#73. Life With And Without Pain - Arnas Tamasauskas

Dive into the fascinating world of pain research with Arnas Tamasauskas, a PhD student at the University of Liverpool. Explore the mysteries of neuropathic pain, genetic quirks which lead to some people feeling no pain, and the use of MRI and interviews in understanding chronic pain and invisible disabilities. Join us for an enlightening conversation on the Smooth Brain Society podcast.

Chapters

• 0:00 Introduction
• 0:54 Understanding Neuropathic Pain and Its Origins
• 13:21 Investigating Stroke and Pain Connections
• 22:31 Therapies for Chronic Pain Management
• 29:19 People who can't feel pain
• 33:48 Complexity of Chronic Pain Diagnosis
• 43:28 Research Improvements and Current Gaps
• 54:43 The Participant Experience in Chronic Pain
• 1:00:37 Next steps and wrap up

Transcript

0:03

great. Hello, hello, hello. Welcome to the Smooth Brain Society podcast. Today, we're hanging out with Arnas Tamasauskas. He's a full-time PhD student at the University of Liverpool. His research digs into some wild and important territory. So why do some folks develop neuropathic pain after a stroke, and while others, due to rare genetic quirks, can't feel pain at all. He's using some brain scans called MRI to try and figure out what's going wrong. And in between the experiments, he's been interviewing people with functional neurological disorders and even writing a book about it. So basically he's juggling chronic pain, functional neurological disorder storytelling and brain imaging and all in one PhD sandwich. So this is intimidatingly impressive and we have him on today, which is great. So welcome Arnas, hello. So to start us all off, Arnes, can you tell us maybe a little bit about yourself and what's your PhD about? Even just a quick answer, somebody asked you at a party, what's your PhD about? Hi, thank you for having me. uh I know this is a podcast, but I still felt like I had to put on a funky shirt to look better for the uh imaginary camera. My research and my PhD is, it started off as neuropathic pain after stroke and through a lot of side projects to my supervisor's headache, um it morphed into just a research into pain in general. So a lot of things still stayed around neuropathic pain after stroke. And we're doing a lot of MRI scans with people who have had a stroke, but we are also working with people who have genetic conditions that resulted in them to either not feeling pain or not reacting to pain. And similarly reaching out to other communities of pain, such as people with diabetic neuropathy or with pharomyoelogy, just different aspects of pain that a lot of people don't know exist. I'm going to jump in and ask really smooth brain questions to begin with. So you said a lot of terms there, which I don't understand. what is it? What do you mean by neuropathic stroke, neuropathic pain? What you said and sort of like the basic sort of thing, someone who does not know, who's not in your field kind of needs to know to understand your work. uh Yeah, I think I'd like to start off by kind of creating a distinction between three types of pain. you usually have acute pain, which is pain that most people will be, ah most people will know and have experienced such as, ah you know, getting a paper cut. Then you have persistent pain, ah things like if you break your arm or for example, get a piercing, pain that continues to linger after while you're healing. And there is also chronic pain. it's essentially pathological pain that doesn't really serve a purpose in protecting your body, just kind of a nuisance to you. And the reason why people get chronic pain, there is quite a lot of different origins for that type of pain. So with stroke, if you get a lesion in your brain, in an area that is responsible for stroke, such as the thalamus. then it's likely that that area becomes very overactive and it's like ringing alarm bells all the time saying we're in pain, we're in pain, ah but then the body isn't actually in injury or in pain. So it just creates this kind of, I don't want to say psychological, but essentially meaning that there is not any damage to any specific part of the body, but you just feel pain there. That's very interesting. you're sort of uh based on Beth's intro, you're sort of looking at people with sort of the sort of chronic pain versus people who do not feel pain at all. um Where does that come in sort of like, I know Beth in the intro mentioned it's genetic, but could you describe what it's like? Yeah, of course. uh So we call it congenital insensitivity to pain. uh And it's essentially specific genetic uh changes usually to a type of protein or a neurotransmitter. So we have a group in Sweden of people who are related to each other. You know, being genetic, it's very likely to be passed down in the family. So these people have an R221w gene. And it essentially makes your nerve growth factor or active. It's a protein that, um, essentially helps in forming, uh, nerves. so, uh, their peripheral nerves are impacted, meaning that, you know, you prefer like your arm, if you, if it gets injured, the pain isn't, uh, relayed into the brain properly. And so the. get these signals into the brain, they're a lot more subdued than a normal pain would result in. And they just don't have, don't really feel a compulsion to react to pain. So if they have their hand on a stove and it's really hot, they might leave their hand on the stove for a lot longer than a regular person would. Even though what we found is that they still feel the pain to the same degree, they just don't feel like they need to reduce the pain. uh So this is quite an interesting case in a way that They feel pain, but they don't react. But we've also had this lady with overactive cannabinoid receptors. um So as you might know, um we produce cannabinoids in our body, like THC, CBD, but not enough to actually get high. Well, this lady, she produces enough to actually get slightly high. So she's happy in life most of the time. uh And she's actually not feeling a lot of pain, which has resulted in her getting some... fairly severe injuries, but remarkably little scarring on her body, which would indicate that her regeneration is a bit higher than an average person. So if the driver was a real life superhero, would be Mrs. marijuana, Mrs. Super ganger. mean, that's the dream, right? Being just high enough that you're just enjoying life the whole time. Yeah, and guess superheroes are always kind of somewhat based on real people. Maybe this lady is the inspiration for superheroes we're seeing nowadays. eh So basically what you're kind of looking at is like almost two ends of the spectrum. So you're looking for people who actually feel or feel or feel the pain, but don't necessarily do anything or don't feel any pain in those who have like really kind of like chronic pain, which you just shared what that meant previously. em Can we learn something from each of these disorders which can help the other one? m Yeah, so I'm sure that the chronic pain definitely helped. I'll let you answer that one and then I'll carry on with my next question. Yeah, it essentially helps us build a pain connectome. So understanding different pathways that result in pain because pain isn't in your body. um If you get injured, if you get a cut, the pain isn't coming from the cuts. All of the pain sensations are located in your brain. And there's remarkably a lot that we know about pain and remarkably a lot that we do not know about pain. So we know some circuits that talk to each other that result in pain. So Like I mentioned, the thalamus being a big center that gets information that goes from your cut to your spine to the thalamus and then it decides where to relate further. But there's also areas like the insula cortex and anterior cingulate cortex who work together to determine which sensations deserve attention. So you can only focus on specific types of pain and Understanding more about how those secondary systems work allows us to understand better how pain works in general. And so in the example of the pain intensitivity, we found that a lot of those changes are in the anterior cingulate cortex. So as we kind of would expect, we have a lot of research showing that chronic pain like pharomyalgia results in an overactive ACC, whereas with pain intensitivity, what we found is that you know, you would expect there to be an under activity of ACC, you know, if you have too much, you're in pain. If you don't have enough, you're not in pain. But what we found is that some parts of ACC are better connected in people with pain sensitivity, but they're not as efficient. So there is still a lot of activity there uh and there's more connections, but they're less adapted to pain. it's kind of improved, creates a more complex idea of how pain works and how the pain kinakotone is formed in the brain. Yeah, probably sense of basically how it kind of speaks to the parts of it. I'm gonna say something wild for us three, but know, thinking when you're saying it, what if we just took the anterior cingulate cortex out? What if we just got rid of it, what would happen? Would that mean all pain would be gone at that point? Or would the person no longer be functioning? I think that's a very interesting uh thing to speculate. ah can't think of any famous cases that have resulted in that, but there is a pretty famous case of uh an amygdala stopping, where an amygdala stopped working. So amygdala is quite an overactive area in fibromyalgia, and it also is used in navigating emotions and regulating emotions. There was a very famous case called SM. of focal bilateral amygdala calcification. It was due to lipoid pyrtonoises, uh which is to simplify the amygdala essentially calcified and became solid as rock. So this lady uh wasn't feeling a lot of pain and wasn't feeling any fear. So she had a very interesting life to her detriment and also to her advantage. uh There's a recorded interaction where she was walking through a park in the middle of the night and someone tried to actually mug her and demanded money with a knife. And she just looked at him and said, God be with you and walked off. uh Only to come back through the same park the very next day, like nothing ever happened. So, you know, it of shows how, you know, things like anterior cingulate cortex or insula or the amygdala to have multiple functions in pain. And also there is knock on effects. another areas such as fear. um you know, it's quite interesting seeing weird cases like this where you can see what happens when you knock one part of the brain off. Yeah, speaking of that, I gave a talk recently where I spoke a bit about the amygdala. On the opposite side of that, there was a gentleman who had, I believe, had a tumour pushing on his amygdala and he actually, name's Charles Whitman, and he actually had kind of like a very aggressive response to it and he was very scared, very aggressive, and he ended up uh shooting, I think, 30 people in the 60s. So sometimes when these things don't work or there's more function or less function they can work with and wonderful ways that we just don't know about. So we'll say that we probably shouldn't take out the anterior cingulate cortex. Probably, I think it has something to do with em behaviors and kind of linking uh different kind of processes and stuff, I believe as well. So, okay, we'll keep that in, not one for the moment. that's all right. I will say that, taking out the ACC was kind of how we realized that it does relate to pain. Um, back in the day when lobotomy was still the thing, the, you know, the hot thing to get when you're, uh, don't know what to do with your life. they, they use the lobotomy to take out parts of the brain, including the anterior single cortex. ah And he found that low-autumn patients still felt pain, but didn't really care about it. So it essentially showed that, um you know, it's an important part of ah brain's response to pain. And that's why we know that it does. And it was further confirmed by MRI scans in the more modern day age where we don't have to remove parts of the brain to know what to do. You give you giving ideas to the military, all the soldiers, you get get rid of their ACC and then they won't give any information if they're caught as prisoners of war or whatever. Yeah, why have you said that? That's it. In 50 years time, we're going to go back to this podcast and be like, see here, who's saying it was the one who said it, and that's where we first got the idea. I'm sure they came up with it. I'm pretty sure it's like that thing, right? It's that rule of the internet. you think the podcast is getting closed down, just get a text. Okay. So you said you do this via MRI. um are you then, I guess you said that you do it in people with stroke. So are there particular strokes you look at, or is it any stroke after which you're looking at? these pain responses. Um, yes and no. Uh, I would say that we don't particularly discriminate whether it's ischemic, meaning if it's a blood clot or if it's a hemorrhage, meaning a bleed on the brain. So we look at both cases, uh, just because you know, pain happens in both cases, we do discriminate in a way that, uh, because of the nature of the MRI, people do need to be able to, uh, walk a few meters to get to the, um, MRI scanner. and to also be need to be able to respond to some questions and sensory testing that we do. So we tend to recruit people whose stroke isn't severe enough that it will hinder the scan. But when it comes to the type of scan, we tend to accept everyone. And with the neuropathic pain after stroke, it used to be known as thalamic pain, just because it used to be taught that only strokes in the thalamus would cause neuropathic pain. uh But it's time we realized that pain can happen if you have a stroke outside of the thalamus. And if you have a stroke in the thalamus, doesn't mean that you will have pain. So it kind of complicated things because now we don't really know what causes the pain. We have some ideas, but we're still exploring them. Could you give examples of some of these ideas or is it not really worth discussing? Yeah, so it kind of goes back to the Talon. So it relays a lot of the pain information into the sensory cortex. And I'm not sure if you or listeners have heard of the sensory homunculus. I really recommend Googling it because it's kind of stuff of nightmares. It's essentially this uh cartoonish man with a giant head, uh giant feet and arms. It essentially uh, depicts the nerves and processing centers of the brain and how much is allocated for each. So our fingertips are the most sensitive to sensations and to movement. is our face and it, the telomere, sorry, the sensory cortex kind of overlays this homunculus where at the very bottom of the sensory cortex in the sulci, uh, you have your face. then as you go up to the top, have your arms and legs. And similarly, those kind of layout also results in areas that are more responsive to vibration and pain. And kind of goes back to Bronwyn areas back in the olden days. The brain used to be kind of segregated into areas that were numbered and lettered and That kind of was partially debunked, but we still use some of lettering. uh I know it sounds a lot very complicated and I just threw a bunch of terms out to you, but it just means that the sensor cortex has different areas that represent different parts of the body and also tear-lettered for us to know what we are. So in the very sulcus is an area responsible for pain and vibration. And that is also where some of the finest uh sensations uh lie, like the face. So we think that a lot of pain comes from that specific area that's responsible for your most sensitive areas and that has been implicated in pain and vibration in the past. I can quickly share a photo of it if we wanted, if listeners did want to have a little look on the podcast. Because I think it's something that can only... Because I think it's really the best way to... Yeah, if you're watching it on YouTube, you can definitely see it. You're watching this podcast on YouTube. then they'll make you want to watch it on YouTube. So this is, this is the Somato Sensory Homunculus. Yeah, that's correct. A very deformed human person that will definitely be the stuff of nightmares for some people listening to this podcast. Glad we could share that. No, but that's very interesting. So we're assuming that if strokes are in certain areas where, I guess, there's less sensation, you should in theory feel less or less likely to feel neuropathic pain then as opposed to like more sensitive areas. partially. Yes. So, it, the sensations that you get relate into from the thalamus into specific, uh, body parts. So that kind of makes the pain localized in those areas. but like I mentioned, the sensory cortex is also segregated into different broadband areas. So it's kind of like a double whammy. It's travels to an area that is known for pain. And then it also travels to an area of a specific, body parts. So, broadman area means that there's pain and then the Homunculus shows kind of like where the pain is. So, the sensor cortex has a lot of uh different differentiation. It's a very tickly packed cortex and it's just responsible for so much. when things go wrong, it's very, hard to figure out how to fix it. And because we speculate on that area, we can then kind of speculate on how to treat it uh in our... Hospital in the Walton Center, we use a transcranial magnetic stimulator and essentially sends very strong magnetic pulses into a specific area and disrupts the function. So let's say if the hand area is very overactive, we can theoretically send pulses into that area to then induce under activity and to normalize people enter pain for a couple of weeks. And this is about 50 % effective in patients. But when it works, it really works really well, especially for people who are in health by medication. But we want to improve that to hopefully 100%. So that's why we want to look at areas that could be implicated and that we could target better like that area I mentioned. And so from what I can tell as you're saying is, usually it's usually the thalamus, that's the place that they most think is affected with this pain. Is it specific area, like very specific areas on the thalamus that link up to those areas in the somatosensory or the homunculus cortex that's causing this? it's, em so although the thalamus is quite large area in the brain, which we call like the kind of the central area, processing area where everything has to go through. is it literally could be like a couple of millimetres and that's affecting something like further up the brain. Is that what's happening basically? Yeah, yeah, exactly. So it's the ventral posterior lateral nucleus. uh So it means it's kind of at the top side of the thalamus. It's one of the main areas of sending information into the sensory cortex. And yeah, there's so many moving parts, so many tiny, tiny areas of the brain that are a lot more important than we realize. Yeah. And it can be, can it be, is it anywhere on the body or is there some areas of people tend to have more chronic pain or is it just all over or is it like, yeah, like focal? Yeah, that's a very good question. think it really depends on the pain condition. So with post-stroke pain, we tend to see it usually being um lateralized to one side. So if it happens, it's usually down the whole, usually the right side of the body. And it is often localized into the arm, but it is quite often just the whole side. And it is so severe that people cannot. you know, to struggle very close to struggle sleeping because any brushing sensation just irritates it and sends it into overdrive with conditions like fibromyalgia or diabetic neuropathy that again changes because the pain centers of the brain are a bit different that are responsible for it. So with diabetic neuropathy, usually it's all in the feet and we see that it's due to the nerves in the feet are getting damaged and then creating over activity in the brain and the pharomyoelogy it's a lot more varied. I think that's why pharomyoelogy is so difficult to diagnose and a lot of GPs are uncertain when diagnosing it just because you know it's such a non-specific type of pain that it can be anywhere in the body and it confuses a lot of clinicians. That sounds really difficult. You mentioned that there's a thing about trans magnetic cranial stimulation, TMS. is there any, so that sounds like it works 50 % of the time. Is there anything else, any other drugs or therapies in any way that work? Yeah, we found that amitryptaline and duloxetine, so they are both antidepressants, they tend to be the most... Cansepti can be the most effective, but essentially they have the most support for having effects. And we found this out during our review of management of post-stroke pain. While these antidepressants are usually the most effective... They don't work for everyone and that leads people to look at other solutions or they might not be super effective. For some people, it knocks the pain from 10 to a 1, for others it knocks it from 10 to a 7. And then they seek other things like TMS or in some more severe cases, deep brain stimulation. So where they implant a stimulator into the brain. That seems to be the most effective most of the time, but it does require brain surgery. So people tend to avoid that one. Yeah, very fair. I guess this type of em fibromyalgia and these pain conditions, it must get so awful. Is there quite a lot of, I don't want to go ahead and use the word charlatans, but are there quite a lot of people who maybe take a bit of advantage of people in these circumstances? Oh, 100%. uh I have a lot of beef with chiropractors. Not to upset all chiropractors listening to this, uh but people don't realize that it's an unregulated profession. And there is a lot of neurological cases where there is some real damage and people are left paralyzed after a chiropractor, which is why we... You know, don't offer it on the NHS. We offer physiotherapy and occupational therapy. You don't get the satisfying crack of a bone, with physiotherapy or occupational therapy, but it is, you know, scientifically proven and it doesn't have, well, usually doesn't have any negative side effects. And I think there is a lot of discussion around acupuncture. We, you know, it's very hard investigating acupuncture and I think it depends a lot. on where you're from. In Asia, there is a bigger belief and there is more placebo, but a lot of studies have shown that you can't attribute everything to placebo. there is some effectiveness to it. People try to map out the acupuncture areas of the body, but it shifts so much in practice. That is all just to say that we don't know how acupuncture works. It seems to work better in yeast. Asian populations just because um there is more of a belief in that. there's another placebo effect, but it seems to also be effective in Western populations where there's more skepticism. So it's one of those things where science is kind of unsure how it works, but it seems to work. Yeah. What about like alternative medications? I know these are therapies you talk about with chiropractors and stuff, but what about, know like use of cannabis is I guess the most simple of one, but then there's other people who like sell magic beans essentially. I guess they all have the same sort of placebo level effects, isn't it? If you believe it, then there's some. I do think that uh weed is very effective pain relief. I mean, we know scientifically that it is um THC and CBD work on different pathways of the brain that relate to pain. And one of the people that came to my study, he had a really, really major stroke. know, almost half his brain was missing. He was still able to do things with his wife, travel, but he said that His favorite thing is just to get stoned and watch YouTube videos. So, you know, when you're quite impaired, helps with regulating your emotions, it helps with regulating pain. And a lot of countries have, you know, done it successfully and even the UK can get a prescription for medical cannabis in some cases. It's just a lot harder to do so. And yeah, it's one of the things that needs more attention. Recently, there has been a lot of interest in ketamine. So scientists love ketamine. If you do different reviews, well, I mean, they love researching ketamine and, you know, they are outgoing enough, they also love ketamine. So there is a lot of studies that have come out over last five years where I think they're just looking for an excuse to buy ketamine. They just like to throw ketamine at every single condition that they can find. uh So yeah, there's a lot of stuff with ketamine and MDMA. It's quite popular at the moment. And guess previously you just said that woman who feels no pain, that was one within her cannabinoid receptors as well. I guess what you're doing here is actually coming up with a real world reason why actually we should be allowed to smoke weed. I mean, magic mushrooms, right? Psilocybin is also used a lot for, but that's more for mental health treatments as opposed to sort of neurological conditions and pain. But yeah, that's another thing which scientists love to money at or want to throw money at. I don't think the permissions are a little bit more restricted on that one. Absolutely, yeah. Yeah, there's some uh more interesting things like capsaicin that is essentially uh over exhausting your receptors. So capsaicin, it kind of synthesizes you. So if you inject capsaicin and then you touch a hot object, it kind of feels more painful. It kind of feels burning. But there's capsaicin patches that essentially, you know. over activates your receptors without causing that much pain and then it will exhaust them and you become kind of numb to the pain a bit and part of you people with neuropathic pain gets prescribed ah capsaicin patches and that seemed to work and similarly enough ah things like novocaine they block things like the placebo effects so you know there is Like I said, lot of research in Tupé and Pathways and we're just at the tip of the iceberg of how everything is so interlinked and interconnected. I'm also interested in the number of people who, like, sort of like genetically the people who can't feel pain, like what kind of percentage are we looking at? I know your study would be a bit more skewed because you're looking for such people, but how common are they who just don't feel pain? It's really hard to tell, to be honest. I've written a few papers on, for example, the R221W carriers, and there's some numbers in the literature saying that, you know, it's less than 1 % of the population, that there's, you know, a few hundred people, but all of these estimates, when you try to look for the origin of those estimates, it kind of gets... confusing and it's people referencing each other from different papers, but there's never actually like an origin of how many people there are. My guess would be, you know, maybe a couple of thousands in the world at best. It's, it is extremely rare. And I think because it is so rare, it's very hard to get a proper population distribution from it. But that's just one gene, I guess, like we spoke with the person who had sort of cannabinoid receptor issues that's due to a different condition. So I'm guessing that there's more than one pathway to feel or not feel pain. Yeah, yeah. Yeah, with a few thousand I that there is a few thousand people with genetic uh change that makes you insensitive to pain. For people with the RT21W condition, we only knew about 20 people and they're all related. And you can have an old lady as far as we know, she's the first documented case and she does have kids and grandkids, but they all refuse to be part of research. So... Yeah, there's, it's hard to estimate. And I think it's also with things like pain and invisible, you know, disabilities or invisible changes is that you could go your whole life not really knowing that you have that. My own granddad, had like a very low pain sensitivity. He used to change labels for the electricity going on. He used to fix cars with the car motor running. ah Like in the hospital, he did not feel any pain from any treatments. So, you he might have had something, but it was never documented and no one really caught it. You just reminded me of, I think, most brown parents flipping things on the hot stoves with their hand and stuff. And I'm like, how are you doing this? I tried to flip a roti or something with my hand. It just burns my fingers. All the adults across, no pain felt, standing in ovens, putting hot bread on there. Yeah, and then the kind of the opposite spectrum, you have people with chronic pain who don't necessarily know that they have chronic pain. They're one of the quotes that I best remember from working with people in Fibromyalgia is that one of them said, I only recently learned that the normal amount of pain someone should feel every day is zero. And you know, Hehehehe. Hmm. that's just their normal, isn't it? And, you know, everybody can't really speak for everyone else's, you know. talking about physical pain, right? Because emotional pain is a different story. Yeah. Yeah, can't see it. Nobody really knows. Yeah, for PhD students, emotional pain is never at zero. Yes, the other thing I ever go, goes below like 20, 20 % on a good day. uh Stress levels as well. It's another thing. Apparently some people don't feel stress. yeah. Wow, what a life. Well, you've got to feel a little bit of stress, haven't you? Because, know, I mean, okay, if you're not, you know, obviously not all the time, but if you want to be a little bit stressed, because then you can appreciate the times when you're not stressed. Maybe. Maybe we just need to all live, maybe I've just lived such a stressful life. It's just like. Life is only getting more more stressful. Yes, exactly. This is very true. And so I guess we've kind of delved into a bit of the genetics and kind of what kind of chronic pain is and different people's kind of maybe experiences. But back to maybe specifically your research, Anas, is there a specific piece of research that you've maybe you're in the process of doing or you've completed that you want to share, you think is particularly interesting? Can you take us through the start to finish of how that went? how you came up with the question, what was the question, what you did to find out that question, you know, if you're already there with the results or you expect the results to be. yeah, of course. So I research study that I'm just finishing up now included doing interviews with people, with neuropathic post-stroke pain, fibromyalgia, and diabetic neuropathy. So I talked a bit about how those conditions are quite different, but similar in a way that they're all neuropathic pain conditions. So my interest was in understanding the qualitative, you know, subjective experience of. living with those conditions in UK. things like the impact on daily functioning, uh diagnosis, treatments, how much the aggravatory diagnosis and impact on work and family relations, just to understand how, you know, all these people have chronic pain, but is one chronic pain equal to another chronic pain? And the results were quite interesting in a way that the diagnosis, particularly people with fibromyalgia were the ones who or most likely to say, I don't 100 % agree with my diagnosis. I feel like I'm over something else. And probably had the most difficult time getting diagnosed. In UK, our guidelines do state that a GP should be able to diagnose a person with fibromyalgia, but most of the time to get referred to physiotherapists, rheumatologists, anywhere except the GP who can get diagnosed after maybe 10 appointments in like five years. It's not great. Whereas people with post stroke pain and diabetic neuropathy because it comes from a specific medical condition and the link is kind of known. They are a lot more likely to be diagnosed a lot faster, particularly with diabetes. With post stroke pain, it's still fairly rare and fairly unknown that it still gets missed in stroke clinics. And, you know, there's these interesting cases where, you know, some people are getting a lot of support for their pain to have support groups. They have uh accommodations at work and other chronic pain groups that don't have either of those things. And things like diabetes and post-stroke pain, it often comes with some physical signs, physical disabilities, difficulties walking. Whereas some of them with fibromyalgia, they may not appear disabled at all. They might not appear like they're in pain at all. And that way is the sort of strange, you know, very real condition that is essentially invisible to everyone except the people who are suffering from it. And the results are, you know, are still coming out. I'm still finishing up the analysis. We've done interviews with 75 people, which is a lot for a qualitative study. And we're using sort of AI, we're using an algorithm called topic modeling that is able to essentially take transcripts and identify the most common words that come up from those interviews and the most common themes. So essentially having the AI to do thematic analysis for you and you can double check it. uh You find codes to support those teams. And I will also be working with, well, I am working with um someone who is running a support group for people with chronic pain. And so anything that comes up, want to check with her to make sure that it reflects her experience, it reflects experience of people who are in that group and that I'm not just coming up with things and saying, so this group feels that way. You know, there is a famous quote saying, no research about us without us. And I'm a big proponent of that. And I want this project to really embody that. That's incredibly interesting. um Like you said, I'm not surprised about the fibromyalgia patients because as you had said before, it's not just very hard to diagnose. It's also very, yeah, like the pain is very different in terms of where it is. Like you said, for post-stroke patients, you said that it's usually on the right side. It's usually the arms. It's a lot easy. um So is there anything which you've noticed so far? I 75 interviews is a lot of interviews. Like usually people say we did a qualitative study and it's 12 people. So I know you're going to do the analysis and all that info detail, but are there any themes here already picking up on which you think will come out? Um, life is not great, especially in UK. I think, well, you know, I think UK is advanced a lot of things and I think there is a lot of world leading research into chronic pain, but there's still a lot of issues for getting adjustments of work and lots of people having to quit work because the adjustments don't go far enough. And there is a very real lack of public awareness about chronic pain. there is this. sort of perception that if you don't look disabled and you don't have a disability. ah I know that, you know, more recently there's been things like the sunflower lanyards for mental health conditions that have been raising awareness of invisible disabilities. But it still is the main thing that people have said. And it was the same across all three conditions. You know, things like your friends not knowing what's happening, your friends not knowing why you're canceling when even though you don't appear like you're in pain, your family. properly understanding it. And I think just lack of support groups in general as well. not only is the general public not really understanding, but we need to hunt down people who are hosting support groups. It's still a postcard lottery. ah You know, some areas have quite a few support groups for things like stroke or fibromyalgia. Some places don't. And even in those groups, is marginalization. With post-stroke pain, It usually happens in older populations, but then when you're 20, 30, 40, you feel very excluded because suddenly you're in a room with a lot of people who are over 60 and they have lot of different issues than you who, you know, you feel like you were robbed of your, you know, let's say prime years, you you were, you're grieving your prime years because you had a stroke at 20, you had fibromyalgia at 20 and you know, it creates this kind of distinction between people who are in the groups who might be who the groups are targeted towards, like older people with stroke, and then you come in and you don't really know how to help you. So like just a discrimination that's different levels from society, from your community, from doctors. Yeah. I mean, those are the people who, like you said, probably be most affected by the whole work thing, right? I mean, if you're most likely to get a stroke in your 60s, you're probably retired or towards the end of your careers. if you're, like you said, 20, 30, 40, and then you have a stroke, you have chronic pain, not able to work. The sympathy also garnered by the general public is also very little considering they can't see it. Yeah, that's right. think that's why I wanted to do this research, just to raise awareness. And that's why, you know, I try to do some public engagement around invisible disabilities in general, just to, you know, let people know that they exist. And then when someone develops fibromyalgia or, you know, FND that you've, that I've do some work in, it's not, my God, what is this? You're not just given a diagnosis and let go from the doctors. You're like, think, okay, I have heard of this before or someone I know has this. So it's not scary because there are some resources out there. I somewhat know about this, but if you're just going to diagnosis of fibromyalgia, you don't know like, is it terminal? Is it curable? Can it ever change? And you know, it's kind of the same for the other chronic pain conditions. There is not enough information. The doctor just tell you. desire medication. Have fun. Hopefully it will work. Yeah. And I guess most of the medication as well is just sort of like kind of alleviating that pain for a little bit. you said, one, they're not very effective and two, they're not necessarily improving our sort of functioning over a period of time, are they? It's not like you're getting better. It's just that you're sort of maintaining. Yeah. m if you're lucky to not get any side effects as well, uh like I mentioned, the most effective medication is types of antidepressants, at least for post-stroke pain. And they're not designed for pain, they're designed for depression. And lot of antidepressant medications, they're known for side effects. So some people just cannot go on medication because the side effects are unbearable. So the ones who don't get the side effects, they're... lucky enough. think if you get medication and you can take your pain down to a level where it doesn't bother you too much and you can get on with your life, you've essentially won lottery in the very rare majority where you can somewhat get on with your life. Yeah, makes sense. Has there been quite, do you think, a change in way people view fibromyalgia and functional neurological disorder, especially within the healthcare system? I feel like when I've spoken to people a while ago, they maybe felt like they were dismissed a little bit, or it's not a real disorder, maybe because you can't see it and there's not always a m specific pinpoint of where the pain's coming from. Yeah, definitely. think with the advent of neuroimaging and pathophysiological findings, we kind of have an idea of what causes fibromyalgia. scientists are, and doctors, they want to think of themselves as very rational, but they also will not believe something unless there is like very tangible proof. So you can have someone saying to them, I have pain, this is a real condition, they'll just... say, no, you know, that's what happened with female hysteria. had all these women saying something is really wrong and doctors going, no, you're just hysterical. know, with fibromyalgia and the recent research, now know that there's a few hypotheses, one of which is pain centralization. So a theory that more functional of the central nervous system creates and augments pain that is not attributable to any other that identifiable damage or inflammation in the body. um so essentially the pain system is augmenting secondary pain of, you know, potential underlying chronic health conditions, or it just, um, due to overactivity of it, the, there is more and more pain neurons that become active. The more you have pain, the more your body is sensitive to pain, the more receptors you have. And then you just. kind of spirals into the cycle of in the end, your body creating pain for you. And there has been some research into the potential um cause of fibromyalgia through inflammation. So with, for example, COVID-19, we saw an immune system creating this cytokine storm, um where these inflammation molecules cause localized pain that can overwhelm the whole body. these cytokines, they essentially are a body's way to... fight inflammation, but it can also damage the pain receptors and pain neurons, which, you know, it can lead to damage in pain areas we already talked about, like in the thalamus or ACC. And they can also, you know, create change in different ways. Going outside of MRI, have EEG proof that fibromyalgia exists. In uh fibromyalgia, saw that there's a decreased low frequency waves, so delta, theta, and alpha, and increased high frequency waves. And that essentially means that with low frequency waves, if you have a lot of them, it kind of indicates relaxation, reduced anxiety. So in pharmacology, have the opposite, ah no relaxation and a lot of anxiety, and increased high frequency waves that indicate ah processing and heightened awareness. So the body is... struggling to relax and it's bombarded with anxiety and at the same time they have a heightened awareness to the pain that's coming out of their body. How does that sort of differ from the other pain conditions which you've mentioned in terms of what it looks like on EEG and fMRIs? Because I'm trying to think of like how would you distinguish between sort of fibromyalgia and others through EEG fMRI? I think that's an area of research. There has not been a lot of EEG research into central post-stroke pain. And there has not been any EEG research into pain and sensitivity conditions. So I really cannot say, but I would like to see people do EEG research into this. We have been trying to get a project off the ground that would look at EEG of central post-stroke pain and then also capturing those EEG waves. uh, as we're doing TMS. So, you know, the lab essentially created a way to use TMS and then capturing changes in brainwaves. So we can kind of in real time figure out how TMS works because at the moment we still aren't completely sure. And that would also, you know, give some basis for the HE readings of post-trogpain, but it's something that's in the pipeline and You know, hopefully my supervisor won't kill me for talking about it. Fingers crossed you get it. I'm sure Andy will be fine, maybe. I guess that kind of nicely leads on to my next question. So I want you to pretend you've got the biggest budget that any researcher has ever been given. And there's no such thing as the ethics board anymore. It's gone. It's just not a thing anymore. This is not true, by the way, everybody. What would be, was there a study that you would do? You could do anything in the world, anything. there's anything that you would want to do. research into catamine and magic mushrooms of course, but for science. size of course, of course. No, I think I would really like to do more research into TMS and MRI. So as I mentioned, we don't necessarily know how TMS works and a lot of it is probably placebo. There has been only a few successful sham controls of TMS just because there's a lot of things happening to it. You feel a sensation in your head, you hear a sound, it interacts with your brain areas. And it's very hard to replicate that sensation. I had it done on myself. I was a little test bunny. And sensation is essentially someone kind of like doing this into your head. And it's hard to replicate it in a way that uh the participants actually feel it. And then at the same time, you can't really do it in an MRI lab most of the time because TMS compatible MRI machines are super rare and really, really, really expensive. So, you know, I would like to do a proper research where TMS is used for pain with a proper sham coil and used in an MRI scanner to get sort of real-time data of the exact differences and how, you know, what placebo is activating in the brain and then what additional areas are activated by TMS. Theoretically, because I, when you're saying TMS, I mean, you talk, I assume you're talking about the treatment, not that we don't know how TMS works. We're more talking about how TMS, like, sort of helps alleviate pain. Or do we not know how TMS itself, how it works? Now it's like a hot topic in uh research to be honest. There's a lot of naysayers and there's a lot of yaysayers on TMS because like I mentioned there's been a real struggle to replicate it with a placebo. A lot of people think it's a full sham and just a hundred percent placebo so we are still trying to understand how it works. I mean, there's talk about that with the fMRI as well, right? I remember this paper from ages ago about fMRI, like, what do you say, being able to detect activity in dead Atlantic salmon. uh favourite papers. I literally share that one I'm like teaching about why we have to be careful with like false positives. Yeah. Did you see that paper with AI where tried to classify, I think it was dementia? And you got almost 100 % classification rates? I think it was dementia. It was a neurological condition and an AI was fed brain scans from someone with dementia and someone with just healthy controls. And you got 100 % identification right. only to realize that the dementia cases had a small number at the bottom because it came from a human connectome project. So the AI was just looking at the small number at the bottom of the scan and correctly identifying brain spread outs. I mean, that's, it's, there's all these things, yeah, that I mean, why we, I think AI is incredibly important, but there is, there's definitely like, yeah, things like that. I would just have to double check that what's being fed into it isn't, yeah, it's actually. That's the thing, right? All these things are only as good as the information you feed them, right? Yeah. And if it misinterpreted as well, just as an example, and we had a lab meeting yesterday and, you know, this one of the students came in and said, I found this great presentation where I feed it a paper and then what I wanted to do and it just spits all out and gives me a beautiful presentation. And we're great. And we're about to start. And she was like, it's actually putting a lot of wrong information, so I'm gonna have to present next week. you know, it's actually a bit like good that she checked it, but it was absolutely, you know, it does misinterpret some of the things. So good to put in, but then having like a check once over, I guess is like, you know, the most important thing. I'll have to give that a read, aren't I? So that is, yeah, that is a great, great example of, Speaking of AI, one of the courses at my university now, what we do is, one assignment is we get AI to write an assignment. We get chat with GPT to write an assignment with references and then we give it to our students, we like correct what's wrong in this. So we're like, it's done. Chat GPT has written this, correct why this is wrong. Most of it is because like, chat GPT makes up its own references, but there's also other absolutely bizarre things which it says. Yeah, massively. And that's actually a really, yeah, that's really helpful way. I have to suggest that to some of the people here, maybe. I I think Beth, you know about how if you, you know, ask AI for help with coding, sometimes it loves to either make up things or, you know, if it's very specific and you know exactly which forum post it took it from. And then you're just like, I saw the exact same forum post, Mr. HIGPT. You're not smarter than me. No, I've been there, I've been on Substack, I've been shouted at by some of the people on there. Well, mean, you know, keyboard warrior on it, you know, I've been there, I need you to help me. You know, it's the dichotomy of research. can either go on Substack and get an actual result, but people shout at you, or you can go to HHPT, don't get an actual result, but you can shout at someone. So, you know. oh Which side of their history do you want to be on? um Back to your research though, Anas. I want to talk to you a little bit about your participant experiences now. We spoke about the qualitative stuff, but suppose I'm someone coming in to get the MRI. done with you. Sort of what is that experience like? ah And sort of what are you in particular looking for? Because I think we've covered just generally things, but in sort of your experiments, what is the particular aim of these ones? Yeah, we try to keep the participant journey as smooth as possible. know, saying that I do inflict light pain onto them, which I definitely do not enjoy now. uh So the MRI scan itself, it's quite long, it's about 45 minutes. um As Bob probably knows, it does get very noisy in there. Some people manage to fall asleep, other people are in a bit of a state of panic. Yeah. But when you are in the MRI scanner, we have these goggles that kind of go on, well, this mirror that goes on top of your eyes. And you can kind of see either into the control room or out behind you. So if you're really claustrophobic, you can kind of see people there who are taking care of you. And we have all these different adjustments in the way that your head rests. So we try to make it as comfortable as possible. We do a task MRI where we inflict light pain onto the participants. So a heat pain of seven out of 10 with a thermo in their hand that heats up and it causes the pain centers to light up that we adjusted before to go in the scanner so we know what is subjective temperature for them is. So seven out of 10 for one person might be 50 degrees for another might be four to five. We really tried to tailor it so that it's very individualistic. And then when we do some sensory testing afterwards, again, making sure that we're not hurting them. So our machines have the limits of how high we can go and how low can go. And similarly, if someone says that I'm in 100 % pain, in 10 out of 10 pain, we have to stop and just shut it down. And that does happen sometimes. Not because it's particularly painful, but when it comes to people with neuropathic pain, they are so hypersensitive that what for us might feel like 10 out of 100, for them feels like 100 out of 100. And we obviously did not want to traumatize them or hurt them. So we, you know, take their word for how painful it is and we just stop it. And through all of that, you know, like I've mentioned that there's particular areas of the brain responsible for different things, the homunculus, and we're uh looking at a specific area called Rodman's 3A. So it's an area that's responsible for vibration and pain. It's right in the sulci. And it's been found in some animal models to relate to neuropathic pain, and particularly from c-afferent. So c-afferent neurons are neurons that transmit slow signals. So you have high signals, uh and you have high signal neurons and slow signal neurons. So the fast ones, if you get a paper cut, tape mule trials to your spine, you get a reflex arc, you pull over immediately. With the CF variants, it's more of long-term pain. And that is related to the BA3A area. And we're trying to localize it through applying vibration motor, the scanner, and then applying the heat pain to hopefully get that exact brain area to light up. So then we can create a pain connectome of how the pain travels from uh their arms to... legs or the side of the body that hurts into the thalamus, how it travels to the B.A.3 area, tend to the humunculus and understanding really which part of that pathway is overactive and which part of the pathway is the one responsible for pain. We do contrast it with non-neurophatic pain. So after a stroke, lot of people get spasticity, they're unable to move, so to get pain from cramped up muscles. And we compare them with neuropathic pain to really understand what is neuropathic pain and what are neuropathic pain pathways versus what are just physical pain pathways. Yeah. Do you think there's any overlap between these two pathways? Or do you think that, I mean, I guess they all run through the Talamus one way the other. um Um, I couldn't tell you off the top of my head exactly how different you are, but I think with the pain and sensitivity cohort, it did show that, um, you know, the motor reactivity to pain travels through slightly different pathways. So that is a bit more physical because they're, don't want to move away from a physical pain. So they're oh You know, the research that we found from uh their cases, it kind of helps to inform and formulate this project. It, you know, lets us know what to kind of expect. So with them, was primarily the spinal pylomic pathway, the pathways that are more responsible for movement rather than pain. So I could kind of expect that in the physical pain cohorts, we might see more movement facts being involved rather than specific pain tracks in the. uh sensor cortex. That's really, really interesting. And so I'm just trying to think that once we know like where this pain is coming from, oh what can we sort of do next? Is the next step sort of finding therapeutic treatment? So is it sort of, like you said, like TMSing and sort of seeing that if we can cut this off, will pain change? What do you, as someone who works in this, what do you think is the next step? I think the two main outcomes that we're hoping to get is that if we're able to identify the exact areas of the pain pathway that are implicated in causing this pain, can create, um again, going back to AI, can create an algorithm that can identify people who might be at risk of developing that pain. So everyone after a stroke, they get an MRI scan regardless, just because it's standard NHS practice. So with that algorithm, we can apply it to all stroke patients and identify someone who might be at risk of developing pain because that pain develops about two or three months after your stroke and not immediately. So we can start on the treatment pathways as soon as possible. And the very start of your stroke journey is what determines a lot of the future outcomes. But we will also hopefully use it for TMS. At the moment, we use TMS primarily on the motor cortex. an area of the brain that's responsible for movement and not pain, which is a bit counterintuitive, but we do it because those cortexes are very interlinked. know, the humunculus is the same, they relate to same brain areas. But with the motor cortex, we're able to know that we're targeting the exact spot because we get a bit of movement. So if we target your fingers, you get a bit of a twitch. And if someone is having pain in that area, we know for sure that we're targeting that area. with, you know, if we can identify an area that's really responsible for pain, not just the general hand area, like just the specific area causing pain in the hand, that will hopefully optimize the outcomes of treatment. Very nice. I said, yeah, very, very needed. And you said it comes two to three months after stroke. Why two to three months afterwards? Why not straight away? We're not exactly sure. You know, it could be due to diagnosis. diagnosis criteria is, you know, I'll say not super known to a lot of stroke clinicians. A lot of stroke clinics, they're not as versed in post-stroke pain and they might not be confident in diagnosing it until it gets seen by a third or fourth clinician. So some of the cases might just be missed. and they're diagnosed two to three months later. Or some cases might just be, you know, as your brain is making new connections after a stroke and trying to retake function that was lost in one area, those new connections suddenly make overactive connections that relate to pain and other things. So it could be a side effects of neuro generation. That's interesting. Yeah, it really interesting you said that because it is like, you've got like two or three months where you could really try and stop it from you're going to that neuropathic pain. It's fascinating. Because we've been recording for about an hour, I should ask Arnas, are there any sort of things which we've spoken about so far, or which we haven't spoken about so far, which you'd like to say, share, ask for the last 10 or so minutes before we end? I think you wanted me to share a Hot Take about my research. ah dismissed, we've put quite a few hot takes in throughout from your hate of chiropractors to... what we tend to do is I am I will ask them, we we cut the clip down for like 20 seconds. I like this. OK, if I ask the question. Is that OK? here. uh honest, do you have a research hot take for us? ah I do. I believe that fibromyalgia is invisible to everyone except people who have it and researchers. I think that is because, you know, it goes back to you saying that it's essentially an invisible illness, an invisible disorder that unless you're suffering from it, you don't know how much pain someone is in. Unless you're using an aid for walking, you will not really know that they are in pain. you know, the society, your friends, your family, they will not know how much you're suffering. And a of the time, neither will your GP. And... You know, there are clinical guidelines that state that GPs should be able to diagnose fibromyalgia. 99 % of the time it is not the case and it gets missed by GPs, uh neurologists, rheumatologists and physiotherapists. The reason why I said that it's usually not missed by researchers is because that's kind of our bread and butter that, you know, we seek out people with fibromyalgia. We want to uplift their voices. want to spotlight this condition. Whereas a lot of other... clinicians, know, they will, they're more interested in figuring out that there's nothing wrong with you in a physical sense, that you're not having heart problems, you're not having stroke, you're not having cancer, and they sometimes just don't think about fibromyalgia and don't diagnose it and just kind of leave people to fend for themselves with pain. It's very low down the sort of like checklist of this is this is this. Yeah, okay. He's breathing. He's this is that. Okay. looks all right. All limbs are in place. You get to go. ah No, awesome. ah Then if that's the case, I'll ask one final question, which is more general as well. uh So, four, do you have any advice for us and our listeners? So if you had one piece of advice to give us and our listeners, what would it be? If someone is in pain, believe them. People are very unlikely to fake pain and fake disability. Even in cases where we have seen where people think they're symptoms, they are so incredibly rare and they make up such a small minority of all cases that by not believing someone, we're actually harming 99 % of the people who are half their life impacted, turned around and who had their life taken away from them. So we should always believe people who are suffering, be it with mental health conditions, uh pain conditions, or any other physical disabilities, because no one knows their body better than they do. Not their GPs, not their ah therapists, not their physiotherapists. The only person who knows your body best is you. Awesome. think that's great. Very fad words. No, it wasn't on that note, we can end this episode. So thank you so much, Anas, for coming on. Thank you, everyone. That sounded great. and thank you everybody for listening so until next time take care