Dr. Alexander Chamessian shares an overview of treating patients with neuropathic pain and when they should be referred for pain management evaluation.
All right. And without further ado, our first presenter today is Doctor Alexander Tremesian, who received his medical degree and his PhD in pain neurobiology at Duke University School of Medicine in Durham, North Carolina. He then completed his residency in physical medicine and rehabilitation, as well as his fellowship in pain medicine at Washington University School of Medicine. Uh, he is currently an assistant professor of anesthesiology in the Department of Pain Management with the Washington Physicians and sees patients at Barnes Jewish West County Hospital in Creeve Core. Is that the only location you see patients at? That is, yes. OK, right. I just want to make sure it wasn't a typo on the website. He specializes in neuropathic pain, diabetic peripheral neuropathy, small fiber neuropathy. Chemotherapy induced peripheral neuropathy, idiopathic peripheral neuropathy, immune-related peripheral neuropathy, Jillian-Barre syndrome. There there's a theme there, Nicole, neuropathy. I'll go into that. No worries. It's a lot of neuropathy. And that's what we're gonna talk about today. All right, well, I will let you go ahead and get started then. I appreciate it. All right, thanks so much for that introduction, Nicole, and thank you everyone for your time uh and uh giving your lunch hour to hear about this important topic that you probably encountered quite a bit. So as Nicole said, I'm a uh a pain management physician and I'm also an investigator. Here at the WasU Pain Center. I'm actually downtown in my lab right now, which is where I spend most of my time, but once a week, I have a specialty clinic at Barnes West County, where I focus exclusively on, on patients with pain due to um a neuropathic condition, and we'll go into all that today. Um. So learning objectives, I'd like to discuss and identify neuropathic pain in uh patients. I wanna help, I wanna help equip all of you to to do this, to identify these folks, and to um also give you the the knowledge and tools to begin the management pathway, but then also uh to understand uh whether and when those patients should come to me. And to tell you what I can do for them. So first, let's have some shared language. What, what is pain? Um, we, the English language or really any human language doesn't have enough words to fully describe the kind of sensory experiences that we all have, but pain is a universal kind of construct and the official definition of it by the, uh, the Society for the Study of Pain is an unpleasant sensory and emotional experience. associated with or resembling that associated with actual or potential tissue damage. So, the, the key thing here is this is an experience, uh, unlike many things we deal with in medicine where they're objective, observable, like tissue pathologies, you know, so a, a thrombus in an artery, a broken bone, a, you know, a tumor somewhere in the body. What we're really doing here is we're. Engaging with someone's experience and trying to change it. And when you really think about what we're trying to do here, it's, it's actually quite challenging. But, uh, pain in a, in a protective sense, uh, is something that is actually very necessary for, for us, uh, when we, when there's actual tissue injury, our body is alerted to this and then we make behaviors to kind of get away from that, that threat, like a burning stove or, you know, a nail in your foot. But then often, often, Pain that is protective and adaptive can become pathological and maladaptive in many individuals for various reasons. So, what, there are various flavors of pain, but the two, I'm gonna talk about the different buckets. Um, the kind that, you know, is associated with tissue damage is the kind we typically think of due to some kind of tissue injury, a broken bone, um, a burn, etc. We're all used to this. But there are situations in which the nervous system itself is damaged or there's a lesion or disease, and then Independent of external stimuli, like a, you know, a hot, a hot surface or something, there are painful, um, there's painful neural signals being generated intrinsic in the nervous system that can be, that can cause a very debilitating kind of over the kind of condition called neuropathic pain. Um, this schematic here kind of highlights that The neuropathic pain can occur due to a lesion in the somatosensory, um, division of this of the nervous system anywhere along its length, which is from foot to brain. So from the, the nerves to the root, to the ganglia, through the spinal cord, brain stem and brain. Any one of these positions, there's. The possibility for neuropathic pain. Uh, what we typically encounter is a lesion or disease in the peripheral nervous system, nerves and roots, but, but this just highlights that anywhere in the nervous system, somatosensory nervous system could be an originator or a kind of cause of neuropathic pain. And this slide highlights again the complexity of the neur axis and that anywhere along the length. Could be a source. So as an example of a central neuropathic pain syndrome, um, spinal cord injury, multiple sclerosis, uh, these kinds of situations or a thalamic stroke can also lead to neuropathic pain, but we're going to focus mostly on the periphery today cause that's probably what all of us are seeing a lot more of. So, kind of the first step in in the identification and assessment of pain is putting it, you know, kind of categorizing it. And so historically there are really 22 categories recognized. No deceptive, which is the type where there is, that is pain that arises from actual threatened damage to non neural tissue, so NOA. Incision, all these conditions here on the, you know, various conditions where you have activation of the somatosensory nervous system, um, neurons responsible for pain detection, particularly nose receptors. Then you have the neuropathic condition we talked about, where there's a lesion or disease of this amount of sensory nervous system. And there's a list of uh indicate or kind of conditions there. Often there is a mixture of both things happening at once, so like in a sciatica, which I we we've kind of moved away from that term, but a a radicular pain situation, you have noseceptive pain from a degenerative spinal uh structure like a disc that, and that often is the the kind of cause of that localized back part, but then the part that is felt down the leg is due to um impingement and um kind of. rotation of the root. And so there's that that would be considered a mixed situation. And then, because not every condition uh falls into these two categories in recent years, the kind of pain research community has created this nosy plastic, uh, category, which is, is somewhat controversial and I, I, I personally don't use it within my kind of mental schema, but it's meant to capture some of these, these conditions that I'm sure all of you see like fibromyalgia, irritable bowel. Institial cystitis that don't have any particular um There's nothing observable by the methods that we have. It doesn't mean the pain is not the pain is what it is, but nothing observable, uh, indicating some kind of tissue damage, but it does indicate that there's altered, you know, altered activation of the, of the nosyceptive, uh, kind of apparatus. But, uh, I, I think for our purposes, kind of bucketing things into nosyceptive, neuropathic, and mixed uh can be very useful to uh guiding treatment. So what are common conditions presenting with neuropathic pain? Well, most of the time actually, there isn't an identified cause and we, we label this as idiopathic. Uh, but then when there is an identifiable cause, the number one, cause is diabetes by far. And then alcohol often patients who have chemotherapy, uh, develop a, a peripheral neuropathy, traumatic nerve injury, as one might see in a, in a motor vehicle accident or, um, you know, gun violence or, or incision, etc. uh disimmune, so various immu uh autoimmune. Conditions, uh, have associated uh neuropathies with them like Sjogren's syndrome. So Sjogren's syndrome has that as a, as a very common, uh, you know, fellow traveler, nutritional neuropathies like vitamin deficiencies like B12, B6, etc. and then infectious, uh, one that you, you all probably see commonly is due to shingles, and then for many people that resolved, but then for many others it does not. And that can become a post herpetic uh neuralgia. So what are the features of neuropathic pain? What, what distinguishes it? And, and so there's actually a variety of sensations that one can feel, and there's a there's a list here of of all of them, but the, the kind of common language is Descriptors such as burning, tingling, paresthesia, or um numb numbness is often a part of it, stabbing, electric shocks, and these are the kinds of words that should that should make your your minds think, OK, perhaps there's an issue here with the nerves themselves and not the non neural tissue, uh, kind of activating them. So what is, what is an approach that you could follow to diagnosing peripheral neuropathic pain? This is from a recent review I include here and I'll, I'll share my slides after this. But first is, do they have pain? OK. Then is it in the distribution of a peripheral nerve? There are many nerves, but often a peripheral neuropathic pain presents in a so-called stocking and glove fashion where people will they typically say their feet are having these symptoms, sometimes their hands, but often their feet, um. So at this point, you know, between a pain and a distribution of nerves, uh, that is kind of That follows a neuro anatomical uh pathway that should kind of tip you off, consider to peripheral neuropathic pain, then you do an examination if there are uh Loss of function and gain of function sign. So loss of function sign would be numbness. If you touch their feet and they don't feel it, that might be an indicator. If you use pinprick and they and they have altered sensation and they don't feel pin as sharp, another indication. Um, and this, this uh article goes into a lot of those maneuvers. You might use, but typically neuropathic pain has loss of loss of function signs, but then also, um, gain of function signs like some patients report if their skin, uh, or if their sock or their shoe brushes on their foot, it, it creates a painful sensation and that's called allodynia. Um, so if they have some of these symptoms in the areas that that kind of follow a a an expected neuroatomical distribution, one considers peripheral neuropathic pain. At this point, you may also use some additional instruments that I'm gonna share with you, such as patient reported outcome measures that can help kind of, uh, increase your confidence that they, they do or don't have a neuropathic pain syndrome. And then, uh, once you've kind of felt that this is, this is neuropathic pain, you want, then you might want to hunt further for the actual etiology of it when, when possible, which typically, Involves uh electrodiagnostic studies, some, uh, serological tests looking for things like, you know, the B12 uh hemoglobin A1C when looking for diabetes. Um, you may send for some advanced imaging if you feel comfortable with that, or you may send to a uh to a specialist like a neuromuscular uh neurologist, um, or, or, or a hand surgeon if you, if you think it might be an entrapment. For further workup and evaluation. So, some, some practical tools. You guys are the I put the dot phrases here that I use myself, and I, and I encourage you to kind of use this in your, in your workup. Um, you can, you see the dot phrase on the bottom there, you're welcome to take them from me in epic, but these are, this is called the DN4 questionnaire, and it's a validated questionnaire used around the world to um help you figure out whether the, the symptoms the patients uh are are are describing. are consistent with neuropathic pain. So neuropathic or or noyceptive. Like if it's not neuropathic, then it kind of by default uh falls into the noyceptive basket. And we actually use this as a, as part of our intake and this helps me to kind of funnel patients into my clinic or send them to my colleagues. Um, and so you could use this DN4 symptoms questionnaire on the right. There are 77 items and if the patients are using these descriptors, if they, if they're 3 or greater, uh, that is a high likelihood of neuropathic pain. So And and if and if less less than that, it doesn't completely exclude it, but your confidence goes down. Um, there's also an instrument that's more extensive here on the left that has some uh maneuvers from uh the physical exam that increase the sensitivity and specificity of this, but I think just even using the one on the right there, the DN4, uh, just with the symptom categories can be very helpful. And I encourage you all to use that when you're thinking about, oh, do I wanna do I think this is nerve or do I think this is um nooceptive. Uh, so the, uh, the special interest group of, of, uh, the IASP for neuropathic pain came up with, with a, with an algorithm here, and, and it kind of follows what we talked about. But first, there's a history of a relevant neurological lesion or disease and pain distribution is neuroanatomically plausible. If yes, it's it's possible neuropathic pain, then on your examination, are there sensory signs in the same neuroanatomically plausible distribution? Yes. And then diagnostic testing, which can include, these are all, a lot of them are specialist tests, but the ones that you all would be uh familiar with would be nerve conduction studies, which you can refer for and are, are a key part of kind of determining for sure that there's a neuropathic etiology. And then, uh, specialists. Tests that often happen with the neuro neuromuscular physicians are skin biopsy, which not every kind of neuropathy is detectable on um electrodiagnostic studies, an important one being so-called small fiber neuropathy, the where these, this, these are, these are the sensory neurons that are responsible for many painful sensations, but they're not detectable on electrodiagnostic studies. And, but you can see. A deficit of them or a reduction via a specialized skin biopsy, and that often is how we make these diagnoses. So, management, what can we do? So I kind of want to give you a broad overview of of my my at least my, my conception of what does a pain management or pain medicine specialist do. And when I talk to patients, I kind of, I have this, I have this broad overview of what really what can any physician in the world do, do for you? There are only so many things. And I kind of group and I, and I stratify them by invasiveness and risk. So, first, you know, on the first line is something that you all are very comfortable with. I think every physician should be, but recommendations for activity modification, exercise and directive therapies, lifestyle modification, and cognitive interventions, and whether that, and that's often with our, you know, allied allied clinicians, psychologists, uh, physical therapists, etc. I think almost everybody is suitable for that. The next step is pharmacotherapy, which is also a core tool to basically any, any clinician, and then I'm going to discuss further the uh specific uh pharmacotherapies that are suitable for neuropathic pain and have a good evidence base. But then, you know, as, as you're all probably aware, there are many patients who, you know, you do, you do the gabapentin, you do the duloxetine, you try a TCA, they're still their, their feet are on fire, their hands are on fire, they're miserable. At that point, that's when you can consider, I think, sending to us where we bring additional value. We have a a a um a large toolbox of procedural interventions and I'm gonna go into depth in a second, that can, can really move the needle for folks who have resistant pain. If, if the, if the stage 2 here of the pharmacotherapy works, not, it's not necessary to come see a pain management specialist, but often there are patients for whom the the first line agents and even second line agents are not uh sufficient. And then, you know, at the, at the on the far right is a structural alteration, which is basically surgery. If, if it's possible to uh identify a structural lesion that is causing a neuropathic pain syndrome, so for example, uh, a carpal tunnel syndrome, which is a median neuropathy, uh, median nerve neuropathy, and entrapment neuropathy at the wrist. Often a something like a carpal tunnel release where you kind of free up, free up that nerve and, uh, reduce the entrapment can often be a, a, uh, a, you know, a very durable and almost, you know, definitive therapy for many patients. But, um, this is kind of how I think of things and how you might also think of things with regard to a lot of medicine, but pain medicine in particular. I share, I'm, I'm not gonna go through all this, but I share here with you. I actually thought Up to date did a really good, a really good job, um. I, uh, with kind of a a algorithm for the management of chronic pain, um, forgive my typo there, that shouldn't be neuromuscular specialist, that should just be basically everybody, because what I want to emphasize is that, um, every, every clinician, I think, can do a lot of the, the first line things to help patients, which, uh, you know, begins with an assessment of what do you think their pain is, what kind, um, identify. Uh, other comorbidities like do they have sleep disturbances? Are there comorbid, um, psychiatric illnesses? Uh, are, is there, is there obesity? Uh, do they have difficulty, uh, engaging in exercise? There are a lot of non-pharmacologic therapies that can be first line for almost everybody. Um, and then further, uh, and this is where you can see the categorization kind of uh, matters. Uh, no. Type pain. So for example, a NOA, you know, uh, typically responsive to things like NSAIDs, um, whereas neuropathic pain, uh, is typically responsive to a different set of set of medicines, including tricyclic antidepressants, SNRIs like duloxetine, gabapentinoids, some sodium channel agents. And so I think really any clinician can, can, can take it through these levels, and I encourage you to do that. But then, after, after, uh, you've tried these things and uh a patient's pain is uh still, still present and and unresolved, that's, that is the point when you can consider kind of 2nd and 3rd line therapies if you're comfortable, or refer for uh pain, pain to a pain management specialist such as myself for evaluation and, um, you know, presentation of some of our advanced therapies that we're gonna go into. So, this is a nice treatment algorithm. It's a consensus algorithm from uh a group of pain physicians and and other clinicians dealing with neuropathic pain that shows a nice schema of basically what, what I, what I said there and kind of where we come in is at the, at the level of interventional therapies and neuromodulation, as well as targeted drug discovery. Uh, as you all know, once upon a time, opioids were liberally prescribed for basically every pain condition and things have really changed and I think on the clinician side, we're, we're much more reluctant, both, you know, kind of intrinsically so, but also constrained by, uh, by the law around um opioid prescribing. But I also I find The, the patients don't want it either. Like, I, I actually, it's, it's, it's very interesting, you know, I was starting my practice in 2024. The patients come to me explicitly saying, Doc, I don't want, I don't want any oxycodone. I don't want any morphine. So it actually makes my job in life a lot, a lot easier to not even have to cross that bridge. But I do think there is a time and a place and it's recognized, for example, like as a second line agent, tramadol, which is a kind of a mixed, uh, mild opioids. But there, it's not, there is a time and a place, and I think it's, we shouldn't throw the baby out with the bathwater, but much later in the algorithm than, than I think things historically were. Um, this, this graph on the right is a, is a really well-sighted and well done meta-analysis and, and kind of guideline of different therapies for neuropathic pain. Um, you can, uh, after, after this talk, refer to this in my slides and it's probably a lot of what you're already doing, but I, I refer to this uh very often. So, as I kind of mentioned, why, why, when and why to refer to a pain management specialist. So when the diagnosis is clear but unresponsive to treatment, so you've gone down the algorithm, you've tried all the things and the patient is not improving. Um, I A lot of my so my referrals come heavily from neurology, right? So they're very, very capable and excellent at uh everything through the phar pharmacotherapy, and, but there are still many patients who, you know, they have a clear diagnosis of one of the neuropathies we talked about, often diabetic or idiopathic, but they're just not responding. That's when patients come to me, um. Endocrinologists are also increasingly sending. I have a wonderful relationship with our endocrinologists. Some of, uh, also a lot of, uh, primary care physicians are seeing undifferentiated neuropathy in the community, but will often do the beginning workup and and make a definitive diagnosis and then. Send to me and this has been a wonderful relationship, uh, podiatry as well. But in all these cases, you have a clear diagnosis, but just the therapy has not been working. But then, you know, there's also diagnostic uncertainty. Yeah, they have pain in their feet, but it doesn't have clear neuropathic features, but I, I, I think I really think it is, or um. You know, a, a, a nerve conduction study comes back abnormal, but it's not within a clear etiology and the first line things have not been working. Uh, this is another time to, to send for evaluation. So let's talk about some of the things that we do. So I like, again, I'm I'm a minimalist when uh in in my kind of interventional approaches. So I I always will go with the least invasive, least risky thing first. And so one of the, one of the therapies that we do at Barnes West County is this topical capsain, also, you know, the trade name being Cuttenza. This is uh indicated for diabetic peripheral neuropathy and posterpetic neuralgia. Now, like many things, it probably will work for a lot of conditions, but often our hands are tied by the payers and they're very strict about, uh, the, the kind of approved indication. And so I've largely been using this for diabetic peripheral neuropathy, and there's been a steady stream of folks getting this, but it's a very I I. I feel like for anyone with DPN that has not responded to conventional therapies, this is kind of a no-brainer because it's very safe. Um, it's, it's literally a patch. The patients come in for 30 minutes, the nurses, uh, they, they clean the area, they put this patch on, the patients sit there for 30 minutes, uh, do whatever they like, watch TV, um, read a book, and then, uh, cleanse the foot and go on their way. It's repeated every 3 months, and there's actually the the studies of this of this therapy. have identified a cumulative effect that with each treatment, the, the, the, the benefit, the pain relief gets better. And interestingly, there's also been noted uh return of sensory function. So many of the things that we do almost every therapy that I have. Will deal with people's pain, so the, the tingling, the numbness, the no, sorry, the tingling, the burning, the pins and needles, but it will not resolve their loss of function, which is also very bothersome and leads to real consequences like you can't feel the floor, you, you'll often, you know, patients will often complain complain and suffer falls, or I can't feel the, the pedal on, on the gas when I'm driving my car. Most of the things that I have and most of the pharmacotherapies will not actually change. Anything about that. That's mostly a function of regeneration of the nervous system, if possible. But Ctenza has been shown to prompt that regenerative process and lead to some regaining of sensory function. So, uh, I, I think this is a unique and, uh, therapy that I, I, I wish I could use more broadly, but if I, I bring this to your attention, if you have patients with diabetic neuropathy and they're seeming like they might be good candidates for a topical like this. Please send them our way and we're happy to do it. And I'll just say, actually really, I think any medical practice could do this, but what, what is limiting when I talk to others and why I think we're equipped to do it and other other facilities aren't is it actually takes space so you so you have to have a patient in a, in a room of somewhere for for at least 40 minutes. Um, there's, there's also kind of staff concerns like, so we have like at least 2 nurses working on the patient like uh cleansing and applying and. And also checking vitals to make sure that there's no transient increases in blood pressure or or heart rate. And so it's just kind of like logistically difficult. but we have the resources and the space at at uh and and really a nice uh efficient pipeline now, uh, and workflow at Barth West County Pain Pain Management Center, uh, to do this. So, but, but if I just say this that if this is something that you think you might be useful in your practice and you have the ability, there's nothing stopping you, and, and I would encourage you to consider. Um, infusion therapies. We don't have a lot of these, but there are some, there are a couple tools in our tool kit that we use in the pain management group, uh, that are is a specialist technique, and I would not recommend that anyone else do unless they had a trained, uh, professional, probably an anesthesiologist nearby, uh, but we do lidocaine infusions, so lidocaine is a local anesthetic, uh, I'm sure everyone here is familiar with. But typically we're injecting it somewhere. But um it's also, it also is used sometimes in cardiology for dysrhythmias, and it's used heavily in, in kind of acute and chronic pain practices as a, as an analgesic therapy. So this was actually on the news about a year ago. This is our clinic down at the camp. That's actually the only site where we do this because it requires like very close monitoring for uh cardio cardio. Pulmonary, um, and, and toxicity, cardiopulmonary dysfunction and uh toxicity due to local anesthetic. But, uh, patients come, they sit in our our infusion suite there, and they're hooked up and they get a low dose of lidocaine. And you know, what is the benefit of this? You might, because lidocaine's duration of action is, you know, only a couple of hours. Admittedly, like the mechanism is not entirely clear in some way, shape, or form, it probably has to do with, um, you know, inhibition of sodium channels because that's what lidocaine does, but The duration of effect for some patients can be beyond the expected, you know, number of hours, like, so people will say they have days to weeks of benefit, and it can really be like life altering, and it's fairly, fairly safe, um, and, you know, with the appropriate monitoring. And so we, we will do this quite a bit, and for some patients it can be life changing for others it's, it's, it's lackluster. And like so many things, one has to just take an empirical approach. You try it, you see if it works. If it works, great, we do it monthly. If it doesn't, we don't do it again. But this is something that we can uniquely offer at the pain management group that, uh, I, I bring out quite a bit as for my patients with neuropathic pain, especially when it's diffuse, when they have whole body uh neuropathic symptoms. So what about interventional therapies? So kind of the, the big buckets are injection therapies and uh local anesthetic and corticosteroids around nerves. This is typically for things like entrapment, neuropathies or a neuroma. There's neurolytics, uh, where either thermal or heoneurolysis is performed to uh disconnect parts of the uh body from the nervous system, if there's a kind of painful locus. Uh, neuromodulation, we're gonna talk a lot about which is various kinds of electrical stimulation applied to the uh to the nervous system to alter and interfere with, uh, pain, pain generating signals. Targeted drug delivery, which is intrathecal pump therapy. And then increasingly minimally invasive structural interventions like a nerve entrapment released or spinal spacers for like uh lumbar spinal stenosis. So nerve modulation, uh. The kind of three major categories are peripheral nerve stimulation, spinal cord stimulation, and dorsal root ganglia stimulation. This review I cite here has a lot of really good information about the the ways in which, uh, not just pain specialists, but many kinds of physicians, uh, neur neurosurgeons, neurologists, um, pain specialists, physiatrists are using electricity to alter the, the nervous system function in some way for some therapeutic benefit. And uh I think this is a really um a really interesting uh field, and we're going to see a lot more of it in the future. So spinal cord stimulation is probably the most mature form of neuromodulation uh in pain management. It's, it, it was 1st, 1st kind of discovered as a therapy in the 70s by some intrepid uh neurosurgeons who, who kind of took the, took the plunge and tried this. And then it's really matured, I'd say since like the, the early 200. Thousands, both hardware wise and also programming wise, software-wise as well. But in, in all its forms, it it it entails the placement of electrical wires, uh, SES leads, uh, on top of the spinal, um, the epidural space aligned over the dorsal columns, which is where Which is where the uh certain, certain kinds of somatosensory neurons run, and the, I won't, I won't go too deeply into it because to be honest, I, I don't know that we fully understand how it works, but the, the kind of classical, uh, teaching is that the, the electrodes activate low threshold mechano receptors, which are touch neurons, which Run in the dorsal column. And by doing so, they, they, that activation of those touch neuron axons inhibit the, the, the inflow of afferent painful signals from other kinds of sensory neurons, uh, which we call ADelta and C fibers. The, the kind of common experience analog to this, and I think it's what what prompted people in the first place to consider it, was when you, when you, let's say you, you stub your thumb with a with a hammer. Kind of reflexively, you actually start rubbing it with with your other hand, which is when you really think on its face of it, why, why do we do that? Why would you start putting more stimulus to an area that's been heavily stimulated, but the non-nxious touch sensation will interfere at the level of the spinal. Dorsal horn with those painful afferent signals coming from the stubbed thumb and that's how it's thought that spinal cord stimulation works. Of course, it's more complicated than that. There have been uh studies in animal models implicating glial cell activation, which are non neuronal support cells, um, you know, uh. Activation of different cortical regions, right, because that electrode doesn't just send signals into that dorsal column, it will, it will activate neurons all the way in the cortex and subcortical areas that affect the uh kind of the affective component of pain. So there's a lot more going on, but I think ultimately, Efficacy wise, which is what many clinicians care about as long as it's safe and efficacious, we can kind of, you know, leave all the mechanistic details to the back burner, uh, uh, and, and learn as we go along, as long as we think it's not hurting anybody. And I think this being a very mature technology for, you know, decades now in use, uh, I think that that that that is the kind of consensus feeling. But it's definitely not something to be taken lightly because you'll you'll see now. Um, so here's a, this is me actually. a case earlier this year on a patient with small fiber neuropathy. It involves the uh insertion of, of, of hardware into the epidural space, right, where there's always an infection risk but potentially or neurological injury, but done safely and by train and fellowship trained physicians such as myself and my colleagues, it's actually a very safe and straightforward procedure, um, and So the an electrode is is threaded through the epidural space, um, and the, and it lies at top of the dorsal column. Now, we do this in two parts. We do a trial first. So what's really nice is that you don't have to fully commit to something living inside of you for the rest of your life if it's not going to work. And so what you see here in the office is a trial procedure where we put electrodes in, and then they're left, so they, they protrude through the skin, you know, they're coming out of the skin and then the battery for it is placed on the outside. And the patient wears this for 7 days and is able then to experience what it's like to have this in. And we're looking here for kind of a criterion of at least 50% relief, likely more in their, in their, in their pain. To give us confidence that we should proceed to a permanent implantation. Some colleagues and I use this now analogy, this is like a a a a pacemaker of the spine. It's actually the same very similar hardware and the same kind of companies that are doing this. There's a pulse generator, and then there's a, and then there's a a wire. But I, I, in part of my practice, I, I've really, I've implemented these patient reported outcome measures so that instead of just kind of having a, a vague on like, oh, what percent relief did you get, we have a kind of Comprehensive assessment of all the different areas of life that are affected by pain. Um, and so this patient in particular, I, I really consider this a real win. Pretrial, she had severe physical dysfunction. Her sleep was, was, was one of her major concerns. She wasn't able to participate in, in in social roles, and pain was really interfering with her life. And you can see that even in 6 days, there was a, a great normalization of many of these things. And when I proceeded with the permanent implant, she came back to me. She's a young woman. She was 37, she said, I almost feel normal again, which to me was one of the best things that one can hear. Now, full, full being fully transparent, they're not all slam dunks all the time like this. Not every trial looks like this. And if you're being a judicious and careful physician, you will not proceed with the implant if someone isn't getting this kind of benefit. But I use this as kind of an example of what's possible for people who have tried everything else and are living in in agonizing pain, but there is something that can be, can be helpful. Um, this is, this is a study for DPN. So like everything else, um, there are indicated they're kind of on label FDA indications for spinal cord stimulation, and they, and they can be pretty restrictive. But diabetic peripheral neuropathy is one of the recognized, uh, um, on label indications. And the reason being studies like this where, um, there was really tremendous relief uh in a in a durable fashion for patients using uh this certain type of spinal cord stimulation. Um, and then You know, this is on the left is the, they did a randomized stage and then did a crossover as well, and you can see that there's continued benefit in both in both groups after after the crossover. So I think that's why the spinal cord stimulation became on label for things like DPN um and I I've used it now with several patients with the DPN and it's been, it's been very effective. Um, other forms of stimulation. So, SES is the more mature technology, new kid on the block is peripheral nerve stimulation. Actually, it's very old, people have been thinking about this for a long time, but in its implementation, the development of hardware that was suitable and comfortable and easy to use in the clinic really only is probably the last 7 or 8 years, and I like this one, I use this one particularly on the top here called Sprint where you use ultrasound guidance typically, sometimes fluoro, but ultrasound guidance to identify a peripheral. Nerve and you put the lead, um, through the skin next to the nerve. And then in this instance, there's an external pulse generator. So, the sprint device is a temporary 60 day device. It's not permanently implanted, which kind of I think eases the barrier to entry for a lot of folks. They're like, OK, you know, worst case scenario, it doesn't work. I'm not committing to something being inside of me, it's very safe, but actually, it might actually be very beneficial. And so I use this quite a bit for patients with a localizable peripheral nerve problem. Um, the evidence for, for both of these is growing. Um, on the left is a study with Sprint where they did it actually for phantom pain, which is one of the areas where I use this the most, and you can see really great, uh, benefit in the kind of uh pain responder group, um, for, uh, phantom limb pain in the setting of amputation. And then the Nalu device which I showed over here, which is a kind of semi-permanent one, where the leads go under the skin and the pulse generator is external, but it's, um, but it's a um it's a wireless one. They had an all comers kind of neuropathic pain setting where they did things like Mono neuropathies, median neuropathies, certain types of shoulder related, uh, neuropathies, and they also saw a great benefit out to 6 months, and I, I, I know that they're continuing to collect data to look for the long term outcomes, but I think peripheral nerve stimulation has really changed the game for the treatment of pain, and um it's something that I use quite a bit. The indications are symptomatic relief of chronic intractable uh pain post-surgical and post traumatic, symptomatic relief of post-traumatic pain and symptomatic relief of post-operative pain. So really very wide uh indications and and and in my view, and kind of the way I treat is if, if there's a localizable nerve that I think is the conduit for someone's painful condition, and I can safely put the lead there, I will typically uh offer that and, and it's been quite effective. Kind of at the end of the line is intrathecal drug delivery. This is actually not a procedure. I was trained to do this. It's not something I do routinely. The reason being, it's, it's a, it's a very, um, I mean, one, this is invasive like other things we do, but it also requires continuous kind of uh upkeep and maintenance. So the spinal cord stimulator, you, you put that in and you put the, the pulse generator in and, you know, so there's some post and uh post-op, you know, care and we. Make sure that the incisions are healing well. But that can be something where we do it and then you don't have to have frequent engagement, uh, you know, month after month for it to work. It's just kind of, it's in the patient and they, and the battery lifetime is like a, a decade for some. Whereas intrathecal drug delivery, there, there's a pump and a finite amount of medication. The medication for pain, the approved ones being mostly, I think, uh, morphine and Zaconitide, but people also put other things like. canine or or hydromorphone in there, but it has to be refilled. There's a finite amount. And so, you know, in a, in a setting where you're doing this on, uh, for patients with neuropathic pain, or any kind of pain for that matter, they're having to return to your clinic maybe every 30 to 60 days for a refill of this in a, in a percutaneous way. And so a lot of, a lot of pain physicians, you know, just don't make this part of their practice because it requires a lot of infrastructure and engagement, uh, ongoing engagement. Um, to, to do it right, but we do have physicians in our, in our BJC system here who, uh, do the, who are actually nationally recognized experts, actually Doctor Chris Christopher Bureau up at um Christian Northeast. And so, I know one of the nice things about working in a place like, you know, the BJC WaU system. is having really great colleagues whom you can refer to when you think there's a therapy that that a patient needs, but you yourself are are not equipped or wanting to do it. And so, uh, I keep this in my arsenal, but it's not something that I'm doing, but I want you to just to be aware that even beyond neuromodulation, there is an additional therapy that can be very effective. So future directions, where, where are we going? So actually, uh, this is actually not even the future, this is the current, but, uh, last month the FDA approved for like the first time a new um pain medicine called Suetragine, the trade name is Dernavi, it's from Vertex Therapeutics. It's a, it's a new, it's a new implementation of an old class of medicine, so We have many non-specific sodium channel blockers. Sodium channels are responsible for action potentials that are, you know, the kind of the basis of all neural signaling. Lidocaine is a non-specific sodium channel blocker. Carbamazepine is a, you know, is an oral form of that of a non-specific sodium channel blocker. Many uses for sodium channel blockers in in various kinds of uh medical settings, but what What is special about strogen is that it's, it was, it's engineered or or kind of tailored to a particular subtype of sodium channel that is specifically expressed in those pain, pain, um, you know, associated neurons called nociceptors. And so you can, it's, it's instead of a hammer, it's a, it's a scalpel. And, and so this is very exciting. Uh, there was, uh, there's a New England Journal paper showing the, uh, the clinical trial for acute pain settings. You're probably are, some of you may have even had patients already ask you about this. The, the thing is, it is a very new med and like all the new meds, it's gonna take some time to kind of find its place in the wild, but it's only right now approved for acute. Indication. So perioperative settings, you know, maybe, uh, non or non non-operative acute settings, like maybe like a fracture. I mean, the, the actual indications in the study were abdominoplasty and, uh, bunionectomy. I actually really don't know like how broad people are going to be able to use this, you know, in their interactions with the, the payment system. etc. But it's really exciting and I think you're gonna see a lot more of this. And I'm actually also, I, I myself have been involved in this in a little way. I'm a site investigator for the phase 3 trial of this in diabetic peripheral neuropathy. So the, the company Vertex is wanting to expand this to other conditions, and I'm excited to see where it goes, but um you all will be hearing about this, I'm sure. Um, kind of future stuff. I mean, this is, this is like probably years, like in the making before it becomes a thing, but, uh, there's talk of, and I, I've been asked to be an investigator, for example, for gene therapy for, uh, certain kinds of neuropathic pain where you deliver a payload in a viral vector that suppresses one of these sodium channels. So this is very exciting as well. I don't know if this is ready for prime time, but it it might be something that in 5 to 10 years we're talking about. And then personalized therapies. This is something that my lab is working on, but, um, you know, part of, part of being part of my clinic is the patients also are able to have opportunities to interact with and engage in the research mission, which is to figure out why these folks are feeling pain and see if we can come up with anything better for them. And so this is an example of where, uh, another group, this is not me, but you take blood cells from patients if you know, I consented part of a research study, but you can actually make kind of surrogate neurons. Uh, in a dish from those individual patients and run end of one, drug studies, you know, using, uh, different compounds. And in this case, I thought this is such a cool example of what, what's possible. They took a patient with a painful small fiber neuropathy, made personalized sensory neurons in a dish, and used a bunch of compounds and actually found that this patient's neurons were the activity was suppressed by the FDA or the approved, um, medicine glucosamide. So, I think something like this is the future of my lab is actively working on these kinds of things. So, you know, as you're thinking about maybe sending your patients to me, which I, I'd be honored to have that opportunity, there's also the opportunity to learn more about these conditions to help push the needle uh forward. So, You can how to, how to work with me if you'd like to send your patients. Um, so I'm over at Barnes West County, uh, a, uh, ambulatory referral to pain management and, uh, putting my name in. Uh, I, I'm there, well, I'm there once a week, but it's a, it's a dedicated clinic, and I, I see these conditions here, uh, mostly I'm focused on neuropathies, uh, of various flavors. Um, I have a Comprehensive evidence-based approach that I think is, uh, you know, tailored to this, this particular problem. And then the treatments are the ones I told you about and opportunities for research, um, uh, to, for, for the patients to either be part of investigational trials like the Suetragene one or some of the thing kind of more pathogenesis focused things that I'm doing in my lab. So, uh, I, I welcome. Any questions, uh, if you have patients that you think that you're thinking about or you have, uh, you, you, it's a difficult problem and you just want some guidance, I'm happy to uh to engage that and entertain all all questions so you can reach me by email or in Epic. Um, I'm at Barnes West County on Thursdays and every other, every other day of the week I'm here at this beautiful building downtown. So thanks for your time. Thank you so much, Doctor Tremes. I appreciate that. Um, there is actually a question in the Q&A. Um, what is the mechanism of increased BP and HR by I I don't know if you can say, yeah, thanks. Seems like a lot of monitoring for a topical. Yeah, I think, I think, I, I think, I think the mechanism is actually that, you know, so capsaicin is the hot peppers, like the compound that makes your mouth hot when you eat peppers. And, and so actually it's kind of paradoxical. Why would something that actually makes you feel a painful sensation be also analgesic? Uh, the mechanism is that you activate these neurons that express the receptor for capsaicin, the receptors called TriP1, and so you transiently are actually activating neurons and so it can be a painful sensation. And so when, when the body detects a painful sensation, there's a reflexive autonomic response, so increased heart rate, increased blood pressure. It's transient though, like it goes like, like it should only be for the duration of the treatment and according to the literature from, uh, from the clinical studies of that, no more than 1010, you know, 10 units on the on systolic. But that's, that's the mechanism by which it happens. It's going to be noyceptive afferent inputs causing a reflexive autonomic response. What about the older Casasian cream Sorex HP? I don't know about that one, but I'll say that that you can get capsicin cream over the counter. It's just a matter of percentage, just like lidocaine. So Q10s is 8%, and that's much I think that's higher than the most you can get um uh over the counter, which is 4 or 5%. I don't know about this particular one, but Q10s is the the one that is widely used for this purpose now, it's a patch. Any other questions? I'm not seeing. And if you all have any questions, I I'm going to send out an email after this program, and I will have um email addresses on there. You can also email me with your questions, but um if it's OK with Doctor Tremay and I'll put his email address on there as well. Well, I, I actually, I do see one question, Nicole, from, uh, Michael Mulligan. Can you reliably establish DPN? Is it any different than idiopathic, but they have diabetes? Does it matter for treatment strategies? Great, great question. So there are diagnostic criteria, uh, for diabetic peripheral neuropathy, but it's, but, but it's typically that the patient has diabetes, um, and, uh, that they, that they have pain in that typical distribution, um, and then If it's supported, if it's supported by things by by things like electrodiagnostic study that increases confidence. So there's actually a Toronto consensus, um, kind of criteria for DPN. Now, to your question of how is it different, uh, does it, does it matter putting that label on it? Great question. In reality, this is my honest appraisal. I think most neuropathic pain syndromes share, have shared mechanisms, and so, What works for maybe DPN would probably work for other conditions as well. And similarly, what works for other neuropathic conditions will also work for DPN and we and we do this right and we're we're already kind of, uh, confirming that, that feeling by the way we use things like TCAs and do a lot of our first line pharmacotherapy. But where it actually matters, like why. The label matters is honestly about is about authorization. So DPN is an indication for a lot of these things that gets the the payers are willing to agree to. So, um, like I, I've talked a lot about Cuttenza. I would love to use it in idiopathic peripheral neuropathy or chemotherapy induced. And there are folks in other parts of the world where they don't have these restrictions doing that. But if I, if I, if I try to use Qenza, let's say, on someone with a chemotherapy induced neuropathy, their, their insurances will often say no. And so the reason to care about the DPN label, apart from being diagnostically accurate, um, is is is largely around what you're permitted to and able to do in your therapeutic toolbox and for DPN it's probably the the largest. So that's the kind of the real world pragmatic answer as well. And then there was one other question in the Q&A also. Are you familiar with Panics M E T A N Y X, and do you use it. Um, I've not heard of that. Uh, it sounds like a trade name for something. Um, if, if the, the question asker can elaborate on what it is, I, I can comment maybe, but I've not heard of that. OK. But I'm happy to answer any questions by email or Epic at any time. And I'll definitely, I'll make sure that your um email address is on the follow-up email so they can send you any questions. Right. Thank you so much. Thank you.
