Hi there, and good afternoon. My name is Jennifer Squibbs. I'm a member of the Professional Development Committee, and welcome you to the afternoon session. Before we begin, I have a few announcements. Just a reminder to use the AANA meetings app where you will claim your CE credit by performing the evaluation for this session. The evaluation will open 15 minutes to the end of the session, and as a reminder, you have until Monday, September 9th at noon Pacific time to submit all of your evaluations for the Congress sessions to claim your CE credit. Lastly, mark your calendars. Remember that we will be seeing you again in Nashville, Tennessee for the 2025 Annual Congress. If you'd like to speak or share your expertise, abstract submission will open on August 14th. The instructions and template for submitting an abstract is available on our website as long as a learning module on how to do so. Now it's my pleasure to introduce our speakers to you. Dr. Lori Shirley is an Assistant Professor of Research at Vanderbilt University School of Nursing. Ms. Noquiti is a PhD student at Vanderbilt University School of Nursing and a practicing CRNA in Charlotte, North Carolina. Please join me in welcoming our speakers as they present, That Blood Pressure Cuff Really Hurts, What Every CRNA Should Know About Pain Sensitivity. »» Hello everyone. Thank you for being here. My name is Nanye Noquiti. I am a CRNA and I'm a PhD student at Vanderbilt University. Here with me today is my mentor, Dr. Lori Shirley. And today together we will be presenting Pain Sensitivity, What Every CRNA Should Know. So before we start, I'm going to say that we do not have any conflicts of interest to disclose. And our learner objectives today will basically be at the end of this talk, everybody should be able to describe what pain sensitivity is and how we measure it and why it is important for us to assess pain sensitivity. So that blood pressure cuff really hurts. I'm sure we have all heard it from our patients. Subconsciously we begin to think of the patient's handling of pain and actually the surgical pain that they're about to experience. And we are thinking about pain sensitivity. But we may not know that's what we're thinking about. So the question is, why is it important for CRNAs to understand pain sensitivity? We do because it affects our daily practice, whether we know it or not. Our ultimate goal is to be able to improve patient outcomes. And someday maybe it will be part of anesthesia pre-op evaluation. So pain sensitivity is a concept that has not been fully understood, yet research on its use in the treatment and management of pain is becoming increasingly popular. Until recently, there had never been true definition of pain sensitivity. The International Association for the Study of Pain defines pain sensitivity as the characteristic of an individual which determines how the individual receives pain stimulus. In our today's talk, our aim is to show how pain sensitivity can be measured in an objective way and standardized way as well. Our current lab work focuses on the way it impacts post-operative outcomes so that we can ultimately use it to tailor pain management to an individual's specific needs. And at the end of this talk, you will find out that being more pain sensitive does not really mean giving more opioids. So pain sensitivity is a person's level of responsiveness to pain. It is very highly variable among people. You can give the same stimulus and then get different responses. It is influenced by genetics, which contributes to about 50% of the variability that we see in pain sensitivity. Previous pain experiences, psychological factors like anxiety, depression, environment, peripheral and central sensitization, which we will talk about. Nociceptors, what are they? These are efferent nerve fibers that transmit painful stimulus from the peripheral tissue to the dorsal horn of the spinal cord. And this is pain pathway. So there are two peripheral nerve fibers that are responsible for the transmission of pain stimulus. They are small myelinated A-delta fibers. They're responsible for localized fast pain. So it makes you to react quickly. That withdrawal helps you to avoid further injury. And then we have the myelinated C-fibers. They're responsible for diffused slow pain. The intensity of pain increases with time and it causes you to guard. So this is a picture of the actual electron microscope of the free nerve fibers. So let's talk about peripheral sensitization. This is when normal nociceptors maintain high threshold of activation. So they don't just start to, they don't have spontaneous activity. But when you have peripheral sensitization, you have low threshold for activation of peripheral nociceptors. So that's increased excitability and amplified response to nociceptors. So these are the channels that help to, actually normally these channels are not, they have high threshold to be excited. But when you have peripheral sensitization, they're very well excited fast. So central sensitization. This is caused by reduction in firing threshold of spinal nociceptors. Increase in discharge of spinal nociceptors. And then amplified pain from peripheral nociceptors. So we have two subtypes. The bottom up. This is caused by constant nociceptic input from the peripheral nociceptors. And then the top down, which originates from the supraspinal structures from the brain. This shows the different responses that we have to stimulate. First we have the threshold. We have the sensation threshold, which is the point at which an individual first senses a stimulus. And then we have the pain threshold, the point at which that stimulus first becomes painful. And then pain tolerance. The maximum painful stimulus an individual can tolerate. And then the responses to the stimulus, we have hyperesthesia. This is where a stimulus is felt at subthreshold. You can see over there, I don't have a pointer, I would have shown you right there, before the sensation threshold, the person who has hyperesthesia, they start to feel the stimulus. And then we have the hyperesthesia. The stimulus is felt at higher threshold. Aledonia. At that point, that stimulus is not supposed to be painful. But that person feels it as being painful. Such as light touch. Light touch shouldn't be painful. And then we have hyperalgesia. Increase in pain sensitivity and exaggerated response. And then the hyperalgesia. These are people who it takes like incredible amount of stimulus to make them feel pain. Why do we assess pain sensitivity? First it helps us to diagnose pain accurately. It helps in targeted individualized pain management. Early identification and management of high pain sensitive patients decrease sensitization, which can eventually lead to chronic pain. It also improves outcomes and satisfaction. So how do we assess pain sensitivity? We do that using pain sensitivity questionnaire. And then quantitative sensory testing, which I'm sure most of you have not heard. And that's our focus for today. So it measures complete somatosensory phenotype of an individual. So QST. This was founded in 2002. It is one of the most validated QST protocols. The one I'm talking about is the German research network on neuropathic pain. So it was founded in 2002 and one of the most validated QST protocols. It gives complete somatosensory profile characterization. It has about seven tests that measures 13 parameters. So we use that to assess pain sensitivity. It assesses neurofiber function or dysfunction. It uses standardized stimulus, hot, cold pressure, pain break. It measures, it mimics natural or mechanical thermal pain sources. And I'll say that it is the most validated. QST can be grouped into those that measure pressure, mechanical, vibratory, electrical, and thermal. And we have two kinds of that. We have the static QST, which assesses the peripheral nerve function. Examples are cold, hot threshold, pain pressure threshold, and vibration threshold. And then we have the dynamic, which determines central sensitization. And then the two key tests from that that we will discuss today is temporal summation and condition pain modulation. It is not really feasible to run all the 13 QST parameters in the clinic area. And there is no consensus on which QST parameters are most predictive of particular pain states. We have visceral pain, just like the patient that has had hysterectomy. And then we have the musculoskeletal pain. So the visceral pain is different for most people from the musculoskeletal pain. And we have different QST parameters that can determine those. So a few of the most used QST parameters that we will talk about today is PPT, pressure pain threshold, thermal testing. We have cold, warm detection threshold. And then we have hot, cold pain threshold. And then we have the temporal summation and the condition pain modulation. So right here, I'm going to let Dr. Shirley come and tell you guys about this test, because this is what she does very well in her lab. And I am a student in her lab. So Dr. Shirley, over to you. »» Great job, Nanye. So I'm going to go over some of these tests. This is a poster that two of the neuroscience, we have two neuroscience undergraduates that are working in our lab. And they put this together for participant education. So I'm going to go over each of these tests individually just to give you an idea. Because in a few minutes, I'm going to talk about some of the research that has gone on. And it's really escalated in the last two years about quantitative sensory testing and how it relates to participant or patient outcomes. So this is in the picture on the gurney, I guess, or bed is Anna. Anna was coming over to train in QST in my lab at the time. And she is wearing a thermode on her leg. And in her hand is a patient response button. And then Nanye is running the computer, which is running the thermode, the different temperatures that Anna is feeling. And then we've got observers. So the first one I want to talk about is thermal testing. We do three tests. And as Nanye said, we do a complete German research network protocol for our QST. And that's unusual. Because when I talk about the research in a few minutes, you'll see that most studies that have looked at the association between QST and postoperative pain or postoperative opioid use have only picked one or two. And it doesn't appear to be an evidence-based way that they pick the two. It's probably related to the easiest ones to do in a clinical arena, which makes sense. Because if you can't feasibly do it in a clinical arena, it's not going to be an effective measure. So that's one of the things that we are working on is to find the most feasible, the most predictive and the most feasible tests that can be implemented in a clinical arena. So we have decided in our lab to do all of the German research network protocols. And this is a protocol that was started in 2002 by a group of German neurologists who were studying neuropathic pain. And although they were studying neuropathic pain, it turned out that the protocol that they developed was very predictive of chronic pain. And it's been used a lot in especially chronic overlapping pain conditions. So it has been adapted by the pain research community. And so we are doing it in our lab. It takes about 30 minutes per site to do. And we do two sites. So we do the arm for the control site. And then our population is a total knee replacement population. So we do the operative leg as their surgical site. And so that's an hour of QST. There's no way that we're going to be able to implement that clinically, nor should we. Our goal is when this study is finished and then when we move on to Nanye's study is to figure out how we can shorten that and make it meaningful and make it clinically applicable. So right now, I'm telling you about a lot of tests that we do in the lab. But again, we are doing everything right now. The participants are coming away with a complete somatosensory profile. And we're hoping that we will, however, when we do the analysis, we will be able to narrow this down to two or three tests. So we do thermal testing, three types of thermal testing. We do a warm-cold detection threshold. We do a thermal sensory alignment. And we do a heat-cold pain threshold. And I'm only going to talk about the heat-cold pain threshold as an example of what we would do for the thermal testing. But we have a thermo that we attach to a participant's leg. And we deliver, so the baseline temperature on that is 32 degrees Celsius. And then we increase or decrease. If we're doing cold pain detection, we would decrease the temperature one degree Celsius every second. If we're doing heat pain detection, we would increase the temperature one degree Celsius every second. And then we give the patient a response button. And they would push the button when that sensation feels painful to them. So on the screen at the bottom, you see this is what the computer screen would look like. So in this particular participant, for the cold pain detection, they detected pain at 28.5 degrees Celsius, 28.1 degrees Celsius, and 28.4 degrees Celsius. So we average that number across the three. So when we put this thermo on, for instance, for heat, as it is first put on, and there's a few of you in the audience who have done this, have been guinea pigs in the lab for this. At first, it feels room temperature. And then it starts to feel warm. And for me, I was thinking, oh, it kind of feels like a heating pad. I like heating pads. This is nice. And as we continue to ramp up the temperature, there comes a point where all of a sudden it becomes stinging or burning, and it becomes uncomfortable. And that is your heat pain threshold. And that's the number that we're after. It varies across the population. So this is the thing that we're testing. So that's just an example for the thermal. We also do for touch, and then I should say for the heat pain, that is the point where your C-fiber fires. For the cold pain, that's the point where your A-delta fiber fires. So that's really what we're getting at. For pressure, for touch, we use pressure. And there is a set, Kenyatta, you're up. So we have a set of, we use Von Fray filaments for this, and it doesn't show up very well in this picture. But on the top picture, you see one of the people training in the lab, Madonna's holding the device. We touch it to the participant's skin with their eyes closed, and we ask them, do they feel us touching them or not? And we start with filaments that are about the size of a human hair, and we move up until we get to a point where we find one that they can consistently feel. So Kenyatta's been kind enough to move these around, or kind of send these around the room so you can take a look and see what we're looking at. But this is checking A-beta fiber firing and function. And if this is painful, this is an indication of aledinia. So this would be one of the tests that would classify them for aledinia. We also do pinprick detection to see if the participant can detect between sharp and dull sensations with a paper clip and a safety pin. The next test that we do is temporal summation. This test uses a weighted pinprick. So you can see in the picture, that's Madonna's hand again. And we are holding, what we're holding is a hollow tube, and inside of that is a weight with a pin at the end. So you can kind of see how her skin is depressed. That is depicting the weight, the pressure, this is a pressure test, the pressure that that weighted pin is exerting on her skin. Most people do not feel this as pain, or they feel it, we use a pain scale for this that goes from 0 to 100 millimeters. And most people will rate it as a 0, somewhere between a 0 and 10. So on a 1 to 10 scale, it would be 0 or 1. Anything above a 2, that would be considered hyperalgesia. And so we do one stimuli, we have them rate the pain, and then we do 10 stimuli. At the end of 10 stimuli, we have them rate the pain a second time. And the difference between the 10 stimuli and the 1 stimuli is called temporal summation. And this is testing for wind up. This is the QST that tests for central sensitization, because if the person, if giving the exact same stimuli 10 times elicits a much higher response, then that means that your central nervous system has ramped up the transmission, transduction, and perception of that pain. And so we have seen, I have had, we've finished baseline data on about 50 patients so far, and I've seen three people where I've had to stop the test. Now most people don't feel this as painful, remember. I would say 85% of the people don't feel any pain at all from this. So actually, it gets to the point where it's unbearable, is a pretty good indication. And these are people who are going in for knee replacements. These are participants, these are patients that you're seeing in your operating room. And so it looks like from our data, maybe, well, I don't want to give you, we're not done collecting data yet, but there are a significant number of people who are demonstrating central sensitization. And this particular test is testing A delta and C fiber function. So the next one is pressure pain threshold, and Kenyatta also has an algometer. So we test pressure with an algometer. That's a device, as you can see here. This is a computerized one. We have a non-computerized one, a manual one going around the room. And we put the electrode, we put the foot of this device on the patient's skin. And it would be, again, we test on the arm and the operative leg. And then we push, giving a standardized, for our particular one, we measure it in kilopascals. So it would be 30 kilopascals per second. And we increase that pressure until the point where the patient's participant says that it's painful. This particular test, as you can see with the picture up at the top, you have free nerve endings at the surface of the skin. And so our touch and our pinprick and our thermodes are all testing those free nerve endings. But you also have free nociceptors deeper in the tissues. And so we're using an algometer to get at those deeper tissues. Again, a lot of people believe that this is a test to use for orthopedic populations. I'm not convinced, and maybe you won't be either when you see the data that we've dug into about this. But again, that's hitting A delta fibers, that's hitting C fibers. And we can, there are age and sex match standards that we compare our participants' data to so we can tell if they're falling into the allodynia or hyperesthesia or hypoesthesia categories. And again, hyperalgesia. So the last one I'm going to talk about, we don't do this one in the lab, is condition pain modulation. But a lot of studies do look at condition pain modulation. It is the second QST that tests for central sensitization. It's actually a test of your endogenous opioid system. So in this particular test, you have two pain stimuli. In this first picture here, they're applying PPT or pressure pain threshold, which we talked about where we put the algometer against the skin and press. And if that's going around, when you get that, press down and see how hard you have to press to get to a painful stimuli. It's quite a bit of pressure. So we do that first and mark the pressure at which the participant says they have pain. And then we put a second pain stimuli or a modulating stimuli on the body. Usually it's either a blood pressure cuff. In this case, it's a blood pressure cuff. It could be putting your hand in an ice-cold bucket of water. And then you blow the blood pressure cuff up until it gets to a painful stimuli. You leave that inflated at the painful level. And then you apply that first stimuli that you did in the same location. And that pain sensation should be lower than it was without the conditioning pain. And that's a function of your endogenous opioid system functioning. It's an assessment. And it also kind of demonstrates gait theory of pain. So we've referenced central sensitization a few times, or centralized pain, also called nosoplastic pain, a few times in this talk. And I just want to take a minute to talk about central sensitization. I mean, I give an entire talk about this. So this is going to be a pretty rapid overview. But one of the pain types that we're looking for with QST is centralized pain. It is pain that is augmented through the central pain pathway, including the spinal cord and the brain. Chronic pain types are mostly thought to be mixed pain types. But most of them do have, unless it's purely neuropathic pain, most of them do have a component of central sensitization. So along the bottom of this continuum, there is a group of chronic overlapping pain conditions that and where they kind of fall in the centralized pain continuum, with fibromyalgia being the prototype of that, almost purely centralized pain. There's really no peripheral input that has ever been identified, for the most part, for causing fibromyalgia. And as you move down that continuum towards nociceptive pain, you can see that there's different degrees of central sensitization typically seen with those conditions. So we typically see people who have osteoarthritis. So they're on the low end, but they do have some degree, usually, of central sensitization. So why do we care about central sensitization? Because it doesn't respond to our therapies the way that typical nociceptive pain does. And in particular, it doesn't respond well to opioids, and it doesn't respond well to NSAIDs. Now, surgery or injections, if it's a purely centralized pain, in fact, putting anything in the body that's going to stimulate some kind of peripheral sensitization is going to augment the pain and make them worse. So this is why it's critical to find these people ahead of time, because replacing their knee may not be the best plan until you've at least treated a component of their centralized pain. Some things that have found to work pretty well with centralized pain are SNRIs in particular, agonists, cannabinoids, and MDA antagonists. Tramadol does have a lot of other properties other than just being a weak opioid. And then the non-pharm, there's pretty strong evidence that things like, in particular, transcranial, oh, I always forget the name of that, but transcranial stimulation or things that act subcortical in the supraspinal. And then the other one that's worked pretty well is VR. And there's a collaborator of mine out of the University of Maryland who uses VR headsets for TMJ, which has a high degree of central sensitization. And she's getting pretty good results for that. So this is why we care. And this is why it would be a really nice thing to pick out these people who have a high degree of central sensitization before we have them go in for surgery. So I'm going to pivot and just talk about some of the studies that have looked at the association between QST and post-op outcomes, especially chronic pain or persistent pain after surgery and chronic opioid use. So when I first wrote the grant for the study that we're conducting now, it was in 2001. And there were only a handful of studies that looked at this. I think I cited five studies in my grant. We started this work in 2022. And look at how many studies. I mean, it has just escalated. 23, same thing. And in 24, Nanya and I kind of ended this particular lit review in March. So there's only a handful of studies. But I am sure that it's going to continue to climb. This is a very hot area of research. And the people that are looking at this most are the orthopedic surgeons, because they're the people that are dealing with the post-operative chronic persistent pain after surgery and the chronic opioid use. So we dug down into this. And I'm going to see if you can see this. Yeah, you should be able to see this. We dug down into this literature and did a deep dive. And to orient you to this table, across the top are some of the quantitative sensory tests that we've been talking about. So you'll see cold detection thresholds. The second line, CDT is cold detection threshold. WDT is warm detection threshold. CPT is cold pain threshold. HPT is heat pain threshold. And then move down a little bit, and you'll see up on the top line where it says study, TS is temporal summation. PPT is pressure pain threshold. And then CPM is condition pain modulation. So just to orient you, you have some reference for what some of these tests are. And then, of course, along the left-hand side are the studies. And I first looked at the first studies that started coming out about this were spine studies, spine surgery. So I kind of looked at a handful of those. And if it's a green Y, they found a significant association between QST and postoperative pain. If it's a red N, they did not find an association, a significant association. So you can see, in the spine population, the data was pretty good. I mean, I haven't dug down. I'm not presenting you the effect sizes. So I'm not really telling you whether it was clinically effective. But the data was pretty good that we're onto something here, and QST could predict postoperative pain. But when you get down to the total joint populations, which is the study that we're doing right now, it's a mixed bag. Some studies have found, and if it's a small C, that means they found the significance at the control site. If it's a small S, they found the significance or didn't find it at the surgical site. So when I first put this together, I thought, well, you certainly can't conclude anything from that. This is pretty inconclusive. But where the tests did, or where the study did find significant findings, they were testing the surgical site by and large. So that was the first takeaway. So note to Nanye, you might want to be checking the surgical site, not the control site. The other thing that was a big eye-opener for this was nobody is doing the thermal tests. They're all doing either PPT. PPT is definitely the most common. Then they're doing temporal summation, and they're doing condition pain modulation. So it's really hard to tell whether QST is going to be predictive of postoperative pain if people aren't testing that particular measure. So we have, and we aren't the only ones that found this. There have been several systematic reviews. The first one that I have on the screen here is Sangla Sand. He published this one in 2017. The majority of those studies were looking at postoperative pain while patients were in the hospital. So either PACU, 24 or 48 hours. And this is related to a time back when patients would stay in the hospital for three days after a total knee replacement. So not really relevant to how our practice is today. The next three are more recent systematic reviews, and all of them have concluded that they really can't make a conclusion because there's too much variability in what test the study does, how they analyze the data, and at what time point they administer the QST, and at what time point they're measuring the pain or opioid use. So we're kind of in the same boat here. QST looks like it's going to be a very helpful measure that we could use to predict people who aren't going to do well after surgery, but the science isn't quite there yet. In fact, there was a 2020, one of the editors of the Arthroscopy Journal said this is something that we need to keep on the radar. And he went as far as to say we should probably be testing every patient for QST before they go in for surgery. Now, I believe that we are probably going to start measuring a certain subpopulation. I think that the science isn't there yet about who those people should be. And the other question that's unsettled is, will we be doing it in the orthopedic surgeon's office, or will we be doing it in conjunction with the anesthesia pre-op? So I'm going to tell you a little bit about our study. This is an NIH study where we see people at three time points. These are people who are going in for total knee replacement. We see them preoperatively at time one, and we collect some demographic and health history data. We collect data, survey data on depression, anxiety, some information about their pain. And then we give them the central sensitization inventory, which is a survey that picks up on central sensitization. And then we put them through the entire German Research Network protocol in two sites, again, the arm and the leg. And then we also get, as a component of this, I'm very interested in the genetic markers of central sensitization and pain sensitivity. So we collect DNA from them. We're collecting it for both genetic markers and for gene expression. And we'll probably be analyzing that data, I think, around January. We'll have everybody through all three phases of this test. So then we have them come back at post-operative week two, and then we have them come back at post-operative week six, and we do the exact same protocol. And the objective is, our primary outcome is, is there a difference in opioid uses between people who are highly pain sensitive and those who are not, are low pain sensitive? And we've seen a variety across the, like I said, we've just enrolled our 50th participant. So we've had, seen a variety of pain sensitivity, which mirrors what the normal population is. And then our secondary outcome is their chronic pain, or how much pain they're in. We don't follow them past six weeks, but how much pain they are in at six weeks. So these are very, very preliminary results. This is only, this is representing 40 participants' baseline data. Only 33 of them we have the outcome data for. So on the, on the left-hand side is the particular test that we've been talking about. So cold detection threshold, warm detection threshold, and I'm only presenting heat pain threshold here. And then below that red line is the temporal summation data and the pressure pain threshold data. And then across the top is the total population. So that's men and women together, so the full 33 participants. And then we've broken it down by sex. And we were quite surprised by these findings. Now, you'll see none of these are significant because we are powered for 60 participants. And we're only presenting you with half. We only have outcome data on this on half. So typically what happens when you do an interim analysis like that is the trends that you see in the data will get stronger and you'll get significance once you get all the participants in. So this is really early peek at the data. And what I'm presenting to you here is a Spearman's row, which is a measure of correlation. Think of it like your Pearsons are, but this is the measure of correlation when your data is ordinal. And so anything from a 0.4 to like a 0.6, 0.7 is considered a moderate association. And we have some interesting findings here. And the first thing I want to call your attention to is if we only looked at the total sample, we would have null results because really those are either no correlation or very low correlation. And again, don't look at the P's because none of this is going to be significant yet. But when you look at the difference between males and females, it's striking. And it did not go in the direction that I thought it would. QST is more associated or more correlated with postoperative pain. And this is at two weeks. Postoperative pain at two weeks in males than it is in females. And this is very counterintuitive because females have higher pain sensitivity. They're more pain sensitive than males. And they have a higher incidence of chronic pain than males. So the fact that QST is more, at least in this early look, is more correlated with postoperative pain at two weeks was a surprising finding. And nobody is looking at this sex stratified. So it's a surprising finding that I think our pain colleagues are going to be pretty interested in. The other thing that I would call your attention to is if you look at which tests are most correlated, it is not the ones that are most commonly used. So the PPT and the temporal summation, and again, we don't do CPM. But those are not the ones that the bulk of this data is telling us are most correlated. It's the thermal ones. And the reason that that data picture may be mixed when we look at the studies is because we're not looking at the right tests. So this is another more of where Nanye's work is going. So I hope after this talk, you have a better idea about what pain sensitivity is. We deal with it every day in our practice. And while we haven't yet harnessed it as a measure we can use clinically to help us in our practice, more and more research is helping us move in that direction. So we need to empirically determine which tests are most predictive of postoperative pain. And then we need to develop feasible and affordable ways to implement it into clinical practice. Preoperatively, we measure blood pressure, heart rate, respiratory rate, lab values, EKG, and other tests. But we have not found a way to measure one of the most major components of anesthesia, and that's pain. Whether we see these tests implemented in orthoclinics or in anesthesia pre-ops, I believe pain sensitivity will become a component of our pre-op standards. And Nanye's planned research will build upon this prior work, including my own, and move us toward that goal. So I'm going to have her come up and talk a little bit about what her dissertation plans are building off of this data. All right. I'm going to finish up by telling you guys what my research focus is. So I'm doing a preoperative use of quantitative sensory testing to predict postoperative opioid need in patients undergoing total knee arthroplasty. As I stated earlier, non-preoperative tests are not the only way to measure pain in total knee arthroplasty. As I stated earlier, not all QST parameters can be predictive of musculoskeletal pain, and it is not feasible to run all the 13 QST parameters in the clinic area. The goal is to develop for clinical use only the QST parameters that are highly predictive of postoperative pain and opioid use. So I am currently focused on the TKA population because research has indicated that this is a surgical population that is highly variable in their postoperative pain and opioid requirement after surgery. The focus is to determine if QST and which QST parameters can accurately predict postoperative pain and opioid need of TKA patients. This will help in individualizing surgical pain management after TKA. So the first thing I'm going to do is to analyze Dr. Shirley's existing data of patients undergoing TKA, and then to find which QST parameters were most predictive of pain and opioid need for those patients after six weeks. Then I will then implement these predictive QST parameters in the clinic area to assess pain sensitivity on those patients undergoing TKA, and then to determine if actually the QST parameters can accurately predict their postoperative pain and opioid need six weeks after surgery. And also to even determine if these are feasible to run in the clinic area because we can have all these tests, but what is the use of it if we cannot use it in the clinic area because it's not feasible? So the goal is to develop a physical QST protocol that can help to guide postoperative pain management, and this can give way to further research on individualized pain management and help in identifying those patients who may be at high risk for persistent postoperative pain and precisely and aggressively manage them to avoid them transitioning to chronic pain. And that's it for us today. Thank you all for staying. Appreciate that. If you have any questions, we can entertain those. I'd also like to acknowledge the people in the lab that have made this research possible. Like I said, we have two neuroscience students. This is exciting. Not too many CRNAs have their own research lab. And we have this lab at Vanderbilt University. We have two neuroscience undergraduate students who are pursuing, one is pursuing a degree in medicine, one is pursuing a degree in nursing. We have an individual who has a master's in pharmacology and is taking a gap year to gain research experience before she goes to med school. We have a research assistant in a chronic pain clinic who does alternative therapies, acupuncture, yoga, tai chi, cognitive behavioral therapy. And they're instituting QST as a clinical component of their practice. So she has come and she's training in the lab. And then we have Nanye, we have another CRNA PhD student starting next month, or actually this month, in two weeks. And we have other people who are interested. So our lab is a lab that is interested in training CRNAs who are serious about research. We'd love to, if you're interested in research and you have any questions about what path to attain, or you want to come and talk to me about possibly learning in my lab and in our environment, I would love to speak with anybody here. But I do want to acknowledge the people that have made this research possible and are continuing to make this possible. So I always like to put that acknowledgment aside. Excellent talk. Are you teasing out the variables of patients who have prior knee surgery, prior to their total knee arthroplasty? Yeah, for this test, because this is a career development award, it's a K award, so you're relatively limited on your funding for that. A K mostly funds the PI's salary while they're building a lab and building your staff. So there's not a lot of external funds. So we only have 60 as a sample size. But we've mirrored, almost to the letter, the protocol of my mentor, Susan Dorsey at University of Maryland. She has a study where she did chronic pain. So to answer your question directly, we have excluded chronic pain patients and people who have had previous knee replacements or previous surgery on that knee. But we're planning on compiling our results together. So I think she's got 200 chronic back pain patients, and she's got about 150 leg fracture patients. And so we're going to pool our data. And she also has RNA data. So she's looking at gene expression, too. So we'll have over 300 patients. So we'll have a lot more data. And they did not exclude chronic pain patients. So although the question about previous knee surgery, we haven't got to that yet, I think that the answer to how chronic pain impacts this will help tease out that. Thank you for your question, Trish. Hi, there. Julia Harris from California. I have two questions with second question part A and B. So first question is, have you considered or are you testing for catastrophizing scale in these patients? Yes. And I'll tell you, I hate the title of that scale. But that is one of the patient reported outcome scales that we're collecting, because that data is pretty high. It's pretty highly correlated with pain in all of its forms, especially chronic pain and centralized pain. So we are collecting that data. I heard a talk not too long ago by Dan Claw, who's kind of a guru in centralized pain, that he said that a lot of the things that we talk about do tend to have gender overtones that are, I don't know, I can't think of the word right now. But probably what we're calling pain catastrophizing is probably PTSD from previous pain experiences not being appreciated, believed, understood. So I'd like to think a bit more about that than pain catastrophizing. But we are absolutely collecting that and including it as a variable. My second part of the question is, you had indicated that you foresee being integrated into clinical practice, but on a subset of population. Do you have a general idea of what population that would be? And then the second part to that was to touch on your kind of indicator that it would need to be clinically feasible. Do you have any concept of what that would look like? So to answer your first question, I don't know yet. That's Nanya's going to answer that question for us when she analyzes the data. But I suspect males, although females tend to have higher pain sensitivity as a rule and overall, and although females tend to have higher incidences of chronic pain, males have higher incidences of postoperative persistent opioid use. And the fact that our data showed that QST was more correlated with prolonged pain in males is something that we would definitely need to dig deeper into. Because I'm not saying that we should reserve it to males, but there's something there. There's some signal there that I'm interested in pursuing further. We do get the central sensitization inventory. That would be a very, it's a 25-question survey that participants take about five minutes to take. That would be one that we could implement in the clinical setting, and if people score higher on that, that may be the people that you test. There's also, as Nanya kind of indicated, there's a pain sensitivity questionnaire that just came out. It's really less than five years old. I've only seen a handful of studies. So far, it's not super correlated with QST, but most of the studies that are looking at QST are only looking at PPT and condition pain modulation and temporal summation. So maybe it is correlated more with the thermal QST test. So that's something that's on my radar, too. So not sure yet, but I think we'll know within the next year, right, Nanya? Thank you so much. Good afternoon. Mickey Ballester from South Carolina. My question is about the DNA that you're pulling. It's a little two-part. What are you looking at and why? And then did that influence your IRB and security of your data and all of that? Oh, it always does. You have to have a separate consent. If you're doing anything with genetic data, you have to have a separate consent just for the DNA. And the individuals have to consent whether they allow you to do DNA analysis with the data and with the specimen. We're only collecting it for DNA. So if they don't sign that part of it, if they don't check that box, then we don't even collect it. And I've only had one participant out of 50. And I'll say, we've had very little dropout. As burdensome as you can imagine it would be going through an hour's worth of pain sensitivity testing, the patients are so engaged and interested in this that that's been a surprise to me. And then they have to sign another. They have to check another box to say that you would allow it to be used in follow-up research for this particular study. So I will tell you, I only have the money to look at gene expression in this first round because that's going to cost about $35,000 to do. We have 180 specimens because we have 60 participants and we see them three times. So to do gene expression on 180 participants is going to be about $35,000. We've banked two vials of blood for each participant because I very much want to, in this study, find money to do epigenetics, especially DNA methylation with this data. And then we've saved another test for anything that may happen in the future. So they have to check three boxes. And it's all de-identified. It's only tagged with a number. There's a separate linking list that you keep with the participant's name and what the number is on the vial. And when the vial goes to the lab, we have it in a minus 80 freezer that's in a different building from where that linking list is. And then when that vial goes to the, we're lucky that we have a DNA, a very robust DNA department or genomics department at Vanderbilt. So they tag each of those specimens with a barcode. And so you don't, there's no way to trace back. And we do not do, the only thing that we're looking at gene expression is about 20 pain genes. OPRM1, if you're in the pain genetic space, OPRM1 is the gene that codes for the immuno-opioid receptor. It's the most studied. Early on, there wasn't really a lot of data that came out that said that it was predictive of pain or opioid use. I'm seeing some new data come out that maybe it is. So OPRM1, COMT, the COMT gene, and then probably about six or seven inflammatory markers. We're looking at that because those are the ones that are popping for correlation with people who develop centralized pain and develop postoperative persistent pain. So we haven't select, we don't have to select those genes until we run the data. So we're continuing, I've got this file with 200 studies in it, and we're collecting that data. And as I get closer, as I said, Susan Dorsey is my primary mentor on the genetics piece. And then I have Nancy Cox at Vanderbilt also, an internationally renowned geneticist who is going to help me select those genes when the time comes, which is several months away, but it's coming up quick. All right, well, thank you very much. Nanye, her very first talk at ANA, so she did a great job. Thank you.

Jennifer Squibbs

Professional Development Committee

AANA meetings app

Annual Congress 2025

pain sensitivity

Quantitative Sensory Testing

postoperative pain

gender difference

total knee arthroplasty