The 9th Annual Pain Care Skills Training taking place at SOUTHCOM Conference Center of the Americas in Miami, Florida, brings colleagues and subject matter experts together to learn more about optimizing care and integrative approaches to pain management within the Department of Defense (DoD). The focus will be in sharing best practices, conducting hands on training and learning integrative approaches. The overall goal of the Pain Care Skills Training will be to promote readiness, restoration of function and relief of pain while decreasing the use of opioids.
Transcript
Please be seated. Now I’d like to introduce our host for the event, the SOUTHCOM’s Health Clinic Commander, Lieutenant Colonel Fred V. Torado to say a few words welcoming us. Thank you, Colonel Torado.
Morning. Can you guys hear me fine? On behalf of Colonel Danning, Dwight D. Eisenhower Army Medical Center Commander, and Admiral Craig S. Faller U.S. Central Command and Commander, welcome to the Ninth Annual Pain Care Skills Training here in beautiful South Florida. Today, we have the best of the best from all over the world sit in this room. Through the joint efforts of colleagues and subject matter experts, you will learn more about optimizing care, integrated and innovative approaches to pain management in the Department of Defense, where this is the number one priority and there is no other number one. Our people will always be our number one priority, because it is our military people that give us our greatest strength and our most important weapon system. We are the best armed forces in the world and what you in your daily lives to take care of our people, which is our soldiers, sailors, Coast Guard, Marines, Air Force, fallen members, civilians, retirees, and veterans, pays dividends to insure we remain the best armed forces in the world. Therefore, this week, let’s share those best practices, lessons learned, tag teams techniques and practices, to help restore functions and really pain, while mitigating the risk of drug addiction throughout our formation, families, and communities. It is not good enough to operate business as usual. We must treat our people with the best of the best because it is our people who deliver and support our readiness, organization, and reform efforts. Again, welcome to beautiful sunny Miami, so others may live. Thank you. (audience applauding)
Okay. So again, I wanna thank you all for coming here. We’ve had a lot of planning going forward and I think you’re gonna have a, I know you’re gonna have a fantastic week and we’re gonna start now with our first lecturer. So if you would go through our slides to the very last one. Um, yes. So, I put this one slide up, because this is our first, but we’re gonna have as our Anita Hickey Memorial Lecture. How many of you in here knew Captain Hickey? Oh, yes, a lot of people. So, I’ll tell you a story. Are you guys ready for a story?
[Audience] Yes.
I like stories. I’m a storyteller. So, I need you to picture it. This is early 90s, Boston. It’s snowing, right? Easy to picture now because it’s so hot out here. It’s snowing, right? Wine restaurant. What’s that place in Boston, you know? Where, I call them the ducks, the big ducks, but they’re actually, the swans are? You know, is it called The Commons? Or I think that the place, So I just finished that day. I gave Grand Rounds. Beth Israel Department of Anesthesia and Pain Medicine, and afterwards, they take us out to dinner, right? So we’re to dinner and we’re talking and things like that, and light nice time, lovely time. Fast forward a decade later. I’m sitting at BIU Med in a conference in a workshop that we’re doing, and I look over, and I’m like, “Mmm, that person looks familiar.” And then, those of you that know me, know that I have a memory of an elephant, so I walk over and I said, “Uh, 1990, Boston Beth Israel, “the Wine restaurant dinner.” She’s like, “Whoa,” and that was Captain Hickey, and that was when she was doing her fellowship at the BI in Boston, and since then, I had the pleasure of knowing Captain Hickey for many years. Captain Hickey was always a model for us on how the art of medicine incorporates with the science of medicine. Those of you that knew Captain Hickey, she would make time stop when she saw her patients, and those that worked with her in the clinic and her bosses said, “Hmm, we gotta speed up Captain Hickey.” I spoke to one of her bosses last night who said, “Make sure you tell them that she “was always the first doc that all of us bosses “would go to when we needed care.” So that’s my little story of Anita’s passed away this year? And this is the first of our annual lecture series for Anita, keeping her spirit alive. So thank you for listening from my little story, and now we will put our first. We will close out this slide deck and put our next series of slides on, and we have a big thank yous and lots of announcements that we’re gonna do at the break, and I have my Pain Fellows Extraordinaire who are also manning our slide decks. With that, I want to introduce our first speaker, our keynote speaker, Dr. Lewis. And Dr. Lewis is a neurologist. He’s currently serving at Brooke Army Medical Center. He’s a traumatic brain injury consultant to the Air Force Surgeon General. Dr. Lewis has been instrumental in leading the military health system Air Force Neurology. All of us in how we are looking at traumatic brain injury. Headache, neurology. He is also my co-chair on the upcoming headache clinical practice guideline, the DoD VA Headache Clinical Practice Guideline. Dr. Lewis, the minute I asked if he would come down here, he said, “Absolutely.” And when I asked if he would co-chair the Guideline with me again, he said, “Absolutely.” So with that, I’m gonna turn it over and I’ll welcome Colonel Lewis. (audience applauding) So, you’re not going to be able to control the slides, so just say, “Next slide,” and Adam over there, Nod to them there and they will post your next slide.
[Dr. Lewis] Okay.
[Chris] And this one is working right now, so unless you wanna walk around,
[Dr. Lewis] I think I’m gonna walk around.
[Chris] I’ll put this one up.
Can you hear me? Oh, yeah, I think so. I can hear me. So I have a habit of wandering when I present, so I thought rather than you all being subjected to me squirming up here, trying to move and stay close to the screen, I would move around a little bit with the microphone. It’s my privilege to be here today with you all and I really value being part of this and really having the privilege to present this first memorial lecture for someone who I didn’t get the chance to meet, but certainly appreciate the perspective that she offers when I read through the book that she had published, last night, and I think some of the points that she makes are representative of some of the material that we’ll talk about today, and that is, specifically, about pain in a broader context, but beyond just a sensory experience. So, I have no disclosures or anything to talk about financially, and then these are my views. And most of this material is really an evolution, so I’m trying to offer, sort of an insight as far as the state of the science, in terms of pain processing in the brain, and it’s evolving, it’s very challenging, and we certainly can talk about the limitations in trying to study the brain in a painful state, so I can offer some insights and will gladly share what I can here, but I set up, sort of three objectives, and that is to talk a little bit about sort of pain models, and then about some of the evolving science in terms of really neuroimaging for pain, because that’s one of the best ways to get at the human brain and pain, and then, to offer a little bit about how that can influence future treatments. So I like to start, and for those of you who I had the chance to meet a few years ago, I presented a Grand Rounds on Pain, and I began with this question about what is pain, because it’s something that I think is inherent in the human experience, but is difficult, I think, to clearly articulate what the full experience of pain is, and, So there are a few models and over time, they’ve evolved, so one of them is to look at pain as a sensory experience that has a neuro-anatomic pathway that’s very specific to a sensory experience and that’s a specific model. And then there’s also a convergent model, which is that pain is this integrated plastic state in which there’s a somato-sensory component, but then a whole lot of other stuff that also contributes to the experience, and that is what’s known as a convergent model, where you have lots of information that is converging along with the stimulus for pain to produce this experience that is plastic and changes over time. Next slide. So the specific model really dates back to the early 1900s where Sir Charles Sherrington developed the initial models of the senses. That’s there’s a teloreceptive, which is involved with vision and hearing. Proprioceptive, which is limb position. The exterosensitive or touch. Smell and taste, and then, visceral sensations were sort of divided out from the external exteroceptive, and being an interoceptive model, and pain and temperature, at least when I went through medical school, was considered part of this pain and temperature and touch were sort of co-lumped together in this exteroceptive model. And, at least, back in 1990, these were sort of the pathways that we talked about in the specific model. So we have the somatosensory cortex, which is involved with pain and temperature, and visceral afferents, which were then projected to a different part of the brain known as the insular cortex, which is sort of elegant cortex nestled inside between frontal and temporal and parietal lobes, and that’s really, The thought was that’s really where your processing of internal experience. When you’re hungry. When you sense disgust. That this part of the brain is activated, and they really were considered sort of two separate pathways for interoceptive and then exteroceptive information. But the model breaks down when you start to think about pain in the larger context, which was sort of, when reviewing the book from Dr. Hickey, I think that’s sort of the perspective that she had taken, is that there’s much more to pain than just this temperature and visceral sensations. There’s a huge emotional component. There’s a huge motivational component, and there’s influence on all sorts of aspects of cognitive function, particularly the area of attention, and that pain and attention. And I think most people would intuitively know this, influence each other and we certainly see that in our patients. What do we wanna explain very well by this exteroceptive model? So in trying to understand a broader context, the concept of a neuromatrix came forward and this really was propelled by experiences of providers taking care of their patients, and particularly in the area of phantom limb, where, you know, you really have lost the exteroceptive mechanisms for pain, or even sensation in the body, but that the pain persisted, and also, the sensory experience of retained limb would be there, and not only in patients with phantom limb, but patients that were born without limbs could describe this, and even as you started to dissect or resect parts of the brain that would be retained, parts of the brain, specifically involved with the exteroceptive. So the idea, sort of evolved, that there’s much more to the painful experience than just the initial sensory phenomenon. So in the human brain, we do have some ways to probe and look at the brain in a specific state, and some of the advances and the different modalities that we can use sort of propelled a search for this, this neuromatrix. So particularly in the areas of positon emission tomography, EEG, functional MRI, and magneto encephalography, sort of allowed us to look at the human brain in the painful experience and non-painful experience for comparison, and look at certain patterns, and the idea was that there is some sort of that particular pattern that would correlate with the painful experience, and that it wasn’t really necessarily any one specific location, that there wasn’t a pain center in the brain, but rather, the activity in the formation that would be correlated with the specific pattern of activation would be a pain signature, and it really has, until fairly recently, really has driven a lot of the efforts to understand pain, at least the neural correlates of pain, with the idea that once we understood this pain signature, then we could try either to influence that or use that as some kind of biomarker for pain. And so, scientists, physicians, and clinical scientists have developed a number of ways to try to use these tools to develop what characterized this pain signature, and we do that in a few different ways. One way is place people in a scanner and using thumbnail pressure or temperature, look at the activation patterns with a bold functional magnetic resonance imaging, or you can use radio bi-gens and PET and with that activation. Also, activation in the chronic pain patient just sitting in the scanner themselves, and what you see or what we see, and sort of characterized in the mid 2000s, was that its activation from many regions of the brain, and there are some that we wouldn’t be too surprised, with thalamus, and somato-sensory cortex, back to the exteroceptive model, but then there’s activation of the frontal cortex and activation in posterior, sort of integrating cortex down in brainstem, and insula and amygdala. So activation without this, and so this was sort of the model that had evolved in that, okay, so this pain signature is this pain matrix of all this different areas of activation in the brain that are all working together to produce the painful experience, and I highlighted here in red some of the areas that were most consistent. So anterior singular cortex there in the front, insular cortex and somatosensory, so these were the areas that seemed to carry through the most robustly in states in chronic pain patients at rest, and then also those with induced pain. So that’s led to evolution of this idea based on activations in insular cortex and others of this idea of pain, temperature, and visceral afferents all coming together very early on in the process and rather than just being out in sensory cortex, really involve a lot of integrated information, including autonomic information and that actually begins very early on and then proceeds up into insular cortex, so this revision sort of has validated some of the ideas of pain being much more than just this exteroceptive pain pathway. And this also is supported in animal models as well, so when you lesion insular cortex in rats, it reduces the allodynia that is seen after a mononeuropathy, so we have a biological correlate besides just what I’ve described using imaging, and next. And also, in human data as well. So imaging is useful in giving us a nice correlate but when you actually have some type of lesion study, that is really been sort of the mainstay of neurology and we see actually with injury to that area of cortex that there is a central pain and sensory loss that can occur as well. So that takes us to about 2007, where a new modality really came to the forefront and this was really discovered by placing patients or healthy subjects in an MRI scanner and letting them just sit at rest for seven or eight minutes and just capture the bold signal over time and when that was really discovered, and so, what was discovered in that process was there were certain patterns that were consistent over time in patients and then between patients, and from that, developed the idea that there are certain networks in the brain that are active over time and that these are areas of co-activation were known as functionally connected and it has also been supported by them looking at white matter tracts between these areas, so there is some type of biological correlate to this physiologic response that has been seen. So is anyone familiar with resting state fMRI? I saw, yes. I figured you would be. So this is actually has really been one neutral that’s come to the forefront and what’s really nice about this is we don’t have to induce pain, for one, but then also, allows us to, in a very structured way, allow patients to just lie in a scanner and then just look at that activation over time and may offer more consistency. Next slide. So when this has been done, what’s been discovered is that there are certain resting state networks in the brain that seem to hold across patients and across time and these are a few of the networks and I’m introducing them here because we’ll be talking about them as we progress, but the default mode network, the executive attention network, the dorsal attention network, the salience network, and there are others. I think there are about 11 or 12 networks. Visual, processing, some that aren’t so relevant for the discussion today, but the ones that I’m listing here, I think are the most clinically relevant and useful. So the first one I just want to mention to introduce them is the default mode network and this is the area when you’re sitting, maybe some of you in this moment are sort of daydreaming about what you’re going to do at three o’clock this afternoon, or what was going on at home before you got on the plane or drove here. What’s being activated during that process is the default mode network and this is sort of just the typical pattern of activation of the resting brain, and I highlight down here on this image areas that have been correlated that also in this pain matrix, so we see funnel cortex, we see posterior aspects as well, and these are shown to be involved with episodic memory retrieval, autobiographical memory, and then, internal thought, so we see at least a few areas that are involved with memory. We also see some that are involved in the frontal areas, involved with social cognition, value based decision making, and emotional regulation. So a very relevant network to consider. So that’s the default mode network. The next one I wanna take a moment and talk about is the salience network, and we’ll be spending some time on this with our remaining time, and the salience network, So this is anchored in anterior cingulates or the front. They’re the ACC and the insula and amygdala as well, and again, highlighting some of the areas that were shown in this pain matrix. So here, this network has been implicated in integrating, filtering relevant autonomic and emotional information, and does draw in other areas, such as brainstem and amygdala as well, and then, the third, that I just want to mention is the central executive network. So this is prefrontal cortex and then, connections to posterior parietal as well. So this is the network that’s activated during cognitively demanding tasks and uses working memory, rule-based problem solving, and goal-directed decision making, but I think two key points here, One is these are areas that were seen in this pain matrix as well, so that’s one important point, and the other point is that this network is really dependent on information that’s obtained from the other networks, so the salience information that comes in is then fed, in a way, fed through connections to the central executive network for processing, making decisions, and using working memory. Next slide. So it’s been proposed that these networks work together and so we have down here at the bottom, we have the salience network, which is taking this information, mapping it to goals and information from the other networks to help drive behavior. That information goes up into default mode network, which is then activating for autobiographical memory, episodic memory retrieval, maybe associations with that information that has come up through the salience network, queuing that processing, and fitting that into sort of the story of your life, for instance, and then, also that information is fed to a central executive network for problem solving and decision making, and so, you can sort of see a model of chronic pain with activation of salience network and then its influence on executive function. You can see that in affecting memory or at least the associations with certain memories, maybe preferentially, and how these all function together to sorta model the human experience. And, that’s great. But what happens when it doesn’t, when some of the information that is persistent starts to, through neuroplasticity, starts to affect the system in ways that maybe aren’t as helpful, when looking at it from the perspective of someone who is trying to take in much more information than just the pain state? So what we have here is aberrant salience network dysfunction is associated with psychomotor poverty, reduced goal directed action. Actually, there’s a neuro degenerative state known as frontal temporal dementia, which probably seems to preferentially affect the salience network, so we can see that there are some correlates to that. Default mode network, in sort of a more aberrant state, can lead to excessive rumination and poor autobiographical memory, and I would guess that most people here are taking care of pain patients can sort of see this pattern, potentially, in some of the symptoms that are reported, and so default mode network has been implicated in meta-analytic studies with depression and default mode network is actually one of the networks that is thought to be implicated in Alzheimer’s Disease. So we’ve got the default mode network, potential dysfunction, and central executive network dysfunction, in terms of impoverished networking memory or sequential resource allocation, being able to make smart decisions about how to use your resources. So we can see, at least in some of these models, that in the disease state, we can start to see some correlates beyond this pain matrix actually starting to dissect out in a dimensional way, different complaints. So this has been looked at in chronic pain and as Chris had mentioned, he and I were on the clinical practice guideline development team for headache, and as a neurologist, those are the pain patients that we see the most, and when migraineurs have been studied using resting state connectivity, there’s increased connectivity between periaqueductal gray and right anterior insula, with frequency of migraine attacks so we know that there is some changes in terms of preferential information flow. Also, decreased connectivity with the amygdala and parahippocampus, which is involved with memory, and amygdala involved with a number of processes, so there are some correlations that we’re seeing in resting state connectivity in chronic pain. So I mentioned the salience network, and salience is how one interprets the importance of a physiologic state. I didn’t really describe that, ’cause I just wanted to introduce the networks as they are laid out. So this is how it’s interpreted and maybe part of the perpetuation of pain even in the absence of painful tissue injury as may have been initially experienced, so this network is also activated in viewing others in pain, so there’s a mirror neuron system. So your salience network may be activated when you’re in close proximity as someone’s describing their painful experience, or in personal rejection as well, and this likely contributes to placebo or nocebo effects. If there’s a perceptual bias, one direction or the other, that can occur over time, then that is going to have dramatic influence on how that information is processed, how that is fed forward into other networks, and how that drives the functioning of the brain. And involves a number of the same areas and has been shown correlation as I mentioned besides in chronic pain in a resting state, also with induced pain. And, so besides migraineurs, also in low back pain, we see this as well. Again, a lot of the same areas, but more, so temporal gyrus, neoprefrontal cortex, as I mentioned involved in central executive network. Precurseurs and posterior cingulate, which are part of default mode network, and anterior insula which is salience. So you can see the low back pain experience likely involves all of these networks, at least in a correlational way, and then, talking a little bit more about this salience and attention, so there seems to be some correlation beyond just painful experience to this perceptual bias that we notice in general. So aversive stimuli and bodily sensations, in general, may be perceived in a negative way, and certainly, I’m not sure about everyone here, but I’ve certainly been talking to fibromyalgia patients. I often hear about being exquisitely sensitive to noise, to smells, to certain scents, so there is a potential perceptual bias right there and an enhancement of this salience network. So what I wanted to outline here is that pain is this dynamic experience that can be represented spatial temporally, in a network that involves cognitive, affective, and sensorimotor activity, and the patients may not be aware of that, and they may be focused on the external environment, but the processing involves much more than just that external cue, and can lead to various subjective experiences, such as the fibro fog, that has been described for fibromyalgia and the efforts are still ongoing to map these dynamic relationships. There’s one other network I just want to mention and that is activation that seems to be correlated with reduced pain or reduced painful experience, and this has been described as the antinociceptive network, which involves a lot of brainstem structures and medial prefrontal cortex and this has been shown, when investing states that is in the chronic pain patient, at some point, the patient or individual’s mind may wander away from the painful experience itself, so focus on painful experience seems to involve a lot of salience network, but then, subsequent activation of other networks, or affects of function of other networks, but mind wandering away from pain is correlated with this activation of this network that’s involved with prefrontal cortex and brainstem. So here we have a potential target for activation and a lot of these pathways are serotonergic and noradrenergic, so those of you involved with pharmacological treatment probably recognize that some of the medications probably have some effects within this network themself, but there may be other ways to get at this network, and so, a potential putative target for intervention besides just pharmacotherapy. This also helps understand, potentially, how some types of attentional training, such as meditation may influence pain and may allow for cognitive behavior, May be part of how cognitive behavioral therapy is efficacious for some of the various dimensions. It also allows us to think about ways to target this network, stimulating the network through some neuromodulation or noninvasive neural stimulation. The beauty of these resting state images is that we can look at connectivity between a particular area of interest and other parts of cortex, so for instance, periaqueductal gray has significant functional connectivity with motor cortex, so it’s potentially feasible that stimulation of motor cortex actually produces activation deep within the brainstem, and certainly, our VA colleagues have looked at this motor cortex stimulation for treatment of pain with some success. So, that concludes my introduction of the topic, so the main takeaway points, I think, are that these models continue to evolve. Right now, they’re correlational There isn’t a lot demonstration of causation, but certainly correlation within these networks, and I think, intuitively, looking at these networks, in terms of their function, sort of helps to, one, get a greater perspective of the various dimensions of the painful experience, and then, two, actually offers a way, potentially, to at least provide some putative descriptions of correlates for patients to understand that their experience is actually mirrored when we look at chronic pain using, for instance, imaging modalities, and that these neural correlates are emerging in terms of understanding these comorbid disruptions of function-like attention and while still in its infancy and with many challenges, that this can advance pain treatment. So these were the objectives for the discussion today, specific versus convergent models of pain, these cognitive networks, and then my goal was to try to offer a bridge between the neurobiology as it’s evolving, and how that seems to fit well within this convergent model of pain. Thank you. (audience applauding) Yeah, I’m happy to entertain any questions you may have. Yes?
Okay, I want to thank you, Dr. Lewis. Fantastic presentation.
[Dr. Lewis] Okay, I think these work.
Fantastic presentation, and I think we do have a time for a couple of questions, if anybody has questions. I can start off with one as well.
[Dr. Lewis] You get to trump.
Yeah, I guess since I have the microphone, I can start my question.
[Dr. Lewis] Go ahead.
You mentioned a little bit about the serotonergic and noradrenergic as potential interventions. Other than pharmacological based, what do you see in your crystal ball as coming up in the future with what we’re doing with these networks and pain treatment?
Um, yes, thanks. So what I see is targeted neurostimulation, potentially. So there are some studies that show that stimulation of parietal cortex, which has a robust connections to hippocampus actually increases working memory. So there’s one way that this is already being demonstrated outside of the pain realm. There’s interest in looking at targeted connectivity between dorsal prefrontal cortex to affect network function involved with headache, and involved with depression, so at least in some dimensions, I think this is what I see coming, and we’re starting to see that in kind of a crude way still. That’s not meant for, if anybody’s doing this work. It’s not meant to be critical, but it’s sort of the first step in understanding stimulating different parts of the brain will maybe affect different aspects of pain. The next step, then, is to find, in a patient-specific brain, the area that is most likely to be effective, and that, I think is going to demonstrate a greater response. Overall, a greater effect size. So that’s one thing that I see. Mm-hmm. There are lots of challenges trying to correlate this with targeted receptor-based things, but that’s kinda beyond the talk here.
[Chris] Dr. Passamani.
[Dr. Passamani] Hi, this kinda actually goes with Chris’s question. So have you seen any studies or are people even looking at the involvement of fascial-type of physical modalities to help the pain and how that interacts with this mechanism, and if that also would make a difference, because there’s lots of challenges, obviously, with central brain stimulation, but I’m wondering if people are looking at indirect ways to create the same correction?
There are some studies that are looking at this. They’re still limited. There still are a lot of technical challenges that have yet to be overcome in terms of using this as a true biomarker for pain response. One is the way that the data is processed. One of it is having a large enough sample size, because the effect size is still, I think, in some conditions it’s smaller than in others, sort of depending on what you’re looking at, but there has been some work. I think the one that probably has, at least, that I’m most aware of specifically, in acupuncture, which is a little bit different, but there are some efforts to find those correlations, pre- and post-treatment, for instance, but that’s still pretty early. Yeah?
[Yusuf] Yusuf Syed of First Base. Just a quick question, kind of along the same lines, in terms of peripheral neurostimulation. You know, the trials are very early and spread PNS, but are you seeing any central remapping with peripheral neural stimulation that you’ve kinda come across?
Not that I have come across. I think that’s very ripe, but I think that’s still challenged. I think the interest in, I think there’s a couple things. One is if you find something that works, then we’ll just stay with it. Why do a lot of research of it to look at the central effects? I think that’s part of it. The second part is that it really requires looking at all of the really dimensions that we’re talking about here, so I haven’t seen a study where that’s been parcelated out. I’ve seen some attempts, but nothing definitive. I don’t know if that answers your question, but it’s ongoing.
[Captain Stephens] Hi, Captain Stephens of Corpus Christi. I know, anecdotally, when I see my patients that have a continuum of fibromyalgia, pelvic pain, sometimes low back pain, I always ask the question, “Were you abused when you were a child?” So many of them were. So is there a physical change or a trigger or something that happens that maybe remaps this pain thing? And how can we use that?
Yeah, I think that’s a common experience among providers and I think it’s certainly been recognized as a risk factor in a number of painful states. We even see it in chronic symptoms of concussion, that history of abuse or really, of any behavioral diagnosis prior to injury. So I think that there is a recognition of that and an appreciation of that in terms of the epidemiologic studies. How that influences this, I don’t think has been clearly described, but I think that would be a very important and relevant study to look at. How much time do I have?
[Chris] Oh, you’re good.
Okay, so this is, So I’m gonna go on a tangent a little bit here. So the National Institute of Mental Health has been working on something called the Research Domain Criteria for several years now, which is the idea of taking the mental, The focus there is on mental health, but that really applies in pain as well. It’s to take the symptoms and develop a model, a cognitive model that can be then used to develop new treatments. So for instance, when the studies in adolescents with anxiety, when they show faces, a spectrum of faces from very happy to very angry, a sequence of 10, and then you put kids without a history of anxiety in the scanner, they’ll select, I’ll say, the midpoint that’s neutral, is maybe, and I’m just making up these numbers, ’cause I don’t remember them exactly. Let’s maybe say the midpoint is five. You take anxious patients. They will be shifted perceptually, over two or three, so that what we, someone without anxiety would interpret as mildly positive, they will interpret as neutral. So this perceptual bias is now being looked at in terms of a target for anxiety disorders, and my gestalt, although I haven’t seen anything that shows this yet, is that that same bias probably influences response to pain and my guess is that’s probably very early on in the developmental process. Probably the earlier in the developmental process, that that aversive stimuli occurs, probably the greater the degree of risk for subsequent comorbidities along with pain. That’s just me talking, so I’m glad there was a disclaimer slide early on, but I think while that hasn’t been borne out yet, I think that’s the approach to take to answer your question, and I haven’t seen that study yet, at least in terms of correlations with what I’ve been describing. I think it’s certainly been described in terms of epidemiology, but not in terms of neurophysiology.
Any other questions? Okay, with that.
Thank you.
Colonel Lewis, thank you again very much. (audience applauding)