[MUSIC] Welcome to Endow Voices, brought to you by the American Association of Endodontists. The show where we are advancing the art and science of endodontics and promoting the highest standards of patient care with today's top experts in the field. Now here's your host, Dr. Marcus D. Johnson. Doc, I really appreciate you for joining us today. You know this is fantastic. Thank you for having me. Yeah, and it is unique experience. It is unique, you know. But you are definitely seen as a thought leader within our field. And it's just a pleasure to be here, A.A.E. 2023, live in Chicago. And your host, Marcus Johnson, and today we have a dynamic guest, Dr. Nikita Ruprel, who all of you have been familiar with and have read the literature and are being thoroughly educated in your endeavors and your studies in pain. And so that's why we really want to bring you on. And we know you had some exciting things to share yesterday with Dr. Hargraves, who I have had on this show before. And really, he enlightened us to the point where I was like, Doc, we love you. But we just want to keep it out of basic level because we have a lot of listeners, undergrad, my mom listens, you know, there's nothing about dentistry. And of course, the endodontist's internationally nationally. So just very light discussion. But before I loop you in, doc, you know, just kind of give us a little bit about your your background and kind of your journey to this point. Yep. Thank you, Marcus, for having me. This is a very unique experience. So I'm like excited to see how this hour goes. So my journey started in India where I was doing a Master's in Neuroscience, moved here to do a PhD. And actually, Dr. Hargraves' lab in under- in pain biology, in Neuroformal College, who's actually studying the effects of cannabinoids as potential analgesics, or peripheral analgesics rather. And while I was doing my PhD, I learned that I could do dentistry on the side as a DDS PhD student. And so I got very interested in the clinical aspect and it tied in very well with the endodontic specialty because we treat pain. Yes, that's, we are the specialist in pain management. Absolutely. So it made a lot of sense to take my basic science research into clinical care. And then as I did dental school, I got interested in the donates and then that's how I got my DDS PhD and residency. I spent a few years doing, I spent one year in Loma Linda as an assistant professor, then moved back to San Antonio for family reasons. And then now I'm the director of the graduate program. And so here I am. Yes, and here you are. And thank you so much for that background. And that's an amazing journey to get to this point. And I think that you kind of highlight a point on the cannabinoids. And we're going to get into that in some of the anti-hyperalgesial, we'll say, and the effects of that. But let's just kind of frame this discussion around just the strategies for pain management. And let's really just put out the information based within the literature as what is the best ways to manage post-operative pain as it relates to endodontic treatment. Yeah, and this is what we covered for majority of our talk yesterday. But for those that missed, we're really trying to, of course, stay away from the opioid prescriptions. And so at least in our clinic, for acute pain management, it's always a sedumine of pen and insets. There's considerable research that supports the use of those. For post-operative pain, for patients that end up having pain greater than six months after endodontic treatment, which is really considered as chronic pain. At that point, at the six-month time point is where we define somebody having chronic pain. And the biggest way to identify what how they're experiencing pain is whether they're experiencing it through peripheral sensitization or central sensitization. If it is peripheral sensitization, our thought process is that they're peripheral inflammatory mediators that are still in the very periapical tissues, despite resolution of the disease, there is no resolution of the most receptive aspect of apical paradigm titles. And the thought process is that there's still inflammatory mediators that are stimulating and activating and sensitizing most receptors. So of course, once drug-com class that we did really used to curb or reduce the levels of inflammatory mediators of these steroids. So typically we don't think of steroids as analgesics. We think of anti-inflammatories because there is significant amount of research that supports as an anti-inflammatory drug, as a drug that reduces swelling, but not so much as an analgesic. However, there is data that supports the effects of steroid on non-immune cells. So there's data that supports that steroids act on epithelial cells, mucus gland cells, and some others. And in fact, classical study by Marshall Devore actually shows that it has direct effect on sensory neurons. And they can inhibit activity of sensory neurons under, experimental condition. So there is more and more data coming out that supports not just the inflammatory effects of steroids, but also the analgesic effects of steroids. And our recommendation in terms of how we prescribe steroids is really based off of Gordon Marshall's work where about 0.07 to 0.09 milligrams were kilograms, which for an average weighted individual would be 7 to 9, sorry, sorry, 4 to 6 milligrams of dexamethasone. Exactly, the 4 to 6. Yeah. And I guess when we're talking about, I guess this is for just a general sense, a medial dose pack, right? Yes. And the 4 milligrams. So when we're discussing that, are we saying that based on the evidence, we have to really wait for six months to really bring that as a adjunct to pain management? Or when can we actually introduce, say if we're if the insets combo and the acetaminophen, using what 500 or 1000 milligrams. And if we're looking at best evidence, 600 milligrams for the insets, after that is ineffective, what is maybe the time range when we introduce the medial dose pack or the cortic steroids? Great question. Actually, you can use it any point. You don't have to wait for the patient to become chronically painful. So yeah, I think as soon as you recognize that the the insets acetaminophen combination is the patients refractory to it, I think you can start with steroids as long as of course the medical history is clear. Of course. Absolutely. I think you don't have to wait. It's just going down, going down your tier of drugs that you want to have in your medicine cabinet. So it's insets acetaminophen first. That doesn't work. Then steroids is, I would say, the most harmless next class of drugs that you could opt for. Okay. And are we at any time introduced? I mean, of course, understanding the patient's history and their risk introducing any sort of opioids at any point along that journey of pain. That's a good question. So there might be patients. Of course, there are multiple other options. You know, after steroids that we could consider. But if we had to prescribe an opioid under extenuating circumstances, then actually the drug abuse database does point towards you the use of tramadol or ultrasound, which is tramadol with acetaminophen. That appears to have the lowest abuse potential amongst all opioids. It does have an abuse potential. It's not clear of that. But compared to the oxycodone and hydrocodone, tramadol appears to have a least abuse potential. In fact, it has lower abuse potential even compared to benzodiazepines. So if the your patient absolutely needed to use, for example, if your patient's already a chronic pain patient has been taking steroids or have been taking patent-like drugs, which are centrally acting, which is the next class of drugs that would do after steroids if they didn't help. But let's say they were already on these medications. And now, you know, they're still a chronic pain patient, then I think a tramadol prescription, again, for a short duration of three to four days. I think would be the next best option. Again, that's after exhausting all the way. After exhausting, right? And because of the low abuse potential. Okay, so I mean, this is very interesting, you know, because as a clinician, and just to clarify, we know you're an academic and researcher educator. And what about your clinical, are you involved in any sort of clinical as well? How many days a week are you? My own practice, you mean? Yeah. Yeah. So I actually practice one day a week in UT, but I also have an independent contractor situation with a private practice, which is a moon lighting arrangement. That's fantastic. Yeah. That's one day a week as well. And you know, it's interesting about that. We love being able to bring on clinicians, researchers, but when you can combine those two worlds and really just bring, I guess, the theory and, you know, apply it to what we do on a day-to-day basis. That's really what we're after. So I love this discussion. And we know you have the science to, you know, support where we're have taken this discussion, but we're really just looking for the clinical applications. And so I guess that brings us to the next question of, well, where do we see the future of analgesics? And I know you mentioned, you know, first, if we were to just go back from
The recommendation, the insets with the acetaminophen, you know, there was a recent poll, it could have been, I think, 2015 of the AB of endodontus, specifically those that were board certified, and the recommended cocktail was pretty much 600 milligrams of the inset and then 500 to 1,000 milligrams of acetaminophen. So I'm glad we established that, that is the best recommendation. Then we can introduce cortical steroids if need to, measure dose pack and maybe after that some sort of opioids. So beyond that, where does the future take and guess what analgesics? - So just to clarify, at least in our clinic, we're not prescribing medral dose pack as routinely because the British medical journal did publish that even a short course of six days can render certain susceptible patients to sepsis and tomboymbolism and fracture like adverse effects. So that a six day time point is really close to what a medral dose pack prescription would be. - Exactly, yeah, it's usually six days. - It's usually four to six milligrams of dexamethasone for about one to three days only. - One to three days. - Really just put it in a circuit, peripherally. But then, extending on the rest of the question, our next step would be for chronic pain patients would be essentially acting drugs, such as gabropentine, even tricyclic and adecrescence. But when you ask about future of endodontics, I think what's really upcoming and is in phase three clinical trials with the company vertex is the VX-548, which is an NAV1.8 inhibitor. It's specific for NAV1.8, which is a TTA resistant sodium channel. And so having a pill just for targeting that inflammatory sodium channel will be groundbreaking. - Yeah, I would because those, I think it's the TTRX, those resistant sodium channels. You know, I was talking without the hard guys about that. And it's interesting to see how we can actually specifically target that. - We'll be right back with more, after a quick word from our sponsor. - The new year is here. An endodontic practice partner is kicking off their third annual root for your Fave T-shirt design contest. This contest gives endodontic residents the power to show off their creativity for a chance to secure funding for their program. Residents, submit your endothemed graphics through March 14th. And encourage your co-residents to do the same to boost your program's chances of earning the grand prize. For contest details, head to EPP's Instagram page named Indo Practice Partners. If you're attending AIE26, be sure to stop by the EPP booth to say hello. They'll also be hosting a special event for endo voices. And between sessions, don't forget to get your free professional photo taken at the headshot lounge, courtesy of EPP, endodontic practice partners, supporting endodontists, empowering practices, and shaping careers. - And now we're back live on the floor at AIE23 in Chicago. So you're definitely taking us along a good path, but I still kind of want to just kind of see where we start to transition into other, I guess, novel endo-gisics, can have an ointment for example. - Absolutely, that's also in the pipeline. In fact, I wouldn't be able to share any data with you because it's not my data, but one of our own faculty, Dr. Vanessa Crepa. She did a clinical trial within our graduate and endodontic clinic using a CBD drug, which is called EpidialX. It's the only FDA approved CBD drug that was approved for epilepsy. But she used it for evaluating postendodonic pain in patients that had preoperative pain of three or more. And again, like I said, I can't share the data with you because it isn't published, but it's promising. It's very promising. In fact, there is already data to support that CBD has shown in animal models at least, significant efficacy in animal models with chemo-therapy, in use in neuropathy and inflammatory conditions. So it's a highly promising drug class that's coming in. I mean, we have four times more cannabinoid receptors in the brain than we have opioid receptors. So its efficacy should be quite high. Of course, what we're trying to do is utilize CBD as a peripheral analgesic, not something that's centrally active. So you avoid all the psychoactive side effects. However, CBD does not seem to have too many psychoactive side effects like the THC component of cannabinoids. So all in all, it has a lot of promise. And we're waiting once the data gets published to actually use it in our clinic. - We're looking forward to that. I mean, I think there's just a lot of energy and excitement about cannabinoids and its effect on no susceptors, but definitely more research. I know you can't disclose too much, but just I guess from a practical sense, is there any sort of application that we can use at this moment? - So like I said, I mean, for off-label use, you can be-- - It's history? - Yes, it's history. - Yeah, it's a big zepidial leg, because we're using it as a drug for the clinical trial. And I believe it's an oil-based-- - Okay, okay. - You know, you just take it orally, oil-based form relation, so because it's FDA approved, you could technically use it. But I would recommend that wait until the data comes out, so you see both the efficacy-- - Enda. - And the side effects - The side effects. - So file. - Right. - And then recommend it for your patients, because the side effects I can tell you are not major at all. But again, based on patients medical history and age and gender and things like that, you might see candidates that will be best suited for it. - And would that be something, once we can actually bring it to market? And of course, evaluate for any sort of side effects. Would that be something that would take place of our recommendation of insets, anesthetia, menophan? - That's a great question. I think, again, a clinical trial that compares those two would have to be done before you make that decision. Both recommendations would likely have very mild side effects, but from an efficacy standpoint, I think a true clinical trial that's randomized, a prospective study, would need to be done comparing it to placebo and sezacidamin offend versus epidial lex or any other CBD combination. So unless that data comes out, it's gonna be hard to answer that. - Yeah, be a little tough. And it's interesting when we talk about the evidence and obviously metanalysis and randomized control trials, that's what we're kind of looking for for best evidence to support what we do day in and day out. But I think this is an interesting discussion because we have to talk about patient safety, but also how do we get the balance of efficacy as well? And just personally speaking, I tend to have, if I were to quantify, 95% of my cases that they do have postoperative pain, it's well managed with just the inset and the seed of benefit of the combination. But I think we were showing that the evidence when it does exist beyond that six month mark and we move to actually removing that tooth, that sometimes that pain is still persistent. - Absolutely. - And so this is kind of, you know, talk about that phenomenon. And when do we bring in the other specialists, maybe the TMJ specialist, the neurologist? - Absolutely. And that was the last slide of our presentation yesterday that don't try to be the one stop shop for pain management. I mean, there are definitely patients that are going to be outside or experiencing pain conditions that are outside of our expertise. And then a proper referral at the right time is prudent. - I think so, the scenario you just pose that once you've extracted the tooth, there's still pain at the site of the extraction socket. That's really describing a processing dental algorithm which accounts for about 1.5% of all patients, where seemingly even after the tooth is extracted, the site from where the extraction happened, where there is no pathology now, still continues to be painful. - Yes. - Which really resembles something like phantom tooth pain. - Exactly. And it's so frustrating as a clinician from standpoint of us really trying to be the specialist and manage their pain. It's extremely discouraging. - Absolutely. And so I think one of the things that we're now starting to think of, dental pain as not just inflammatory, but also neuropathic. So when you extract the tooth, or when you do a root canal, you're actually severing the nerve fibers that are in the periapical tissue. So you're actually causing physical injury to these nerve fibers. So why wouldn't they experience neuropathy? So it makes a lot of sense that there will be a certain percent of the patient population that will experience neuropathic pain. We don't have a true number of that. It appears to be about, you know, to slightly less than 2% of all our patients. It's a little hard to clinically assess if these patients have neuropathic pain or not, because there's the classical signs of neuropathic pain are burning, paying electric shock.
Yeah, let's just shot lancinating pain. One of our patients actually feel that. They just come in with persistent mechanical pain, to chewing or to palpation. So they don't truly fall in the category of neuropathic pain, but in our minds, it's conceivable that some of these patients do undergo neuropathy because of the fact they were severing the fibres. So those patients may have to be treated with drugs that work for neuropathic pain, such as the abependent, like I mentioned earlier. So yeah. - Well, you know, it's interesting that, you know, you're kind of talking about actually what we do from a standpoint of when we're actually instrumenting the canals, severing the, you say like the nerve bundle. And I had a fascinating discussion with the medical doctor, the medical Rikuchi. And so if we really think about patency, just to bring that in, and actually trying to preserve that periapical element and maintain that vitality and that blood supply, maybe then, or at least from his point of thinking, we shouldn't have as much post-op sensitivity inflammatory reaction at the apical region, but that's a discussion for another time. (laughing) - That's the discussion. - That's the discussion. - Yeah. So I mean, so I think this is fascinating because pain is something that we deal with on a day to day basis, even from the standpoint of sinusitis and sinus pain. And I've actually been able to just build up a nice network. So I practice in Manhattan, and I have a role with the ex of just neurologist TMJ specialists, as well as ENTs that I can properly refer to when I feel that the pain is out of my hands in terms of management. But I did say it's a very small percentage. And when we get to that point, if the, we find that the pain can't be managed with, you know, referral to the neurologist or the TMJ specialist, you know, what is our next option after that? - Thank you. - Sorry, when we can't. - Yes, when we find that maybe even they can't assess the real underlying cause of the pain. - So we, so one of the concepts is a top down mechanism of pain where now you've got your central, you know, centers in the brain that get recruited and engaged as part of the pain experience. And so for those patients that have no relief with any of the classically known analgesics, I think behavioral therapies, cognitive behavioral therapies seem to be the next, you know, best route - Right. - To really make that experience less painful. Not to say that the pain is not real. The pain is still real, but sometimes you have to change the synapses, the plasticity that is occurring in the central nervous system through other non-pharmacological methods. And so it might be that those patients would follow that category, but truly I'm not an expert at that. And so I couldn't, you know, say too much about it, but I think that would, if patients are truly refractory to every single analgesic, then I think other non-pharmacological methods would probably need to be applied. I guess I should have probably been a little bit more clear, but thank you for that review. I've had a lot of situations, well not a lot, but some situations where I found that actually the pain was based in a muscular component. - I see. - And so just like with maybe a flex role or muscle relaxing, I was able to actually get pretty good outcomes. And so I find that sometimes it's just kind of based within a, like I said, in a muscle component, when it is that chronic pain, but oftentimes we overlook that element. - Oh, absolutely. Yeah. - So TMD, I think as you pointed out, Don Nick's dwarf and Alan Law's work will point that TMD appears to be one of the primary free disposing factors for post-operative endodonic pain. And so that definitely should be as you're differential, as being the source of the pain, not so much the site of the pain. - Got it. - So TMD management, and I've done flex role for a few of my patients as well, again, not a large population, but still I've done it a few times. And then also a referral to a chronic pain specialist would be a good idea for some of these patients because they can truly diagnose whether it is adonogenic or non-adonogenic pain, which is my a fascial like pain, or even headache like pain, migraines, or trigeminal neuropathy like pain. So yeah, a timely referral to neurology, is a TMD specialist is absolutely within our scope of practice. Sometimes like I said, you can prescribe those medications, but I think once it gets to that point, I think it's best to have that patient be seen by the specialists, then try to manage them in our clinic and struggle with it. - Yeah, 'cause we've all seen the imaging online where it's like 15 root canals in a row, and you're just kind of chasing that phantom pain. And obviously the root canal is not the cause of the problems of non-adonogenic in that case. I don't really wanna bring into this discussion of malignancy, but I guess at some point that can be a factor as well. Well, Dr. Ruprile has really been just a great time just to kind of really frame a conversation around best practices for pain management, post-operative, and what we're supposed to do when we have long term discomfort or pain that lasts beyond six months, and just the effects of canvanoids on, I guess, peripheral so that no-saccepter sensory reactions and what's really what's coming down the pipeline with that new medicine, so. - Absolutely. - Yes, but if you'd like to just maybe kind of just give us a few more words, it's. - Yeah, so I think last words would be, have more than one plan, have more than one medication, your medicine cabinet, and try to stay away from opioids, as we've always said. And there are a lot of alternatives just look out for what's coming next and really look out for the NAB1.8 inhibitor, I think that's gonna be the next best thing. - It sounds like it is, and just to clarify, really watch out for the opioids just because of the abuse potential. - Yeah, but even though it does kind of produce more of a euphoric effect, I do find it's pretty good for patients who quote unquote can't get sleep. - It's not like I can't get you sleep, I need, you know, so that's what I kind of use it for. - I guess they can just say, "Yeah, I'm not gonna talk about that." - Now we're getting into the alternative medicine. Oh wow, well, you know, it's been a pleasure. I really appreciate you taking out the time to enlighten us and you're always a friend of the podcast. - Thank you so much, Mark, 'cause this is really good. - Yes, good conversation. - Hey, before you go, I'd like to give a special thanks to our sponsor. - In the Donut Practice Partners provides beneficial business resources to support and grow each of our endodontic practices. Our mission is to be the trusted service partner for endodontists, their staff and their patients. We will add value to every practice we support and create meaningful financial returns for our doctor owners. - Thank you for listening to this episode of Endow Voices. Don't forget to subscribe so you can catch all of our upcoming episodes covering the hottest topics in endodontics. As always, we welcome your questions, comments, and ideas for future show topics and guests. Email us at
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