Show Notes

In this episode world renowned fibromyalgia researcher Professor Dr. Kati Thieme shares her research and understanding about the root cause of fibromyalgia. She tells of how her theoretical research accidentally led to the discovery of an effective treatment for fibromyalgia called Systolic Extinction Training (SET), which when combined with psychological brain-training strategies, is very effective in resolving chronic pain in fibromyalgia and other conditions.

Professor Dr Kati Thieme explains how blood pressure and baroreceptor sensitivity relays to the autonomic nervous system (ANS) in the brainstem via the NTS nucleus, and how this part of the brain becomes 'blind' to the data from the body leading to dysregulation or dysautonomia as well as chronic pain.

We discuss heart rate variability in this context as well as problems around fibromyalgia research and why a tailored approach to recovery is required, plus much more.

Timestamps

Transcript

00:00:02 Dan

Systolic extinction training.

If you have fibromyalgia or related condition, you've probably never heard of this, but is that all about the change? In this episode of Wisdom from the other side, I speak with one of the world's most decorated research scientists, specializing in finding effective treatment options for fibromyalgia and other chronic conditions. Perhaps some of you recognize the name Professor Doctor Kati Thieme.

So, are we on the cusp of seeing a highly effective treatments for the wider global patient community? I loved her story of how she accidentally discovers a treatment during her research. 

<<INTRO AND SNIPPETS>>

00:04:39 Dan

Hi Kati, thanks for coming to join us on Wisdom from the Other Side.

00:04:43 Dr. Kati Thieme

Yeah, thank you very much for your invitation, it's a pleasure.

00:04:49 Dan

Well, I have been a connected with you guys and looked at your research for some years now and today we will obviously focus on your work on systolic extinction training and of course most of our listeners won't know what that is and we will go into some detail, but before we do, I want to ask you, you've been a medical researcher for many years now. You've been highly decorated. I know you won the International Fibromyalgia Research Award in 2008. You've won many national awards in Germany and so your work has been on chronic pain. But at some stage she started to focus on fibromyalgia and I wonder why is that?

00:05:40 Dr. Kati Thieme

Fibromyalgia, it's very interesting disease for me, because it shows us how stress can influence our body and can change so called inhibition processes in our body that leads from actually a healthy, very active state to a diseased state. Yeah, so there's a high level of impairment interference, and yeah, sometimes lower activity, sometimes extremely high activity because the people don't feel the pain so much when they are in a stress situation. Yeah, and it and it it has so many different phases. It's a very interesting disease. Yeah, and I like the people.

00:06:30 Dan

You know it is complex, isn't it? And I think that's probably part of the reason why the wider research community, medical community have struggled with this illness because not only is it complex, but the patient community is. It's heterogeneous, right? It's not that everybody is the same, and you know just before we started. You did mention that there was an interesting difference between the patient groups around the world specifically in America, how people are trying to get away from the word Fibromyalgia syndrome. Can you sort of recount to us? What that was all about?

00:07:11 Dr. Kati Thieme

Yeah, I observed a very interesting discussion between the patients that have some support group in US and in Germany and in US it is so that the patients say that is fibromyalgia and now the fibromyalgia is a syndrome, because a syndrome is always something where symptoms are not connected with each other, right? So, in Germany, patients say, OK, it's fibromyalgia syndrome.

00:07:38 Dr. Kati Thieme

Yeah, I'm actually thinking. when you see the global or central symptoms of fibromyalgia like sleep deficits, pain, fatigue and essential impairments like cognitive concentration and memory deficits. They are connected, they are actually clearly connected. And maybe we can talk later about this connection.

00:08:06 Dan

Absolutely, and I think this is really what connected us in the very first place some years ago and really the thing too is like, I mean, one of the things I often see patients saying is, how can I be so unlucky? You know, first I have irritable bowel syndrome and I have chronic fatigue and then I have fibromyalgia and then I have POTS and then I have, you know it goes on and on and on and they feel they've got so many different diseases.

00:08:38 Dan

But absolutely you can see that when you really look at it, there is this underlying connection between all of them, and I think when people can understand that, it takes a lot of the stress and worrying away, don't you think? Yeah, have you found that with your patient education that this becomes a very important part of their journey is that they start to understand what's going on, that it helps them feel more at ease and more relaxed?

00:09:07 Dr. Kati Thieme

Yeah, because it's always the case that this kind of complexity of symptoms makes the people crazy. Yeah, they think they aren't normal anymore. They doubt in their own perception. It must be a very difficult situation. So, when they learn that all these symptoms belong together and have a clear connection, yeah, so we start for example in the patient education.

00:09:36 Dr. Kati Thieme

It's a very easy question. I am asking, what do you think when you hear that word pain? Yeah, then they start with brainstorming what they think about this. Maybe yeah, the pain is something that is disturbing, it interferes my daily activity. I try to lay down or I'm thinking, that is so bad. Why do I have this disease? What have I done?

00:10:12 Dr. Kati Thieme

Yeah, so or it's just this kind of sensory description how the pain feels so and then I sort all these different answers, and then we see four folders like four phone calls, yeah so and each folder, is clearly connected to brain areas.

00:10:36 Dr. Kati Thieme

Yeah, all the sensory impressions that pain gives us is connected to the somatosensory cortex, right? So, and all these sorts are connected to the prefrontal cortex. The emotions that I feel sad or helpless or sometimes angry is connected to the amygdala or to other centers of our emotions in the brain. And then we found out that we have also something else that is actually now in the in the discussion in the pain field, if that belongs to the pain network. And this is the brainstem. Yeah, and the brainstem influence some components to the autonomic nervous system.

00:11:29 Dan

You know, obviously one of the great battles that many patients face is that have all these weird symptoms. Now some symptoms can be easily measured, like if they have hypothyroidism or they have abnormal cortisol rhythms. When you do sleep studies, you know all these types of things and a lot of the time, a standard blood test is not gonna necessarily show anything and people get, you know, it's suggested like it's they're just depressed or it's in their heads. There's nothing wrong with them and this type of thing.

00:12:04 Dan

And so, I find it very interesting that, you know, I mean, your background is actually in psychology, and yet you make a very strong and clear argument that this illness is not psychological. And I love how that, really bridges the gap between the mind and the nervous system, because it seems people always look at these things as being separate, but obviously the mind, the nervous system and the body, I mean these are all connected, right?

00:12:34 Dr. Kati Thieme

Yeah, yeah, of course. So, my argument belongs to this, uh, incited psychological disorders like, mood disorders or anxiety are learned disorders, right? So learned by cognitions, maybe provoked by external situations. Yeah? Or learned by influences by parenting, for example. So, and here in fibromyalgia, it's more biological learning. Yeah, so maybe I can tell you a little bit more about this, how it works.

00:13:12 Dan

Yes, absolutely.

00:13:13 Dr. Kati Thieme

Yeah, so for example patient is in a stressful situation for a longer time. Yeah, I remember a patient. She was the boss of 2000 people in the warehouse. Yeah, so and she, from her personality she is a person who tried to be corroborative with all the colleagues. Yeah, and had trouble when some people responded with the question, for example. Yeah, so it means it's a lovely lady, actually. And she did a great job but, sometimes other people can be pretty aggressive and can provoke stress in our life, right? So, and she tried to be more friendly. Tried to explain to people why they have to work on this and this way and so on.

00:14:13 Dr. Kati Thieme

So whatever and she came in this situation that was very stressful for herself and the situation turned out that her husband’s said to her, please stop working there. Change your job. Yeah, so she doesn't want that because she didn't want to lose this fight also, right? So, it's completely understandable. The work was going on in her body. She was in a very stressful situation.

00:14:45 Dr. Kati Thieme

Her blood pressure went up and as the blood pressure learned not to vary anymore, because she was not able to be relaxed because it was always in effect, right? This is a very complicated situation and because the blood pressure couldn't vary anymore the pressure intensities in the carotids developed to be very stable. This sounds actually not too bad, but it's fatal for our body because we have baroreceptors in the carotids and these baroreceptors block only when the blood pressure intensities vary, because as soon as the blood pressure intensity goes up so that means the pressure intensities in the carotids go up.

00:15:35 Dr. Kati Thieme

Then the baroreceptors relay to the brainstem the information, something is going on in the body, please regulate. Yeah, so and when our pressure intensities don't vary anymore, then the baroreceptors don't relay the information to the brain stem so it means the brain stem or the brain doesn't know what's going on in the body and doesn't regulate. Yeah, so and we have a very little nucleus in the brainstem. The abbreviation is NTS, and this NTS has a function to regulate pain, blood pressure, sleep, Uh, catecholamines as stress hormones, anxiety and even blood sugar.

00:16:28 Dr. Kati Thieme

And this nucleus is also connected to different areas of the pain network. Yeah, so it means when the brain stem doesn't regulate, our amygdala as it is responsible for our emotions, cannot regulate because it just doesn't get the information. Yeah, and so we saw in our EEG, the tests and examinations that when a patient, a fibromyalgia patient gets pain stimulus the response from the brainstem and the somatosensory cortex is much, much later and lower than in healthy people.

00:17:15 Dr. Kati Thieme

And normally is it so that, that in the very first 50 and 100 and 150 milliseconds, the brain gets information, oh there's a pain stimulus, right? So, and later in about 260 and 400 milliseconds, our emotions and our cognitions respond, right? So, we saw in this EEG profile, that the somatosensory cortex and the brainstem doesn't realize what's going on, but, just in the consequence, the emotion and the thoughts were extremely active, yeah, and so it explains why our fibromyalgia patients have these kind of doubts, sometimes anxiety and depressive mood or affective distress at least. Yeah, and also these kind of catastrophizings, yeah? So that explains also that we have many, many opportunities to break through this circle, yeah, this devil's circle and have many opportunities to influence the pain.

00:18:31 Dan

Fascinating, yeah, thank you for detailing that. You know you. You talk about the blood, the blood pressure variation, that the baroreceptors sense, and obviously, there's a blood pressure variation I guess with every heartbeat, right? So, when you talk about variation, uhm, I mean that variation is still there. So can you sort of explain how it varies then with people as they get into distressed state. Are you saying that the difference is just smaller between the systolic and diastolic or what exactly do you mean?

00:19:08 Dr. Kati Thieme

Actually, when the people come in a stress situation, the systolic blood pressure went up, right? Not so much the diastolic, actually. The systolic blood pressure, right? So, and then the patient comes back in the relaxation and the blood pressure goes down. And only when a patient is for a long, long time in a stress situation, also the diastolic blood pressure learns to go up. Yeah, that's why the cardiologists say always when the diastolic blood pressure is higher, then the heart has learned not to be relaxed anymore. It just loses the ability for relaxation.

00:19:58 Dan

And so, when you say that there is less variation in the blood pressure, do you mean the change in blood pressure in relation to stimulus? Like if somebody is being stimulated through stress or pain that it doesn't change as much. Is that what you mean?

00:20:11 Dr. Kati Thieme

Yeah, exactly.

00:20:13 Dr. Kati Thieme

It's a situation that, uhm, the healthy body is adaptive to the situation so it means when you are in a stress situation, your blood pressure goes up and now the stress situation is over and you can relax.

00:20:27 Dr. Kati Thieme

Yeah, we see that very, very impressively in kids, right? So, they are active the whole time, and we, as adults a little bit stressed out so and then they sit down for, I don't know, five minutes and we will know now she's tired. How nice. Just a time for five minutes, and then she's active again, yeah? So, in the last example and you can see here, these people in this situation. It can relax.

00:21:05 Dr. Kati Thieme

So, in this relaxation state she can consume energy, and or he can consume energy and is very active afterwards, so in when our body is not able anymore to go in this deep relaxation, so for example when our sleep is disturbed, then this variation that the blood pressure goes down during the relaxation situation is not possible anymore, yeah?

00:21:35 Dan

Well, it's interesting. I can't help but reflect. Now obviously your patient group that you focus on is fibromyalgia. Yeah, while I focus on all the different patient groups, including chronic fatigue syndrome, which I consider to be in essence the same illness. And when you look at the heart rate variability, it again shows that there is a low heart rate variability, which suggests an inability of, now I know a lot of people are suggesting it, that that means you know it's in the sympathetic response, but I think a better way from my point of view is to say it is not able to express a parasympathetic response, which is exactly kind of what this, what you're saying here isn't it?

00:22:18 Dr. Kati Thieme

Yeah, it's completely right.

00:22:18 Dan

The body just can't quite calm down.

00:22:21 Dr. Kati Thieme

Yeah, that's completely right. So, we have two terms. We have the variability of the heart rate and we have the variability of the blood pressure, and this heart rate variability has much more intense research than the blood pressure variability. So, and we learn from the heart rate variability, that exactly this problematic disbalance of sympathetic and parasympathetic nervous system can create a disease or disorder. Yeah?

00:22:53 Dr. Kati Thieme

And we see this mechanism in many, many chronic diseases. And when you come when you come back to the NTS, then you see that all the global diseases like hypertension, chronic pain, sleep disorders, diabetes, anxiety disorders, that all these global diseases have actually the beginning in the dysregulation of the NTS and the baroreceptors.

00:23:25 Dan

I'd like to just sort of go back a few steps. You know, we were talking about how we have a lack of variability in blood pressure or lack of responsiveness, let's say, and how that obviously impacts via the baroreceptors to the NTS and then it goes to the rest of the network in the brain. And you drew the conclusion from that how that the timing of the blood pressure sensing translates into a delay in the pain sensing. Can you sort of talk a little bit?

00:24:10 Dan

Because most people who listen, will say, well here we're talking about blood pressure, now we're talking about pain. How do they come to overlap? How does that connection happen?

00:24:20 Dr. Kati Thieme

Yeah, actually in healthy people or beings even also in animals we have an inverse relationship of blood pressure and pain. So, it means maybe our patients can remember before they developed a pain disorder and they have received an acute pain like headache or teeth. Yeah, so and then the normal situation is that that we think "oh no, I don't want that. Yeah, I don't need it." It is kind of catastrophizing is coming up as first probably yeah. And also the emotions.

00:25:02 Dr. Kati Thieme

Oh no, this is not nice, yeah so. It's just a little bit anxiety or anger and maybe also a little bit depression. So, and then at the same time, in a high subgroup of us, yeah, so more than 50 percent, the blood pressure goes up, and as soon as the blood pressure goes up, the baroreceptors are activated, right? Because the intensity, pressure intensities is going up and so the baroreceptors are awake and they send the signal to the brainstem,

00:25:38 Dr. Kati Thieme

Brainstem regulates and the blood pressure goes down, yeah, so the pain goes up and then the blood pressure goes up and the pain goes down. And this is this kind of inverse relationship in healthy beings, people and animals. Yeah, and as soon as we come in the situations that we have for long term stress in our lives, we develop the risk that the pressure intensities go up.

00:26:15 Dan

So, you mentioned obviously that there is this variation and how people's body responds in healthy population or in the fibromyalgia population and I know you did some research looking specifically at the autonomic nervous system dysfunction that people have with fibromyalgia and found it goes into different subgroups. Right?

00:26:37 Dr. Kati Thieme

Yeah, yeah.

00:26:38 Dan

Yeah, and I wonder how can we work this out? How can we have the same issue with the barosensitivity reducing and creating pain even if we don't have high blood pressure? Some people have low blood pressure, right?

00:26:54 Dr. Kati Thieme

Yeah, so yeah, we did a stress experiment and this stress equipment had two stressors. One stressor was mental arithmetic and one stressor was a social stressor. So, we asked the patients before the experiment, related to their partnership, what are the problems that you discuss with your partner? And what are the problems that you don't discuss with them?

00:27:26 Dr. Kati Thieme

So, and then during the experiment, we have invited to partner too, we ask both what is the reason that you don't discuss this topic? Yeah, so and this was, extremely an extremely high stress for all of our patients because it was so, you know, I mean actually I could bring a lion in the room, yeah so and this was inappropriate stressor because we couldn't find any differences between our patients anymore.

00:27:49 Dan

Confronting.

00:28:00 Dr. Kati Thieme

It was just too much. So, my experience is that social stress is really what makes us sick. Yeah, so in mental arithmetic as stressor allowed to find the differences between the patients and we found four different responses.

00:28:19 Dr. Kati Thieme

Interestingly, the same responses that we found years before with patients with rheumatoid arthritis and systemic lupus erythematosus as inflammatory rheumatic diseases, patients with hypertension, patients with chronic depressions or psychiatric disorders. And also in healthy people. We have tested astronauts and cosmonauts, or very healthy people, and so it seems these four different response patterns are really valid in our human responses, yeah.

00:28:59 Dr. Kati Thieme

And the most important or the major stress response was the response with high blood pressure, followed by the response with low blood pressure, so until we differ between baseline and reactivity and we see that people can respond with a high blood pressure in baseline these are clearly our hypertensive patients and they can also respond with, also normal kinds of blood pressure, but as soon as they come in a stress situation, they go up and respond with hypertensive blood pressure responses.

00:29:36 Dr. Kati Thieme

Yeah, so in the second group that you mentioned before, is it so that people can have a hypotensive blood pressure as the baseline and also in normal tensive, but can go down in stress situation. Yeah, so and the interesting thing is it provokes also this kind of stable pressure intensity in the carotids, and that reduce also the baroreceptors.

00:29:54 Dan

Right yes.

00:30:07 Dr. Kati Thieme

Or reduced activity of the baroreceptors. Yeah, gradually we can always awake them. Yeah, but as soon as people is in stress situation, the procedure is the same. That baroreceptors just sleep. Yeah, they don't work anymore.

00:30:28 Dan

That's very interesting. You know often. You know, we see that we have in this, if we look at the patient population a little bit more broadly than fibromyalgia, and we see the especially the category who starts to get the low blood pressure and obviously less variability, but they don't necessarily develop the pain syndrome, and yet they still get all the other things that are part of the illness except the pain and, I sort of wonder, yeah, they get the fatigue or they get the tachycardia attacks, they get the anxiety. They can come on all through the NTS, that same network, except the pain doesn't seem to come on. And I wonder, you know, why is it that with them the pain doesn't become so prominent, even though they still have this lack of variability in their blood pressure?

00:31:30 Dr. Kati Thieme

We see an interesting phenomena and we call that stress energies, and here it also, again this kind of very interesting close relationship between psychosocial adaptation and between biological learning and so, for example, Dennis Turk found out years ago that we can respond in three different psychosocial adaptation types, and one type is the so-called interpersonal distress type.

00:32:04 Dr. Kati Thieme

And that means that the people, as patients mentioned, that partner doesn't respond so positively to their disease, mostly negatively or even with punishment. So, like, that they don't respond when the patient is in trouble with the disease, or that they don't support or that they don't say any nice thing.

00:32:28 Dr. Kati Thieme

They are mostly stressed out.

00:32:30 Dr. Kati Thieme

We found that these partners mostly suffer by themselves with depressive and mood disorders, you know. And that's why they are not able to respond with empathy, but so that leads to the situations that the patients of fibromyalgia or fatigue patients think, " I shouldn't show so much that I'm in pain."

00:32:59 Dr. Kati Thieme

So, and to avoid this kind of negative responses, they start to be more active that they can tolerate, actually. yeah, so and that provokes new stress. And interestingly, these patients have a very a high activity of the so-called mu opioid receptors.

00:33:26 Dr. Kati Thieme

And these mu opioid receptors provoke the stress energies so that means, in contrast to other patients with the same disease, if fatigued or with fibromyalgia, they don't receive so much pain, or to be correct, they perceive less pain as soon as they are in stress situations and so they experience the stress situation as wellbeing because they don't perceive so much pain, or they perceive less pain. So, in this perception of feeling better, as soon as they are in a stress situation is a huge reinforcer for our brain. It's like a reward. Yeah, wellbeing is always the strongest reinforcer, it’s a reward force, right?

00:34:26 Dan

Absolutely yeah.

00:34:33 Dr. Kati Thieme

So and so it comes automatically. This has nothing to do with our conscious mind is just an unconscious, we call it upfront condition learning and as soon as you are in this situation, you try to come back in this kind of wellbeing situation. And this explains why this subgroup of our patients are so active, so extremely active.

00:34:56 Dr. Kati Thieme

Now I remember a patient, a young lady, and she said actually, I don't know if pain is my first problem. I feel more fatigued and I'm not so strong anymore and I don't know why. And I'm also aware that something is wrong, probably at the evaluation of her own strongness, and I doubt that despite any reasons and they ask her, tell me a little bit, what is that, what you, what you do over the week, right?

00:35:37 Dr. Kati Thieme

So, and then she told me that she has two kids, one of the kid is mentally retarded, this other one, this other gift is highly gifted. Those kids need a lot of special support. Yeah, for their mental needs. Then they built their house. She has her father-in-law at home and the father-in-law has Alzheimer's, so it means they have pretty often visits from the police because he's running away and they have to look for him. Then her own mother has dementia and she has her mother in a senior hospital, but she tries to visit her three times a week, because she doesn't want the mother to forget her, right? So, and she is working full time, and her husband too. You know, and this is a moment when I was thinking, wow, I couldn't handle this.

00:36:58 Dan

Well, I mean, if we took her and made her somebody who was a bomb diffuser in the Middle Eastern warzone, she would probably experience a stress reduction from her symptoms, right?

00:37:13 Dan

OK, look so.

00:37:16 Dr. Kati Thieme

So, and one point. Oh, it's just a second, it’s essential. When she would leave all these kind of task to fulfill, she wouldn't be able anymore to relax. Yeah, because she is so adapted in this situation that she would feel guilty when she would say no, I can't do that anymore.

00:37:41 Dan

Relaxing is a complicated thing and it's not an easy thing in my experience with seeing people recover from fibromyalgia, CFS and POTS,

00:37:49 Dan

I would say that the number one thing that stops them is their inability to just back off, and show themselves some kindness and give themselves a break and it's quite surprising because in chronic fatigue syndrome people make a strong connection to post exertional malaise, so everyone knows, hey, if I do too much, I become sick. And yet, our ability to not do too much, it's very, very, difficult for people and they keep getting caught and they don't progress in their recovery because of this.

00:38:30 Dan

And so, I wonder, you know, why is it that people have this, find it almost impossible to just stop? And give themselves this time to heal and recover. What do you think it drives that?

00:38:50 Dr. Kati Thieme

Yeah, I think this is an automatic process, right?

00:38:56 Dr. Kati Thieme

So, for example, when we take the second subgroup we have, so there is hypotension, but actually can do almost the same as with hypertension. And then you see their experience, when they do more, they have less pain. So just what is the consequence? They do more. Yeah, so in the hypertension group, so when they do less, they have less pain for that moment right? So, and then they do less. So, until the body learns it won't go to do less, and then it's a circle to do more, yeah, but both leads to the situation. That they do not have so much physical tolerance. Yeah, they cannot tolerate additional tasks by different ways, of course.

00:39:51 Dr. Kati Thieme

And so yeah, and what we said before the consequences that the variability is not given anymore. So that means the brainstem doesn't know actually what's going on in the body. And then the NTS doesn't regulate anymore, how should the body be able to be relaxed? This is not possible, yeah?

00:40:19 Dan

So really what, If I can paraphrase you, what you're saying is in one group, we're doing too much and therefore we can never gain rest and the other one we're not doing enough, and so we become deconditioned, but both of them lead to the reduction ability to do things, right?

00:40:35 Dan

And obviously the nervous system that's supposed to regulate our ability to respond to stressors, if that doesn't go up and down, that kind of reflects that, doesn't it?  Because it's supposed to be rest and digest, we're supposed to come down so that we recuperate, and then we can do things again, but, with the baroreceptor NTS pathway being sort of, I don't wanna say flatlining, 'cause that sounds too negative, but let's say, not very variable, there's no power for rejuvenation in the body.

00:41:07 Dr. Kati Thieme

Actually, this is not wrong. I mean when we made our first test was baroreflex sensitivity, we saw, this was in North Carolina in 50% of our fibromyalgia patients, no baroreflex anymore. Completely flat. In the first point we thought our technique was damaged.

00:41:30 Dan

It's broken. You need to get new equipment, where is your engineer?

00:41:34 Dr. Kati Thieme

Then we considered the group of healthy people, and here everything works, everything was fine.

00:41:46 Dan

OK, so in the moment we're going to start talking about reversing this and obviously the brain is plastic. We can go one way the brain can learn to do these silly unhelpful things and the brain can learn to function more normally again and obviously that's your focus, neuroplasticity and normalizing. But before we talk about this mechanism, I just need to ask this. I said this, I think before we started when I wrote my book and I came up with the hypothesis, and as I neared described this as reinventing the wheel, right? but, everywhere we looked it was still said that,

00:42:28 Dan

the cause of fibromyalgia or the mechanism is a mystery and I remember at the time reaching out to some pain researchers and saying, hey, have a look, I think the ANS is a central component of this central nervous system dysfunction and this pain sensitization, and I got kind of a very skeptical response. Yet, it appears to me that there is a lot of evidence for this, clear evidence, that this is what's going on.

00:42:58 Dan

I mean what would you say is the most, one question in two parts. One, what is the most compelling evidence about this and two, do you think that the research community is moving towards a consensus, and recognize that this is what's going on?

00:43:14 Dr. Kati Thieme

Yeah, I think, you know, these responses, as you have gotten is probably related to what we call the medical history mystery. Yeah, so it means in the 1st place that people had to learn or we had to learn that pain perception belongs actually to the central responses, right? This is our brain, so it means we make experience independent on the level of damage, we can feel different pain.

00:43:51 Dr. Kati Thieme

Yeah, so the next step is now to see what is the influence of the autonomic nervous system and what is the relationship with the central system. It means we have a lot of researchers and physicians and also psychologists and physiotherapists who have to deal with the idea that pain is not 1 to 1 related to the level of damage.

00:44:20 Dr. Kati Thieme

Yeah, I mean when you consider all these kinds of not so useful surgeries, right? Back pain, for example. So, it means this is really a clear topic and then the next thing, this experience what we had with the fatigue syndrome or with fibromyalgia, it's not a psychiatric disorder. So, it means these neuroscience insights helped us to convince patients and professionals. That is, it's not a psychiatric disorder and the damage is not responsible for the intensity of the perceived pain.

00:45:04 Dr. Kati Thieme

Yeah, so and now the second thing is to find out what are the relationships to the autonomic nervous system, right? And in this disturbed or diminished inverse relationship of blood pressure and pain, yeah, that was actually described in 1994, in the [NPAS inaudible]  on a very high ranked journal by colleagues from Tubingen, together with Barry Dworkin, who work in the Karolinska Institute right now. Now these colleagues described very intensively this kind of diminished relationship, inverse relationship, of blood pressure and pain.

00:45:57 Dr. Kati Thieme

But normally, insights need at least 50 years ago, many people see that, or recognize what's going on. And the thing is, because no money was given to the research for clinical trials at this time, so in the 90s, they just described it for healthy people, and they mentioned that people with chronic disorders have a diminished inverse relationship, but only right now is it so that we are working on it, that this diminished inverse relationship is actually kind of a clear suggestion of the relationship of autonomic nervous system and the central nervous system.

00:46:51 Dr. Kati Thieme

But it's hard to believe for many people, yeah, and of course we have this kind of impressive heterogeneity, so it means the research has a task to select, right now, we have from the methodological point of view, these ideas that RCT studies or randomized clinical trials, so it means randomized, not selected. Yeah, it has a higher standard, right?

00:47:18 Dr. Kati Thieme

But on the other hand, we have the idea that's individualized treatment has the highest chance to heal or to make our patients feel better so it means we have here different approaches that fight the illness with each other.

00:47:42 Dan

Absolutely and this is one of the points I keep making, this idea of how do you do a clinical trial when the treatment is supposed to be different for the people in it?

00:47:53 Dr. Kati Thieme

Yeah, yeah.

00:47:54 Dan

I mean this this doesn't make sense, right? And the other thing is that my concern is with these kinds of studies, and you know, I've had a look at setting up a study for ANS Rewire, is well, how do you then measure it? And what do the outcomes mean?

00:48:11 Dan

Because you know people will then often draw conclusions and in medicines people often talk about responders, non-responders and partial responders, but if I were to get a proper scientific study of, let's say, a sample of 100 people, 1000 people, and I would say, OK, well these people responded great, partial and no non-responders, but that does not necessarily reflect the approach. You could really ask the question of why did those people not respond, as opposed to saying it simply doesn't work for them because I think at the end of the day, it's still the same disease, even though we see these differences, right?

00:48:49 Dan

So, and obviously somebody who's got a history of PTSD and a person who has diabetes or hypertension, leading, before they had fibromyalgia, you need a different treatment, right?

00:49:00 Dr. Kati Thieme

Yeah, yeah. Of course.

00:49:03 Dr. Kati Thieme

You need also a different approach regarding the medication, right? So that means we already have a lot of medication who provoke the diminished relationship between blood pressure and pain, who provoke this kind of diminished baroreflex sensitivity.

00:49:22 Dan

So, are you talking about beta blockers and things like this?

00:49:25 Dr. Kati Thieme

Yeah, yeah.

00:49:27 Dan

Yeah, is there any other sort of medications that do so?

00:49:32 Dr. Kati Thieme

Yeah, we saw in the psychiatric field, for example, anxiolytic or antidepressants, or even medications that I used for treating hypothyroidosis.

00:49:59 Dan

Hyper or hypo? Hyperthyroidism or hypo like high thyroid or low thyroid?

00:50:08 Dr. Kati Thieme

I guess it's high. No, it's low. I'm sorry. It's low.

00:50:10 Dan

Hypo.

00:50:11 Dr. Kati Thieme

Low yeah, right?

00:50:12 Dan

OK, yes.

00:50:13 Dr. Kati Thieme

I'm choosing about my patients right now. So, yeah.

00:50:17 Dan

OK, right. Interesting.

00:50:19 Dr. Kati Thieme

So and of course, you don't know which patient is responding with a reduction of baroreflex sensitivity when they get these medications, not everybody is responding this way.

00:50:40 Dan

So, I think it's the natural for us to talk now about affecting positive neuroplasticity, right?

00:50:46 Dan

OK, and the brain loses its way, we end up in this state of dysfunction, and we talk about reversing it, and I guess this is where in your research, you started to work on systolic extinction training, and in a moment, I'll get you to explain what systolic extinction training is, but I have to tell you part of me wondered, how did they come up with this?

00:51:12 Dr. Kati Thieme

Yeah, I mean this one, well, it's actually an interesting experience when I worked in North Carolina with Rick Gracely and Bill Max now. We actually wanted to find out what is the meaning of the baroreflex sensitivity for the fibromyalgia patients, right? So, we moved from earlier studies that always when we give stimuli after the systolic peak, we will reactivate the baroreflex sensitivity. So, and we were thinking, ok, we have to check that again we have to test this.

00:51:53 Dr. Kati Thieme

And the best control condition is when we give the stimuli also after the diastolic. Yeah, as a control condition, right? So, and then we wanted to find out if it's really true that the central response is different when the stimulus comes immediately after the systolic peak or after the diastolic. We made an EEG experiment. And then we sought a visual test also, if it makes a difference, if a patient gets a pain free stimulus or a pain stimulus. So, in our own early studies we saw that our brain doesn't learn when the brain gets, or the body gets a stimulus that is 50% of our tolerance, of or pain tolerance, but it learns when it's 75% or even 100% of our pain tolerance.

00:52:58 Dr. Kati Thieme

So, 100% was not allowed because of ethical reasons. So, we selected 50% and 75% in comparison to pain free stimulus. So, these three types, they're given immediately after systolic or after the diastolic beat. So, we made those, yeah. And then the first patient said, "I was sitting here for 8 hours and I feel better. What have you done?" Yeah, so and I thought, I don't know. I really don't know.

00:53:39 Dr. Kati Thieme

And then I thought maybe we had a good talk in between and maybe we like each other and I don't know so, but then the 2nd and the 3rd patients said the same and this third patient said, "Can I come back? Maybe my brain learns it." So, and this was the beginning of the treatment. So it means, actually our intention was completely different. We just wanted to find out what is the response of our brain. Yeah, it was a very theoretical approach, actually. And in the end, we found a treatment and had to explain what we did, that's funny, right?

00:54:17 Dan

So, did you find that both groups responded like with the stimulus after systolic and with the two different groups, one after systolic, one after diastolic?

00:54:27 Dr. Kati Thieme

No, we saw that from the central responses, the brain responds only after the systolic beat. Yeah, that's the interesting thing is, and when we give only stimuli after the systolic beat, the brain adapts and cannot learn anymore. Yeah, so when we give it also when we when we bring the brain in this situation that the brain gets also stimuli after the diastolic peak, it doesn't provoke reflex, then the brain has only to learn.

00:55:09 Dan

Interesting, so is it

00:55:11 Dr. Kati Thieme

It's like an intervention, you know, in the gym.

00:55:14 Dan

Yes, yeah. I see what you mean, but so is the idea that when you give the pain stimulus at the systolic, is it that it creates higher peak? Does the pain create an increase in the blood pressure in that moment, and is that why we are getting this baroreflex sensitivity?

00:55:37 Dr. Kati Thieme

Yeah, and it's of course a probably more mechanical thing, I mean, the systolic means the blood goes from the heart directly into the carotids, right? So, if diastolic, means it goes in the body. Yeah, so and when the blood goes directly in the carotids and we give stimulus, at this moment the pressure intensities are changed in the carotids.

00:56:07 Dan

Fascinating, so you're talking about, that it works at higher thresholds. Is that because do you think it is because there's a bigger increase in the blood pressure or could it be because it creates a greater level of focus in the brain because in neuroplasticity focus is really one of the main factors to affect positive neuroplasticity, right? And nothing like getting really good focus as getting a bit of a zap.

00:56:44 Dr. Kati Thieme

Uh, we are in the beginning with these questions.

00:56:49 Dr. Kati Thieme

The only thing, what I can say is that when we give the stimulus after the systolic beat, we provoke this baroreflex, a reflex right? A biological reflex on the brain so when we give it after the diastolic, we don't do that. So, it means this is just this kind of life condition, what the patients experience, unfortunately, every day when he or she gets pain.

00:57:15 Dan

Obviously, this was a surprise, and researchers like that, isn't it? We do things and we discover things that sometimes we don't expect. Did you have many other moments during your years of fibromyalgia research where you stumbled across something and go, wow I didn't expect this?

00:57:34 Dr. Kati Thieme

I think it's so that, this kind of intuition probably works after you have worked in different fields in the research that leads to exactly this result, right?

00:58:01 Dan

Yeah, I mean did you ever have any other sort of moments where we just surprised at what you found? Doing your usual research where you just went "Wow, I really didn't expect that to occur"? Did you have many moments like that?

00:58:11 Dr. Kati Thieme

I mean this is this is mostly the case in the treatment. Yeah, there's many of these moments, and then also for example, we have started also to treat our patients with opioid addiction, right? So and we saw when we give them the stimuli stimulation twice a week additionally to the psychological pain treatment, it didn't help. And the patients told us, when I get the stimulation, within three hours, I feel much better. And then, 6 hours later I feel so worse.

00:58:58 Dr. Kati Thieme

So, and we were thinking about this and try to find out what is the reason for that. And then our hypothesis was, maybe, it's because the brain hasn't learned yet.

00:59:12 Dr. Kati Thieme

And it hasn't learned so it means maybe this kind of opioid endogenous, opioid and cannabinoid system, has started to work and then it rushed. Yeah, so and so it means they need more, just more.

00:59:34 Dr. Kati Thieme

And so, we started to present the stimulation every day and in the first patient we had to find out for, what kind of time. Yeah, and the patient reported after 12 days or 12 stimulations they are free from opioid addiction.

00:59:56 Dr. Kati Thieme

Yeah, this was also a very important moment because usually I learned, we need at least 12 weeks, we have to reduce the doses of the opioids, yeah, so that the patient doesn't know about this, yeah, and have to be focused on distraction and wellbeing and so on. Yeah, and the patient shouldn't make so many pain protocols so that he isn't focused on it, or she, yeah.

01:00:29 Dr. Kati Thieme

So, and here we have 12 days and now we have developed these treatments that we say, OK we make 12 days every day, also over the weekend and then, we start with this kind of three times a week and later two times.

01:00:49 Dr. Kati Thieme

And we started in patients with neuropathic pain because of, paraplegic disorder.

01:01:02 Dan

Yeah, paraplegic.

01:01:04 Dr. Kati Thieme

Once they have this kind of neuropathic pain that is a phantom pain, so it means in these areas of the body that are actually paralyzed. Yeah, so they have a huge amount of medication and so we could see that they could reduce medication to 80, 75 to 80% and could reduce the pain, to the amount of which is the intensity of the numeric rating scale one and two.

01:01:43 Dr. Kati Thieme

Yeah, so an anesthesiologist will start only this medication when they have more than three. Now so it means, in contrast to the problem of the patient, they don't lose the pain, but it's so low that they don't need this kind of very intense medication.

01:02:05 Dan

Because opioid medications don't necessarily work on all fibromyalgia patients, right?

01:02:11 Dr. Kati Thieme

No.

01:02:14 Dan

In fact, would it be fair to say they don't work on most fibromyalgia patients, can we go that far?

01:02:24 Dr. Kati Thieme

You know, I have problems to give these kinds of global conclusions. We like to see the patient, and I have a very low number of patients who have for them, opioids or cannabinoids. It's very low. I can remember almost only in two patients; I've been through more than 4500. I mean you can try, but when it doesn't work anymore then you should stop immediately, yeah?

01:03:05 Dan

Look, as we actually sort of start to draw towards a conclusion, I guess the obvious question people will be asking is you know, how effective is it for people 'cause being a heterogeneous group, one would expect that it wouldn't work for everyone or it wouldn't work the same for everyone. And I know that the systolic extinction training doesn't work in isolation.

01:03:30 Dan

It was so you work with the other more, let's say, traditional factors that influence pain, psychological factors. So you do some operant conditioning. I mean, how effective is this training? And can people expect this to start getting this kind of treatment from their doctor?

01:03:55 Dr. Kati Thieme

Uh, so the thing is when the people suffer from hypertension, they have the highest effects. Yeah, because this hypertension shows that the body is able to increase the blood pressure.

01:04:11 Dr. Kati Thieme

Yeah, so and that means when we give these stimuli immediately after the systolic and diastolic peak, we can influence the blood pressure intensities, and so we can reactivate the baroreflex, yeah and this cord of NTS reflex arcs. Yeah, so this is this is for sure, but it works only in combination with the psychological pain treatments.

01:04:34 Dr. Kati Thieme

So, it means that when the people and the patients learn, this is my pain network, and I can influence the pain by changing my catastrophizing thoughts to adaptive coping, changing my pain behaviors to healthy behaviors. Yeah, and we learned when patients get only the stimulation, they break up after three or four sessions.

01:05:04 Dr. Kati Thieme

So, it means that it's an actually a strong suggestion that we have really a pain network. Yeah, and that means we need to influence all the components, not only the brainstem.

01:05:19 Dr. Kati Thieme

Yeah, we need to influence the prefrontal cortex by changing our thoughts, the amygdala and the brain areas that are responsible for our emotions, and also somatosensory cortex for example, by relaxation, so but to do just one, it's not effective. We need to do all of them. Yeah, to influence all of them, also because it can really interact and they interact with each other, yeah, and so we have to come from very different sides there to be stronger than this little devil.

01:05:58 Dan

Well, it makes sense, doesn't it? I mean, the brain is complex. And if you look at, you know pain, I mean it's not like 1 little part in the brain that operates for pain, right?

01:06:12 Dr. Kati Thieme

No, no.

01:06:13 Dan

It goes all over the place, right? It lights up like a Christmas tree so of course it makes sense that you need a multilateral approach. What about physical treatments? Have you looked at physical treatments in combination with this training, because there's obviously physical stressors that impact the nervous system also.

01:06:36 Dr. Kati Thieme

Yeah, we made bike training. Yeah, so and combined this with the baroreflex sensitivity training, And we saw for the first time actually that physiotherapy can provoke responders. So, it means 14% of our patients could reduce the pain to 50%. Yeah, so this is the first time because mostly physiotherapy has short term effects, it has to be, right?

01:07:07 Dr. Kati Thieme

I mean, it's actually the nature in us, right? So, when we've made sport in our childhood, it doesn't mean that we are pretty sportive also when we are older, right?

01:07:22 Dan

We don't stay fit forever, right?

01:07:26 Dr. Kati Thieme

Right so we have to activate this everyday so at least, twice a week.

01:07:35 Dan

Yeah, yeah.

01:07:37 Dr. Kati Thieme

And that means here was the first time that this was a long-term effect. So, it means 12 months after the treatment, right? So, but it's not the same effect when you combine the baroreceptor training with some psychological pain treatment and provokes a pain freedom for a long term.

01:08:00 Dan

I want to just talk a little bit more about the psychological side of things and because I feel like this is, 1, misunderstood by the patient community, but 2, I feel like it's misunderstood by the psychologists, by the treatment community.

01:08:18 Dan

Yeah, yeah, right and even though I think the research community has actually understood these psychological mechanisms for really quite some time, so one of the things that I've been very frustrated about is when I came up with the explanation, the program, the book, and I was seeking, I was doing patient advocacy and one of the things I was talking to people about with fibromyalgia is go and see a pain psychologist, and my focus was so that you seek to effect changes in your brain and you make a recovery.

01:08:59 Dan

But when they went to see pain psychologist, they learned coping strategies and management, but all the language was geared towards just being able to live with pain better. And my message was always, no, your focus should be on using these psychological techniques to get rid of the pain.

01:09:18 Dr. Kati Thieme

Yeah, yeah.

01:09:19 Dan

But it seems like there's always, that the patient community didn't like this idea, because it suggests that the pain was like psychological, which we're saying it's not. And I felt like the community, even pain psychologists didn't want to say that because they were afraid to make claims that they couldn't fulfill.

01:09:40 Dr. Kati Thieme

Yeah, and also, the people are different and many people rush to become pain free, but then they are so under pressure that it has to be fulfilled. Yeah, and this pressure provokes so much stress that it's actually counterproductive, right?

01:10:00 Dr. Kati Thieme

So that's why you have to find out what is the best way. I mean one way is also there are some people or some patients who could become pain free, each body is different. We have to find out what is possible.

01:10:16 Dan

And the best way is to try.

01:10:18 Dr. Kati Thieme

Yeah, just try.

01:10:20 Dan

Just try it. Yeah, but I think it's important to try with a positive expectation without the pressure.

01:10:30 Dan

Now one of the things in the psychological side of things we speak about, obviously there's a range of things that can affect our pain perception. Attention, anticipation, and also, the meaning of the sensation, right?

01:10:47 Dr. Kati Thieme

Yeah, yeah.

01:10:49 Dan

These are the three core ones that I focus on. Do you think there's any other core factors that influence pain perceptions aside of those 3?

01:10:56 Dr. Kati Thieme

Yeah, also reinforcers, right? So, for example, we see in partnerships that have a high empathy level, that understandably, the healthy partner wants to help this hurt partner, right?

01:11:12 Dr. Kati Thieme

This is normally it's nice and it makes this kind of healthy relationship, also very supportive, right? So, what I had to learn in the treatment is that our brain doesn't interpret the support as a support, it interprets that or misinterprets as a reward for pain. So, then the pain is going stronger because of the reward and it's repeated and repeated and repeated and then we have chronic pain. So, it means you have this intensity of this support and what kind of support, is it the support that things that partners, that a healthy partner would have given also, when the patient wouldn't be a patient?

01:12:02 Dr. Kati Thieme

Or is it a support that is defined by pain? Yeah, so for example, I remember a young couple from Spain, and we spoke about this kind of pain behaviors and how she shows that and automatically and how he responds. And she said, actually, it's it starts already when he comes home from work and he looks at me and said, how are you doing today? Yeah, so I mean this is very friendly right? But our brain misinterprets it unfortunately as, how is your pain?

01:12:42 Dr. Kati Thieme

Yeah, so and then I asked them, and how was it before you developed fibromyalgia? And then they thought, and then they said we were students. And when he came home, he said, do you like to order a pizza? And this was completely different, it has nothing to do with pain.

01:13:07 Dr. Kati Thieme

So, and this was a moment when they understood how to switch the approach and what they can do and what they can change. Yeah, so and then she said OK, so this is actually the idea, uh, to fake it until you make it. I said yes, exactly. Try. Yeah, so and so they found out we need to be focused on something that has nothing to do with pain, but it's necessary to have an agreement about it right? Otherwise, when the partners doing this without the agreement of the patient partner, then as a patient partner, she feels it as this is no support. This is this is negative. But when they agree with that, then they can really find completely new methods.

01:14:06 Dr. Kati Thieme

So, for example, another example, both wanted to come to make a bike trip, so because he liked to do that before she developed fibromyalgia.

01:14:18 Dr. Kati Thieme

So, and then we had to find out what is the best way to do it to avoid more pain afterwards, right? So, the first thing is not to think about the pain, otherwise, when you do everything because of the pain, then you have activated your brain network already. So, what can you do? We think about the other ways, what kind of trip we want to do and what is our goal and can we have can we grab a coffee there to reward our trip, yeah?

01:14:53 Dan

Efforts yeah, yeah.

01:14:54 Dr. Kati Thieme

Our efforts, so and maybe also piece of cake. OK, and so they are focused on this cake. OK, so and then the next thing was how can we provoke that it's a relaxed trip, and before, it was always a situation that he, because he was faster, was the 1st and she followed. Now we changed that and that she's the first, and he's following her, yeah, but his task is to say when they take a break because this is something that she cannot, not yet feel. Yeah, and so he decided, to make a break, and she reported later, yeah, this is true, I didn't feel it and it was good that he said that.

01:15:48 Dan

Well, this is particularly insightful, sorry to interject Kati, but I mean it also helps us get around the issue that, you know for us, when we obviously make a decision to protect ourselves from the pain and we engage in protective behaviors, I mean this is also unhelpful.

01:16:08 Dr. Kati Thieme

Yeah.

01:16:09 Dan

But at the same point, if we push beyond our barriers and create physical stress, that's also unhelpful. So, it's like this is where people think that, damned if they do and damned if they don't. And so, I love how they work together in the sense that he's the one who stops her from over doing it and she doesn't act in a way like an ill person, well she is ill, but she doesn't have illness behavior which contributes to the sensitization and it's really the perfect solution, is it not?

01:16:39 Dr. Kati Thieme

Yeah, yeah it is. And another thing is also mostly our fatigue and fibromyalgia patients are very, very active people, right? So, they are highly motivated. That's why I like them so much. And have a lot of ideas what they can do and so, but the thing is, this is something that we don't know yet,

01:17:05 Dr. Kati Thieme

We see that the perception of the muscle tension is kind of disturbed or became disturbed during the disease. Yeah, so for example when I asked them, please make a strong tension, make a very light and make a medium tension.

01:17:25 Dr. Kati Thieme

They have only trouble to find the medium tension, right? So, it means as soon as they are physically active, they go automatically, this kind of strong tension and this is too much.

01:17:35 Dan

All out.

01:17:37 Dr. Kati Thieme

Yeah, this is just too much and that's why the first step before we start with all the physical activation and so on, we just make the training of the muscle perception, yeah?

01:17:50 Dr. Kati Thieme

So, and it needs some sessions of until patient can do that.

01:17:51 Dr. Kati Thieme

One idea, for example is make a walk for just one minute as usually. You walk and count your steps. So, and your friend or partner or husband makes the same afterwards also for just a minute then compare the numbers. And then make the same with stairs, and count this and then compare and then make a calculation of minus 20%, and try to reach this new number.

01:18:37 Dr. Kati Thieme

Yeah, and then most of our patients have this feeling, oh this is so bad because it's some it seems as if somebody is holding me in the back. I cannot walk normally anymore and this is exactly this when they feel so tensed, right?

01:18:56 Dan

So, you're saying minus 20% in effort or tension in the muscles? Is that what you're saying?

01:19:00 Dr. Kati Thieme

No, no. in numbers.

01:19:00 Dan

In the number of steps.

01:19:02 Dr. Kati Thieme

They, for example, have 110 steps, and then they should walk on this way that they have just 80. Yeah, so it needs lower, right?

01:19:16 Dan

Right.

01:19:20 Dr. Kati Thieme

Yeah, so and mostly the patients make the experience that they have higher numbers than the healthy spouses.

01:19:30 Dan

Interesting.

01:19:30 Dr. Kati Thieme

Yeah, and exactly this is when we would say, the devil is in the detail, right?

01:19:38 Dr. Kati Thieme

So, when they are active, and they are, then the activity is too intense. The success is possible when the intensity is going down. Yeah, and then they can do more.

01:19:56 Dr. Kati Thieme

Yeah, like in the marathon training. Nobody trains a marathon. Most of the people train, I don't know, 5 miles, 10 miles or 20 miles most, yeah, but never the marathon and this is just only when the marathon is happening.

01:20:16 Dan

Well, yeah, I mean often talk to people in the program about this difference between work and effort. We think you know the work done is a finite amount, a fixed amount, but how much effort it takes to do that can vary, and it has to do with how we engage our nervous system.

01:20:32 Dan

I can lift something off make it easy, or "eeuugh", yeah, and I'm lifting the same weight but it feels very different, and inherently the difference is to why we're engaging our nervous system and learning how to regulate that is key.

01:20:46 Dan

And I've actually seen some people who recover who get so good at this that they almost become superhuman, you know? One lady, she became an ultramarathon swimmer. She goes in on a Monday and it comes out in other country on Tuesday and she feels like she can keep running. Because she's learned how to engage her nervous system. I've met many people with CFS who've learned these abilities.

01:21:12 Dan

Yeah, so it's just saying before I leave and look, I could talk to you all day and we must finish up. But I must ask this other question. One of the typical symptoms that we have with fibromyalgia is besides triggering of the pain, there are, for instance, times in in the monthly menstrual cycles for ladies where the pain gets worse, but there's also in the daily cycle. Often, we find in the late afternoon evenings the pain comes on and gets worse. Now both of those, in my view, are triggered by hormonal changes and in essence a sensitization, and I wonder how much have you looked into how the change in the in the cortisol levels during the day connect to our experience of pain and what is the mechanism there, do you think?

01:22:11 Dr. Kati Thieme

Yeah, I mean, this thing is actually very similar to the inflammatory rheumatic diseases, right? As pain is a big stressor whose body and we could see that uh, cortisol level is actually dysregulated in fibromyalgia.

01:22:36 Dr. Kati Thieme

And that goes along with a changed pain threshold, so it means there's a clear correlation between the cortisol and the pain threshold, and then the cortisol is down, then the pain threshold is down, right?

01:22:56 Dr. Kati Thieme

This has also something to do with our sleep. And we see, for example, that our fibromyalgia patients have enough deep sleep phases. Interestingly, this is what we actually haven't expected, because of earlier studies, but the thing is that these deep sleep phases are in the second phase of the night instead of the first phase of the night.

01:23:27 Dan

I wasn't aware of this.

01:23:28 Dr. Kati Thieme

So, and this belongs to this whole NTS reflex arcs, of course here, because this is not working so regularly anymore. That's why the sleep is dysregulated and that's why you have the deep sleep phases later. And these deep sleep phases influence our cortisol production.

01:23:51 Dr. Kati Thieme

Yeah, because in the deep sleep phase, your ACTH production is going down and when the ACTH production is going down, then the cortisol production can go down. If it's not going down, this is what the people feel as hyper focused, that they are going crazy.

01:24:11 Dr. Kati Thieme

You are in this kind of mentally overly active state and it leads to a state where over the time that your kidney is just overstressed.

01:24:29 Dan

The adrenal glands.

01:24:30 Dr. Kati Thieme

Erschöpft.

01:24:33 Dan

Yeah, exhausted.

01:24:34 Dr. Kati Thieme

Thank you. Yeah

01:24:36 Dr. Kati Thieme

Yeah, it's completely exhausted.

01:24:37 Dan

I know a few German.

01:24:41 Dr. Kati Thieme

And this kind of exhaustion, it brings the situation that the kidney cannot respond adequately anymore, and so the cortisol levels are going down. Yeah, next step, pain threshold is going down. Next step, pain intensity, pain perception is going up. Next step, sleep is disturbed because when the pain is going up, the blood pressure is going up, blood pressure doesn't vary anymore, so the baroreflex doesn't work anymore. The NTS doesn't work anymore, so sleep is disturbed and so you have this devil's circle, yeah?

01:25:21 Dan

So just in case I misunderstood here, I mean, are we saying, is it that the actual hormone level is low or is it the reason that the hormone level is low that is the problem? i.e., Cortisol is obviously an expression of the sympathetic nervous system, so I mean, is the issue with the pain perception? Do you think that the actual hormone is low? In other words, if we were to inject someone with cortisol, would that then not produce this evening hormone, not that you would want to do this, but would it then not reduce the pain levels? Or is it simply because it reflects the fact that our sympathetic nervous system tone has changed?

01:26:13 Dr. Kati Thieme

A second. A little bit too quick. So, the thing is, an expression of the sympathetic nervous activity is when the ACTH goes up, it provokes, the cortisol goes up, and then the ACTH goes down, right? So this is this kind of negative feedback loop and this is an expression of a healthy sympathetic response.

01:26:35 Dr. Kati Thieme

Yeah, but when this situation goes over a long time then we have exhaustion in the kidney, yeah, so, and then the ACTH goes up and the kidney doesn't respond adequately anymore, and so the ACTH stays. So, it means we have a higher sympathetic response over the time.

01:26:58 Dr. Kati Thieme

Yeah, so this is the first point and the 2nd is when the negative feedback loop is absent and the ACTH stays up, we have this problem that the blood pressure is mis responding. So, it means it goes up, but doesn't vary anymore, and then it provokes, the next circle with a diminished NTS reflex arcs and this influences sleep. And so, the patient doesn't have the opportunity to come in deep relaxation and so the higher ACTH production maintain.

01:27:48 Dan

Right, right. OK that makes sense. So, the higher ACTH production obviously stimulates the mineral corticoids and changes the sodium potassium balance. Yeah, OK, and we end up in a mess.

01:28:01 Dr. Kati Thieme

Yeah, and actually the question with the menstruation cycle, this is actually not yet clear what's going on there because there was a time when we try to find out if the sex hormones have any influence on pain because many women have pain right? And yeah, this is probably only one puzzle in the whole picture. So, I do not have so good explanations for that unfortunately.

01:28:34 Dan

Yeah, yeah. We still don't have all the answers.

01:28:35 Dan

Katie, people will ask, you know, will they be able to benefit from systolic extinction training themselves? I mean, is this a treatment that is likely to be available around the world at some time?

01:28:51 Dr. Kati Thieme

I hope so. Right now, we have a very expensive, lab, this is not possible to transport this to hospitals or practices also.

01:29:03 Dr. Kati Thieme

But we are working intensively on a smaller device and hope that we that we can get it ready to give to hospitals and to deeper practices and the psychological pain treatment is available.

01:29:24 Dr. Kati Thieme

But here's also this point that you mentioned before. Our psychologists have really to learn how to treat pain patients and to come away from this psychiatric approach and really to see, this is more of a training. This has nothing to do with psychopathology. This is a training, how you can use your mental abilities to be stronger than the pains.

01:29:52 Dan

Yeah yeah, yeah. Absolutely.

01:29:56 Dan

Katie, thank you so much for your wonderful insights and your fascinating research. And I love when I asked you the hard questions, you're able to come up with the with the answers, so it's very impressive. So thanks again for coming.

01:30:13 Dr. Kati Thieme

Thank you for your interesting questions. It's such a nice talk. Thank you so much.

01:30:18 Dan

Yeah, you're welcome, thank you.

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