monitoring withblood tests over time.
And before I can say to all the gps,you should be using this drug, we
think we've probably gotta find the.
Patients who will get most benefit.
So we sort of restrict the numbersof patients, um, and make it
more feasible for primary careto be able to use that drug.
(26:24):
So there's another drug where we'vegot preliminary evidence from a large
trial that it works, but it's how tomake it fit into clinical practice.
So I think now you'restarting to see the spectrum.
Research is involved with, there'snon-drug therapies, there's drug
therapies, there's getting things throughtrials, and then there's getting them
(26:47):
into the routine practice if I've got agreat drug, but it's really, you know,
hard to monitor and it takes a lot of workthat's no good for a primary care system
that's already overwhelmed and barelycoping with what they've got to see now.
So all those things comeinto what we weigh up.
(27:09):
There's, there are somany components to this.
Before you, you actually end up as apatient with a drug or a body of physio
work that you can do and take on.
There's so many differentcomponents and so many years,
it's its own game andyou've gotta understand it.
And luckily now we've got a lot ofpatients who've been involved who
do understand and they help path,uh, you know, grease the tracks for
(27:33):
other patients to come in and, andunderstand the processes and things.
But yeah, it takes a longtime to get things done.
You have to be patient somewhatto be a researcher or big, crazy.
Both of those things help.
And if you'd like to find out moreabout anything you've heard about in
today's episode, just check out the shownotes coming up on our next episode.
(27:54):
The AI algorithm is called FIND af.
It was developed by ourselvesat the University of Leeds.
We developed and checked 2million people in the uk.
We've now done that in 9 millionpeople in other countries, so this
algorithm could go much further.
Internationally, globally, and it canactually be something that we export,
can an algorithm predict a strokecould lead to be changing the
(28:17):
face of worldwide healthcare.
That's all coming up in our next episode.
Medical Breakthroughs.
The research journey is anunder the mask audio production.
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