Why does my knee hurt?

hello and welcome to this edition of joint action [Music] this podcast is dedicated to all those out there who have osteoarthritis aka crumbly joints on the show we unpack the truth and demystify the myths about the disease and its management if you have joint pain and want to know more about how to manage it from the world's best experts you've come to the right place without further ado it is time to welcome your host david hunter hello and welcome to this edition of join action this week we have the privilege of discussing why does it

hurt and we're joined by none other than jason mcdougall and jason's lab employs an integrative approach to examine the role of nerves in controlling joint inflammation and pain his lab uses a lot of different techniques to record the function of nerves to investigate their activity in joint related conditions his aim is to identify novel drug targets to help relieve joint disease inflammation and pain and he's got a lot of different research interests including arthritis pain inflammation receptors related to that and specific agents including cannabinoids which we will hopefully get to as part of this discussion

that he's quite interested in so jason thank you so much for coming along thank you david it's a pleasure to talk to you about this yeah it's a it's a challenging time and i'm sure you're experiencing this in in canada what uh what sort of impact is the virus having on your day-to-day life and your lab and your family well it's having a huge impact of course like like with everybody basically the the lab is shut down and nobody's doing any experiments we're all in lockdown at home working on papers maybe trying to catch up

on some reading and coming up hopefully with the next next best ideas so it's it's been very difficult to be remote from from my lab members from the team also other people in the department it's having a huge impact how are you staying in contact with with your group so regular emails try and keep it light have a little bit of a joke the old zoom meetings things like that that's yeah just just trying to keep in contact and keep the morale up as as best as we can yeah and i see uh i see

you resting in a very comfortable chair with a nice sheepskin down there in the basement is that is that getting a lot of use at the moment it certainly is this is my new office very very comfortable the sheepskins keeping me warm and keeping me company during these cold days so yes this is this is where i do my uh do my work from now oh well stay stay well stay safe and i i wish you all the best for this really challenging time we might get in and start talking a little bit about the

topic at hand why does it hurt but in the first instance i just want to learn a little bit more about you and so if you could describe yourself in five words what would they be well that's a difficult one i'm a very private person as well you know david i you know i have a good sense of humor maybe quite try and keep quite upbeat i have compassion for what i do and the people i work with let's see five words i'm enumerate so that's that's probably five cases right there for you oh brilliant

brilliant thanks jason and can you just expand a little bit more and just tell me a little bit more about what your research is on and what your what your group is focused on so we're really just trying to work out the complexity of osteoarthritis and joint pain as you mentioned in your kind introduction you know we have many different approaches to try and understand what's causing the pain uh within the joint so we do anything from very simple neurobiology of trying to understand how those nerves work how they sense the pain how they transmit

the pain to the brain how we interpret those signals and then trying to understand what different targets we could go after and develop new drugs to try and stop those signals getting from the joint into the brain so hence you know managing the pain it sounds sounds fascinating and i think i guess in the first instance just trying to put an overarching framework behind our understanding of pain there are a lot of different frameworks that are out there but is there a particular framework that you subscribe to that might help our listeners understand where pain

comes from well pain is extremely complex it's not something we like to talk about and there are many different psychological and social issues that contribute to what we all feel as pain there are many different types of pain so pain is not pain is no pain there's uh there's what's called no susceptible pain which would be for example you know you're touching something hot or you're standing on something sharp that very immediate alarm system in your in your body and that that type of pain certainly is a component of joint pain when maybe bones are

rubbing against each other it's that alert system that something is not quite right in our joints another type of pain is is inflammatory pain so where there's inflammation within the joint various different chemicals are being released into the joints which can then sensitize those those nerve endings in the joint and give us that heightened feeling of pain and then more complicated is as something called neuropathic pain where there's actual damage to the nerves themselves and we're finding that in patients with osteoarthritis and in some of our models disease models those nerves don't look normal and

the fact that they're not normal means that they're responding differently and they're also contributing to pain so it's a it's a very complicated interplay between these these different processes that we're interested in fantastic and if if a person is and it's obviously variable between people and within a person themselves but if we were to try to distill down what the main drivers of that pain are of the factors that you just spoke about whether it be inflammation nerve damage mechanical loading the psychological and social factors that you talk about again i'm probably making it hard

for you but if you had to try and identify of those which is the most important can you put your finger on it no because i think they all play a major major part and and you're right different people will have different components to their pain some people may have more of this neuropathic type of pain other patients might have more of an inflammation but certainly i i couldn't put my finger on one being more important than the other they all contribute to this crazy syndrome that we call joint pain yeah yeah and if you

could just expand a little bit on when a person is walking around and they're feeling pain in their knee their hip or their hand where do the signals for that pain start and how do we process them so part of it probably comes from the loading of the joint so when we're walking around um those nerves are become hyper are hypersensitized so even normal types of movement is now amplified and the brain now interprets those increased signals those electrical signals coming from the joint that we would normally just think of as normal movement as as

really quite painful also the the joint tries to repair itself so if it's being damaged it's been injured if it's got some underlying disease it's going to try and repair itself which is great but unfortunately the mechanisms that are involved in that and some of the chemical mediators that are involved in trying to repair those joints can have a detrimental effect they can they can sensitize those nerves leading to uh to heightened feelings feelings of pain as well so there's a mechanical component as a chemical component even just the the gradual breakdown of the joint

tissues like the cartilage in the bone etc release various chemicals which then themselves can also sensitize those nerves uh leading to to the pain phenomenon yeah and we'll touch upon those chemicals in a moment in terms of uh treatment targets specifically but before we get on to that just a couple of words if you could just explain a little bit further about the psychological social or contextual aspects that might influence a person's pain experience well we all deal with pain very differently some people may be able to cope with joint pain better better than others

so there's that uh psychological component comes comes into it it has a devastating effect on on people's quality of life and not being able to work not being able to you know hold a child or you know it really impacts our physical activity and that really impacts on an individual's well-being and over time if there's a detriment to the to the well-being that they may feel more pain and not being able to cope with it as as well so it's not just the neurobiology that that you know that we try and uh look at but

also that you you write that that whole psychological social component to pain is is also very important and very very complicated yeah and i think just to re-emphasize all of what jason's saying there i think the critical message there for people who are out there who have pain is if you're if you're depressed if you're stressed if you're anxious if you're socially isolated if you're in the process of losing your job potentially as a consequence of your your joint disease it's going to have an impact on your pain experience and so our ability to treat

and modify your pain using some of the treatments that we have at hand are great but they're limited if we don't address some of those other important elements that might accentuate your your pain experience if you could just i guess briefly touch upon some of those treatments and and how they might work on pain particularly those that people might commonly be used to using such as anti-inflammatories and opiates and other agents so certainly um there's there's no great way of uh controlling pain and what might work for one individual may not work for an other

individual so from a from a drug point of view of course the first go-to drugs are the non-steroidal anti-inflammatory drugs so some of these anti-inflammatories which which can be great uh they have obviously known side effects associated with them on our cardiovascular system on our heart also maybe on our on our kidneys and our stomachs etc so we really need to find better targets or better ways of trying to control the pain then we get on to uh use of opioids uh opioids again very effective for controlling pain uh they they're very beneficial but of

course there are a lot of known side effects associated with uh with taking opioids and i know a lot of people are probably afraid of taking opioids for fear of things like addiction or tolerance but i think in a controlled manner you know opioids would still play a very relevant role in helping managing pain for certain subsets of patients for anti-inflammatories if we just want to pick that one up first how do they modify pain are they are they actually targeting inflammation within the joint or do they work predominantly centrally how is it that they

work um well really both actually um they they can dampen down the inflammation that's occurring within your joint and maybe reduce some of those uh those chemical entities that i was talking about that can sensitize the joint the joint nerves but there are also um receptors on the nerves so things that these non-steroidal anti-inflammatory drugs can can bind to and can dampen down the signals being transmitted from the joint to the brain directly within the joint but you're right they can also act on the in the central nervous system for example at the spinal cord

where we know a lot of the pain signals can be amplified a lot of these anti-inflammatory drugs can also work at that level to try and tune down and like turning the volume down on on on your music system you know to prevent that transmission of the pain signals getting into the brain so they really work at multiple different levels yeah fantastic and we'll we'll have an episode coming up in a few weeks about the different pharmacologic agents that are helpful in the use of treating pain for osteoarthritis so you know for many years i

think a lot of people have spoken about the fact that many of the agents we do use are modest in their efficacy in terms of relieving pain and they have a range of known side effects related to them so as a consequence of that pain i think for many is is still an unmet need and so i guess just asking you the pointed loaded question do we need more analgesic agents for osteoarthritis i think so yes i believe that we need more targeted agents that can control the pain in a very as they say efficacious

very important way but also in a very safe way and and maybe not just be one drug at the end of the day but maybe a combination of different drugs that's that's going to help try to relieve that pain and at the same time trying to mitigate or minimize some of those nasty side effects that we sometimes associated with current drug therapies yeah and hopefully obviously in time targeted towards the typical types of pain that you spoke about before depending upon how a person presents whether that's more inflammatory or otherwise of the agents that you're

aware of they're under development which to you look most promising so for new agents there are a few areas that are looking that are up and coming that are looking very promising there's something called nerve growth factor so this is a chemical that's produced in our bodies that helps our nerves to grow and communicate with each other but what's what happens is in certain disease states like in osteoarthritis these nerve growth factors start to go out of control and instead of just having the beneficial effects of helping communication or nerve growth they're actually again doing

this sensitization of the pain sensing nerves within the joint and there's been development of various drugs antibodies that can reduce the the activity of the this nerve growth factor and that's been shown to be very very effective and at controlling pain there are still some issues associated with with this particular nerve growth factor antibodies but that's looking very promising another area as well and there's a lot of anecdotal evidence of of course and something that we haven't interested in is is cannabis and people have been using cannabis for thousands of years for many different indications

but there's this stigma associated with the use of cannabis and very much a social stigma associated with it that we maybe have to talk about and try and overcome but i know a lot a lot of patients that i talk to seem to gain a lot of benefit from taking certain types of cannabis not only just in being able to manage their pain but also helping with anxiety and the stress of living with these chronic diseases so that's another area that's that we're very interested in yeah it's an area of active interest for lots of

different researchers in the australia space and obviously as you say anecdotally a lot of a lot of patients out there have a strong interest in in cannabinoids as well if you could just briefly distinguish between thc and cbd and just explain those terms and i guess also just touch upon what part of cannabinoid process is likely to be most active and efficacious and i guess make comments about the merits or benefits of smoking marijuana versus using a cbd targeted agent so cannabis is a very complicated plant there are hundreds and hundreds of different chemical entities

that that are in cannabis and we're only just scratching the surface of understanding what those different cannabinoids are and what they can do so the two main ones that are investigated are thc which is tetrahydrocannabinol um and that's the the psychoactive part of cannabis that's the part of cannabis that gives gives the feeling of euphoria and highs but has also been shown to be very effective at controlling controlling pain as well and then the other main component is cannabidiol or cbd and cbd is is non-psychoactive it can make you feel a little sleepy but it's

uh but it doesn't have that euphoric effect associated with it and the cannabinoids not only can control pain but they can also reduce inflammation they've been shown to be anti-inflammatory so there is a lot of good scientific evidence as well on the cannabinoids showing that they have anti-inflammatory properties and also there's a little bit of evidence to show that it could maybe even help repair damaged joints and and repair those those damaged nerves that are associated with arthritis so they can work it again at many different many different components of the disease to reduce the

pain brilliant brilliant and we were lucky enough to have you down here relatively recently visiting and you gave an amazing talk about cannabinoids and some of the history related to that how long have these been used for uh for various purposes well again they've been used for you know thousands of years they were part of the the pharmacopoeia in in the early part of the 20th century there were i mean doctors were prescribing these these drugs there were many different medications that had cannabis in them and then the stigma started to overtake uh the science

there was a lot of research and development previously but then the stigma started to overtake it and a lot of those programs unfortunately were shut down thankfully we're starting to come through the other end with some really good science to show that you know there is something behind the cannabinoids and the cannabis plant that could be beneficial but again it's it's not for every patient not every patient is going to gain benefit from use of of cannabis but it's trying to identify those those patients and and using them in a in a responsible and safe

way yeah brilliant brilliant now jason what wasn't i smart enough to ask you about that i showed up during our chat today well if we could just maybe expand a little bit further on the on the cannabinoid system so they're also what are called endocannabinoids so we we talk about cannabis and smoking cannabis and of course smoking is not the most ideal way of administering any drug and using like you said targeted creams that maybe have cannabidiol in them maybe in the future the way to go but our bodies also produce their own types of

cannabis so these endocannabinoids we're probably familiar with endorphins so you know we go running or we eat chocolate we do things that we enjoy we get a release of endorphins in our body well they're also similar sort of cannabis-like compounds that can also have those beneficial effects now the problem with the endocannabinoids is is that uh that they do they don't hang around the body very long uh they're broken down very very rapidly and so they can't have their beneficial effects and one of the strategies that we and others have been looking at is thinking

of the enzymes that break down those those endogenous those naturally occurring cannabinoids in the body and allowing our body body's natural endocannabinoid system to take over and and then more of a natural sort of way or endogenous sort of way of controlling the disease and symptoms yeah that sounds brilliant really promising so hopefully hopefully we'll see more of that um are there any patient friendly resources that you might like to point us in the direction of that we could share with our listeners yes and i know in canada here um where the arthritis society they

actually took the bold move of wanting to put some funding into into cannabis research when it was had that great stigmatization associated with it and and they wanted to inform their patients in a responsible way about uh the the effects of cannabis and cannabinoids so uh the arthritis society in canada has some really good resources that are very patient-friendly so purpose i might grab that link from you and put it on the show notes after the call what's your biggest challenge in your role right now and how are you going to overcome it and obviously

we have the virus challenge at the moment that's making lives difficult for everybody but um i guess specifically from a research and pain perspective what's your biggest challenge and how you're going to get over it it's the same old thing unfortunately it's it's needing funding to be able to run the research it's extremely important that we have very good signs very robust science being done uh that people can trust the the science that's coming out and in order to to do good science and we really need to have research dollars to be able to to

come to some great conclusions to help everybody yeah and i'm i'm really hoping that in the current climate uh where we've seen the importance of health care and research that i think people's appetite toward research funding will will improve but if you could do anything again covered virus aside if you could do anything to improve health and healthcare what would it be well i think once again we need good solid scientific information coming out access to to drugs for patients affordable access to drugs for all patients i think is as is paramount those are the

those are the things that i see are going to be important to try and help beat this these diseases yeah i think um as you touch upon equity there's a big big problem everywhere and i think particularly when we're talking about access to cannabinoids for for conditions from which they've been proven to be effective their cost right now for many countries is extraordinarily prohibitive but if you could remove all barriers and constraints uh to your pet favorite project what would you do that's a difficult one um we we have you know it's not just the

cannabinoids that we're interested in we're interested in other different chemical mediators that are responsible for pain access to patient data access to patients information i gain more information sitting down and talking to an arthritis patient that i do with some of my scientific colleagues uh so dissemination of of information at all levels and an active participation of arthritis patients in research i think is paramount brilliant and i guess just in closing just a couple of quick questions but if you could have a billboard with anything on it what would it be and why yeah that's

a good one if there was a billboard that i would like to see it would be you are now leaving osteoarthritis painville population zero superb yeah a cure hopefully is on the not too distant horizon for for many of us but if if you can leave our listeners with a bit of advice knowledge of wisdom what what might you like to say in closing be active be positive we've talked a lot a bit about drugs today but you know one of the important things is to maintain a good exercise regime good you know the classic

be healthy good diet not to ignore your pain medications because as we've mentioned they're not just there to help control the pain but they can also have other beneficial effects like reducing inflammation maybe helping repair the joint and improving the overall well-being of people living with these chronic diseases yeah really sagely and important advice so jason thank you so much for your time your your thought your wisdom chat today it's greatly appreciated thank you very much david it's been a pleasure yeah and stay stay safe and stay well in these challenging times so for our

listeners that's all for this episode of join action between now and next time please do take care of yourself stay strong stay active please send us questions if you have any feedback for the show don't hesitate to let us know and thank you so much for continuing to listen [Music] thanks for listening to joint action with david hunter if you like our show and want to know more check out www.jointaction.info don't forget to subscribe to the podcast and share it with your friends and family and please leave us a review on itunes or your favorite

podcast platform if you have any questions you can email us at hello at jointaction.info and follow us on twitter at jointactionorg this podcast was hosted by david hunter edited by vicky dwong music produced by jordan hunter [Music] you