Central Neuropathic Pain With Dr. Charles Argoff

In the patient populations treated by neurologists, central neuropathic pain develops most frequently following spinal cord injury, multiple sclerosis, or stroke. To optimize pain relief, neurologists should have a multimodal and individualized approach to manage central neuropathic pain. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Charles E. Argoff, MD, author of the article “Central Neuropathic Pain,” in the Continuum October 2024 Pain Management in Neurology issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Argoff is a professor of neurology and vice chair of the department of neurology, director of the Comprehensive Pain Management Center, and director of the Pain Management Fellowship at Albany Medical College in Albany, New York. Additional Resources Read the article: Central Neuropathic Pain Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Full episode transcript available here Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Charles Argoff, who recently authored an article on central neuropathic pain in the latest issue of Continuum covering pain management. Dr Argoff is a neurologist at Albany Medical College where he's a professor of Neurology, and he serves as vice chair of the Department of Neurology and program director of the Pain Medicine Fellowship Program there. Dr Argoff, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners?  Dr Argoff: I'm Charles Argoff. It's a pleasure to be here and thank you so much for that kind introduction. Dr Jones: I've read your article. Many of our listeners are going to read your article. Wonderful article, extremely helpful. Closes a lot of gaps, I think, that exist in our field about understanding central neuropathic pain, treating central neuropathic pain. You now, Doctor Argoff, you have the attention of a huge audience of mostly neurologists. What's the biggest point you would like to make to them, or the most important practice-changing advice that you would give to them? Dr Argoff: I think it's at least twofold. One is that central neuropathic pain is not as uncommon as you think it might be, and it occurs in a variety of settings that are near and dear to a neurologist's heart, so to speak. And secondly, although we live in an evidence-based world and we want to practice evidence-based medicine - and I'm proud to have formerly been a member of the Quality Standard subcommittee, which I think has changed its name over time. And so, I understand the importance of, you know, treatment based upon evidence - the true definition of evidence-based medicine is using the best available evidence in making decisions about individual patients. And so, I would urge those who are listening that, although there might not be as robust evidence currently as you’d like, please don't not take the time to try to treat the patient in front of you o r at least acknowledge the need for treatment and work with your colleagues to address the significant neuropathic pain associated with that central neurological disorder. Because it can be life-changing in a positive way to make even a dent and to really work with somebody, even though not clear-cut always what's going to work for an individual patient. Dr Jones: Well said. I'm glad you brought that up. So, to put it a different way, absence of evidence is not an excuse for absence of treatment. Right? Dr Argoff: Exactly. And I think that, I hope that we would agree that especially in neurology, what we do is about as far from, ‘Yep, you've got strep throat, here’s that antibiotic that's going to work for you and all you have to do is take the medicine.’ I mean, most of what we do is nowhere near that.  Dr Jones: It's complicated stuff. And this is a complicated topic. And I'll tell you, I learned a lot reading your article. I think most of us in neurology and medicine, when we hear the term neuropathic pain, it feels roughly synonymous with peripheral generators of that pain, such as diabetic neuropathy or posttraumatic neuralgia. But as you mentioned, there's central mechanisms for pain generation. How is it defined? What is central neuropathic pain? Dr Argoff: It's defined as pain caused by a lesion or disease of the central somatosensory system . Though neuropathic pain in general is pain associated with the lesion of the somatosensory system; and to your point, that can be peripheral, which of course is outside the spinal cord, or brain or central, which is within the spinal cord or brain. And central neuropathic pain is defined specifically as pain caused by a lesion or disease of the central somatosensory system. That's either brain or spinal cord. But there's an interesting follow-up, and I'm going to ask if you could remind me because I know we're talking about definitions now, but I'll just bring something up and we can come back to it. What's interesting about that is that my - whoever 's listening, that's not to say that they're not connected. And in fact, they are very much connected. And there's very new work, which I included in the article, down at Washington University in Saint Louis, that suggests you can actually affect central neuropathic pain by addressing peripheral input to the central nervous system. If you remember Ken Casey at the University of Michigan at the World Pain Congress in Vancouver, British Columbia many years ago, he ended his talk on pain with a limerick, of which the last line was, Remember, there ain't no such thing as pain without a brain. And so that kind of summarizes that. Dr Jones: Well, and it goes both ways too, right? We know that there's some central sensitization that can happen with peripheral generators, right? So we really have to think about the whole circuit. Dr Argoff: Yes. And that's been sometimes the bane of my existence as a colleague of others and a sometimes debater. Is the pain central? Is it peripheral? Well, it's everything. And it's important to know as many of the mechanisms and many of the targets that you could use for treatment so that you can affect the best outcome for your patients. Dr Jones: Yeah, so - and you mentioned in your article what some of the common causes of central neuropathic pain are. What are the big ones in your experience?  Dr Argoff: So, the biggest ones are spinal cord injury-related pain, MS-related pain - and I'd like to come back to a point and just if I do the third one - and central poststroke pain. And what struck me, I think Tim Vollmer published a survey about the incidence, the prevalence of ongoing pain in patients with multiple sclerosis. And it blew my mind several years ago because it was incredibly high. Like in this survey of MS patients who, you never hear about pain, you hear about these modifying treatments, all the wonderful expanses that have been made. I mean, like seventy something percent of people say they have moderate to severe pain. And when you think about how sensory processing occurs, it makes perfect sense that a demyelinating disorder is going to interrupt the flow of information for a person to feel normal.  Dr Jones: Yeah, I think it's a good example of, there are things that we tend to focus on as clinicians where we worry about deficit and function and capacity. But if we're patient-centered and we ask patients what they care about, pain usually moves up higher on the list. And so, I think that's why we, it's maybe underrecognized with some of those central disorders, right? Dr Argoff: I think so, and I and I think you hit the nail on the head that - and we're also trained that way. I tell this to my patients very often so that they are reassured when I examine them and I say, and I tell them that everything looked pretty OK. It's not a medical term, I understand that. Because what we do in a typical neurological exam, even if it's detailed, doesn't really address all the intricacies of the nervous system. So it's really a big picture and sensory processing and especially picking up sensory deficits; you know, we use quantitative sensory testing and research studies and things like that, but bedside testing may not reveal the subtle changes. And when we don't see overt changes, we often think - that can lead someone to think that everything is OK and it's not. Dr Jones: So, when you when you see a patient who you've diagnosed with a central mechanism, so central neuropathic pain, how do you approach the management of those patients, Dr Argoff? Dr Argoff: I always review what treatments and what approaches have been addressed already. And I see if - a handful of time, we actually just submitted a paper for publication regarding this in a group of patients with pelvic pain who had untreated, difficult-to-treat chronic pelvic pain, seen all the urological kinds, gynecological things. Look, we picked up two patients who had unknown MS. So, it's just interesting when it comes down to that level. And we also picked up some patients who had subacute combined degeneration. So that's another central kind of disorder as well. Again, the neurologist in us says to make sure that we have specific diagnosis that underlies the central neuropathic pain. And so interestingly, of course, for somebody with MS - or even though it's uncommon, it could be more than one. Somebody with MS might have a stroke, somebody with MS might have a cord injury due to cervical, you know, joint disc disease. Not to overcomplicate things. Know the lay of the land, know the conditions, know what you're battling and lay out so that you can treat the treatable; you want to treat whatever you can correct? So, for MS you simply want to have the best disease-modifying treatment on board, tolerable and appropriate for that person, and so on. And then you really want to take a history of past treatments - and your treatments can be everything and anything, including behavioral modification, physical rehabilitative approaches, as well as pharmacologic management. That's - as I think I put in my article, we concentrated in the article on pharmacologic management because honestly, that's what most patients are looking for, is ‘what can we, what can you do to help me now, in addition to what I can do myself.’ And that's what we typically think of. There are also some more interventional approaches, invasive options, that have developed over time. And of course, those are the ones, some of them, especially in neuromodulation, that we have the least information about, but it appears somewhat promising.  Dr Jones: No, that's exactly what we need to hear. And you also mentioned something that I think is important. This is a common theme throughout the issue because I think it's true for the management of many different types of pain and interdisciplinary approach. In other words, not just honing in on pharmacotherapy or neuromodulation as a one-size-fits-all magic pill, right? So, that - tell us a little bit more about that interdisciplinary approach and how that's important for these patients. Dr Argoff: So, let me back up and give an example. Let's look at Botox for chronic migraine. So, the pre-M studies that led to the approval of Botox for chronic migraine: two treatment sessions versus two random, two placebo session in different patients. The mean headache frequency was, let's say, fifteen to twenty in each group. It was like seventeen, eighteen, something like that. But the mean pain headache day reduction was somewhere between four and five after two treatments compared to a lesser, a lower number in the placebo group. So, if you think about that, that means that you went from nineteen, let's say, to fourteen, thirteen, or twelve. Want to be generous, eleven or ten. But that means that person, everyone 's happy. We use treatment. We have better data than that because the longer you use it, the better it gets in general, but it means that people are still going to be symptomatic. So that drives home in a different painful disorder the importance of yes, treatment can be effective, but it's not the only treatment that a person is going to likely need. And so, I think that's what's so important about multidisciplinary approach. I- we may affect positive changes, reduction in pain intensity with a particular pharmacologic agent, but we don't anticipate it's like taking an antibiotic or a strep throat, not curative. And so, we want to, early on, to explain that logically, methodically, step by step. There are many options for you and we're going to, you know, systematically go through them. And I may need to call in some colleagues to help because I don't do everything. No one does everything, right? But don't feel as if there isn't any hope because there is. If we were to use intraspinal Baclofen for someone who has painful spasticity following a stroke or a spinal cord injury, combining that with physical therapy might give more effect, maybe synergistic. Some targeted muscles, some local muscles may not respond as well to the intraspinal Baclofen, so is that - what can we do? Well, we could use oral agents or we might be able to target that with botulinum toxin, and so on and so forth. So it's limitless, virtually, in what you can do. Dr Jones: There's kind of setting expectations and letting people know that you, you're going to need a lot of different approaches, right? To sort of get them the best possible outcome. Dr Argoff: Yeah, I think that's so important. And of course, no matter what we try to set out, there are going to be individuals - for those of you who are listening, we all know - who expect to be cured yesterday. That might be challenging for us not only to actually complete, but also, it's challenging for some individuals to appreciate that we're with them, we're going to work with them. It’ll be a process, but we've got your back. Dr Jones: Great. And you know, this is a question that I get all the time from patients and from other clinicians is, you know, what about cannabinoids? What's the role of cannabinoids for the management of central neuropathic pain? Dr Argoff: First, I'll say that the short answer to that is we don't know. The second part of my response would be, there is new evidence that it might be helpful in the acute treatment of migraine. And I'm happy to say that the editor of this edition of Continuum is the person who developed that evidence, and it's been recently presented at the American Headache Society. But the challenge and the conundrum that we all face is, everywhere within our nervous system where there's pain being processed, there are endocannabinoid receptors. There also happen to be opioid receptors, but that's a separate issue. And the endocannabinoid system, the peripheral or central, you know, CB1, CB2, is very, very important, but we haven't figured out a way of harnessing that knowledge in developing an analgesic, an effective analgesic. And part of that is that there are so many chemical agents that have cannabinoid properties and there are different… the right balance has not yet been found. But even the legalization, the available of medical cannabis, hasn't led to a standardized approach to evaluating if a preparation does help. And that's part of the conundrum. It's like saying, ‘does medicine work?’Well, yeah, sometimes. But which medicine? Which receptor? How do you harness the right ratio between TBD, THC, other active agents, et cetera? And I think maybe as we go forward in the future, we’ll be able to do that with - more precise. I mentioned Dr Schuster's study in which he had defined ratios of THC effect and CBD and was able to clearly show effect based upon that. But the average person going into a dispensary doesn't really get that. We don't get to study that. Each person's an NF1  and it's not very helpful to understand how to do that. I would say, as I'm sure you remember, there was a practice parameter that was published probably over a decade ago about using cannabis symptomatically in different neurological disorders. And I believe that it was what they studied or what they reviewed was helpful in MS-related urinary discomfort and spasticity, but not necessarily pain.  Dr Jones: And we're still in the early days of studying it, right? Dr Argoff: Yes.  Dr Jones: That's part of the point, as we got started late and we're still waiting for high-quality evidence. And I guess, if you look at the horizon, Dr Argoff, or the future of management of central neuropathic pain, what's going to be the next big thing?  Dr Argoff: One of the joys of being asked to get involved in a project like this is that inevitably we learn so many new things because, you know, that's when anyone says, oh, you must be an expert, I say, I don't know anything because I'm always learning something new. One of the reasons why I moved to Albany Medical College about seventeen years ago was to be able to further my interest in studying why people benefit from topical analgesics by working with a scientist at Albany Med who studied keratinocyte neurochemistry and its impact on pain transmission. And that's a separate issue, but it indicates my love for the peripheral nervous system. And one of my thoughts historically, that is, what the central nervous system processes is what it processes and it might get input, as you mentioned earlier, from the peripheral nervous system, so that topical agents could be dampening central mechanisms. And lo and behold, as I was doing research for this article, I learned that people doing peripheral nerve blocks - so blocking peripheral input at the into the spinal cord - at Washington University, Simon Guterian and colleagues, demonstrate that they could give prolonged benefit from central pain by blocking peripheral input. And that's wild because certainly the nervous system is a two-way street. It's an understatement. What I really found amazing was that, again, blocking input helped the injured central nervous system to behave better.  Dr Jones: That is kind of cool to think about. And I'll tell you, as editor of the journal, one of the funnest things is getting to learn all about neurology, including pain and including central neuropathic pain, when in the end you're doing all the work, I just get to sit here and enjoy it. And you're a program director of a pain fellowship. What's the pipeline look like? Are neurologists more interested in pain than they used to be?  Dr Argoff: I'm happy for this. We are seeing more and more applicants from neurology into our pain management programs. I would say… I was going to say tragically. If I say tragically, it's because what specialty better understands how to diagnose, figure out, assess, come to a conclusion? You can't have pain without your brain. It's always amazed me that more neurologists weren't interested, and I understand the background and such. Just like in migraine, it's only advances in understanding mechanisms of migraine that allow neuroscientific advances that are leading to great therapeutics - that's happening and increasing in ‘pain.’ Today, as program director, we had our fellowship interviews earlier today and three of the nine applicants that we interviewed were neurologists. Last week, I think we interviewed two or three also. That would not have happened five years ago or six years ago. And if you think about it, we can not only diagnose, quote-unquote figure out what's happening, but we now, with pain management training, we can offer people a variety of both invasive and noninvasive options, all while understanding what we're doing with respect to the nervous system in a way that's different than the other specialties that typically go into pain med. And that's such - for me, it's a beautiful experience and something I really enjoy doing. There isn't a neurological condition in the most part that either doesn't have pain associated with it or doesn't have mechanisms that overlap. If you think about epilepsy, and please don't think I'm crazy, but epilepsy is associated with disinhibited hyper-excitatory behavior, just to put it loosely, among certain neurons. That's what pain and neuropathic pain is about too. And you, in fact, we know that several mechanisms since now what medicines are used for both. But what was interesting since, if I may just go back to another point, one of the advances since I brought up the migraine that's very exciting is the whole story about sodium channels. Dr Harouthounian at WashU and his group used lidocaine injection. Lidocaine's a more generalized sodium channel blocker, but some of the newest treatments for treating neuropathic pain. Our NAV specific sodium channel blocker’s trying to match up mechanism to treatment. Not exactly the way that we do with migraine, but still a step forward to not just generally treat but really target different neuronal mechanisms. It's an exciting time.  Dr Jones: So, the pipeline is doing better because we're getting better understanding of disease, and hopefully that pulls in more interest because obviously there are big gaps in caring for patients with pain. And again, thank you, Dr Argoff, for an amazing article. Thank you for joining us and thank you for such a fascinating discussion. I enjoyed the article. I read the article, I learned from our conversation today. So, thank you for joining us to talk about central neuropathic pain. Dr Argoff: Thank you for having me. Dr Jones: Again, we've been speaking with Dr Charles Argoff, author of an article on central neuropathic pain in Continuum 's most recent issue on pain management. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Doctor Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.