Dr. Venable: What do you think are some of the best practices in managing pain for veterinary, especially oncology patients? And how would you say that compares to general pain management?
Dr. Lascelles: I think best practices revolve around a careful assessment of the cancer patient for all those sources of pain. Remembering not to forget that just because a treatment is aimed at curing cancer, we can't just ignore the side effects of that treatment.
Dr. Venable: Welcome to the Veterinary Cancer Pioneers Podcast, the show where we delve into the groundbreaking work of veterinary professionals who are dedicated to advancing the field of veterinary oncology. I'm your host, Dr. Rachel Venable, and I'm thrilled to embark on this journey with you.
Dr. Venable: Hello and welcome to the Veterinary Cancer Pioneers podcast. I'm your host, Dr. Rachel Venable, and today I'm so excited we are going to be talking with Dr. Duncan Lascelles. And we're going to go into pain. And how not only that can affect our patients and their quality of life, but also learn some really interesting research and how it could have a greater effect on cancer in general.
Dr. Venable: So we're going to dive into all of this today. But first, let me introduce Dr. Lascelles. He is a leading expert in veterinary surgery and pain management. He graduated with honors from the University of Bristol Veterinary Program and completed a PhD in preemptive analgesia. His impressive career includes a surgical residency at the University of Cambridge, a fellowship in oncology surgery at Colorado State, and postdoctoral research in feline pain at the University of Florida.
Dr. Venable: Currently, Dr. Lascelles is a Distinguished Professor, Professor of Musculoskeletal Health and Translational Pain and Research and Surgery at North Carolina State University, and directs the Comparative Pain Research and Education Center as a board-certified Small Animal surgeon. He has dedicated his research to developing methods to measure and understand pain in pets with naturally occurring diseases, and aims to enhance pain control and companion animals, and support analgesic development in human medicine. Dr. Lascelles has authored over 250 peer-reviewed research papers and is an active member of several prestigious pain research organizations. So, so much very impressive career, lots of education. Thank you, Dr. Lascelles, so much for being on with us today.
Dr. Lascelles: Well, please call me Duncan, and thank you, Rachel, for having me. It's an absolute honor to be asked to be on your podcast.
Dr. Venable: Oh, well, the honor is all ours for sure. And I always like to ask people when we start just, you know, if you can share a little bit about your background and how you got to become a veterinarian and then also specialize in pain, you know, you have a lot of education. So what got you into the pain side?
Dr. Lascelles: Sure. Yeah. Well, starting with being a veterinarian, I've always wanted to be a veterinarian. And I honestly can't remember when I first decided that, you know, that's now lost. Actually, I always wanted to be a veterinarian. Go back to Africa, where I was born and treat wild animals. So that that hasn't quite panned out. But I have a fascinating life. And it is, all around pain. I try and understand the clinical impact of pain and the mechanisms that are driving that pain, and that interest in pain started because way back, you know, when I was a small kid, I was fascinated by memory. And then once I got into the memory curriculum, I was taught by a physiologist where I'd learned that pain and memory shared many of the same mechanisms. And then later in the back course, once I got into the clinical years, I learned that pain was such an underserved area. We really didn't know how to assess it or treat it well. And so everything came together for me. You know, he was my excuse if you like to study memory by studying pain. And there was a very good reason for doing that. And then I think the final piece of this is that my father suffered chronic pain. And, you know, I would say he died from it. Now, he didn't die from pain. He died of a heart attack. But he the person he was died because of chronic pain. I mean, you know, my father, the fun-loving, life-loving person that we knew had gone, had died, had disappeared because of that chronic pain. And so, I think, you know, that was a moment where, I really understood the negative impact of pain on people. And I think back attention on the animals that we serve.
Dr. Venable: Well, I'm so sorry to hear about your father. That that sounds really tough and certainly makes sense how it made such an impression.
Dr. Lascelles: It did. It really did. Yes.
Dr. Venable: And some of the things you mentioned, memory and pain. I never really thought about that before, but it does make sense. You know, you touch a hot pan as a child, you learn really quick. You remember not to do it again. So that is interesting how those two go together and you kind of to to go back to our veterinary patients.
Dr. Venable: What do you think are some of the best practices in managing pain for veterinary, especially oncology patients? And how would you say that compares to general pain management?
Dr. Lascelles: Yeah. I think I have to say that for the the cancer patient, it's a little bit more complicated because I think we have to remember for the cancer patient that pain can come from the cancer itself. Many cancers as we all know, can be associated with pain. But pain can also come from the treatments that we use for those cancers, whether it's surgery, chemotherapy, radiation therapy. And then finally, this is often forgotten. Pain can be present in our cancer patients because of other diseases in disc disease, and osteoarthritis. And so I think best practices revolve around a careful assessment of the cancer patient for all those sources of pain, and remembering not to forget that just because a treatment is aimed at curing cancer, we can't just ignore the side effects of that treatment, particularly when they're pain.
I think another best practice is a multimodal approach, and that's particularly relevant if you have multiple sources of pain in the individual patient, and then regular reassessment and adaptation of therapeutic approaches as appropriate. So I think the approach to the pain in the cancer patient is very similar to other patients. It's just I think we are juggling more. And I have to say with that overlay of the emotive issue of cancer.
Dr. Venable: You're right, there can be so much going on with our patients. You know, you've got the cancer and the side effects and just trying to battle that. And so and it makes sense because I do feel like most of our patients, they're old. And so they usually do have arthritis. And like you said back disease all kinds of things. So that's great I like that. And what would you say are your go to resources when you're looking at cancer pain management? What would you recommend to help guide practitioners?
Dr. Lascelles: That's a great question, Rachel. I it's a great question because information is so easy to come by these days that we can easily be overwhelmed and not really know where to go. If anyone listening is wanting to kind of explore the area of cancer pain management and the impact of pain in cancer patients, maybe a couple of resources. One would be Withrow & MacEwen’s Small Animal Clinical Oncology. Chapter 16 to be specific for full disclosure, I was one of the coauthors on that with Timothy Fan, and Mike Nolan. But I think that's actually, you know, even though I was involved with that, I think that's a pretty good resource. It covers all aspects of pain in the cancer patient.
And then I would also recommend the 2022 pain management guidelines. Now the focus of the information and the discussions around persistent pain really mainly pertains to osteoarthritis. But the same principles apply, and they're great resources that can be applied to the cancer patient. So those are the two places I would start and then go out from there.
Dr. Venable: Yeah. Those are great ones. I certainly the Withrow & MacEwen’s I have multiple versions behind me there today.
Dr. Lascelles: So do I. Yes.
Dr. Venable: Right. I believe so young college is that is our go to.
Dr. Lascelles: But so so many fabulous contributors to to those various editions.
Dr. Venable: Yeah right. Yes it is a fantastic textbook. I always recommend that to vets. You know, if they're not an oncologist, but they like cancer and that kind of thing. I'm always like, go to that book. In fact, when I was a vet student, Dr. Henry was my main professor, and she told me so. I told her I was interested in oncology and she was like, well, read this textbook. It was Withrow & MacEwan’s. She's like, you can read this whole book and you still like oncology? Then? I think you should. Specialists. Oh, so yeah, she got me reading the whole book. So I've been reading the whole book for several fabulous. So what steps can veterinary clinics take to help improve their current pain management protocols?
Dr. Lascelles: Yeah, I think when it pertains to the cancer patient, what I see when I go into practices is the fitness rings are actually doing a great job of utilizing current information on pain management and applying it to cancer patients. I think when it comes to cancer patients specifically, my main suggestions are recommendations would be remember, cancer can be associated with pain. But as we've said already, the treatment for cancer can be associated with pain, and pain may be present in those patients for non-cancer conditions. And so that's just really important to keep coming back to and keep remembering as you move into the management of pain in the cancer patient, always be asking, what is the evidence around a therapy for pain management? And I say that because, you know, just because we see therapies being used, we mustn't necessarily assume there's robust evidence of efficacy. Essentially, we mustn't assume that they do work. I think in veterinary medicine we try and do our best and we may reach for therapeutics, hoping we can improve the situation. But therapeutics where there isn't necessarily a lot of evidence. And I think an obvious example of that is gabapentin. I mean, gabapentin is used like water and there's very little evidence that it provides any beneficial effect. I'm not saying it doesn't, but I think, you know, as we use that, we've just got to remember, okay, let's just not assume that that's going to be effective and going to provide the pain relief we need.
The next recommendation would be think about assessment of that patient and reassessment as you instigate therapies. And then finally coming back to something we mentioned earlier. Remember the importance of pain. Persistent pain can kill the animal. It can kill who the animal is. And I think we also have to acknowledge and admit that sometimes managing pain may be more important than chasing a cure for the cancer. And I think you know that may be a difficult thing to say on this podcast, or difficult thing for people to, to hear and internalize. The patient cares about how they feel. We may care about cancer and curing cancer, but in the road to Jewel, in the road to achieving that, we have to think about how the patient feels. And I think pain and the management of pain is an important part of that.
Dr. Venable: And it's a good point. And you're right, we do often focus on treatment and just, you know, certainly in people, you know, other people I've known in my life had to be on chemo and kind of harder regimes. It really feels like they're just pushing them to get, you know, it's like, if we can get past this. But you're right. You do really have to remember quality of life, because how much are we helping them if they're miserable the whole time? And what if they don't make it all the way through? So it's tough.
And your comments about gabapentin to go back to that, because I am I will admit I am someone who prescribes a lot of gabapentin. Do you recommend them? Like with gabapentin? Just making sure like the animal is getting better. Is that kind of what you're saying? Like, I know you're saying there's not a ton of data, but if you prescribe it, just making sure like your point number two of that, you know, that they are like reassessing that it's working.
Dr. Lascelles: Yeah, absolutely. Yes. And I think also just remembering well why are we prescribing gabapentin. You know, is it because we're afraid of say nonsteroidal anti-inflammatory. You know, and then you have to think, you ask yourself is that fear justified in this particular patient or is it just a blanket fear. And if we are using gabapentin, let's assess whether it's actually having the effect we hope it will have.
And I don't doubt that gabapentin is beneficial in some circumstances, but I think taking that to a number of levels away from, you know, it may be beneficial to assuming it's beneficial across all sorts of different pain scenarios. That's what I think we have to be careful about avoiding.
Dr. Venable: Right. Yeah. No. Assuming is always bad. Right? I won't go through the acronym, but we all know that it's it's we're not supposed to assume. So you right. Definitely need to reassess and think so kind of along that, what do you think are some misconceptions about pain management in veterinary oncology?
Dr. Lascelles: You know, I think I think the biggest misconception, at least the one that's on my mind the moment, is the idea of downgrading the importance of pain and we've touched on this a few times already. But, you know, pain is one aspect that defines quality of life. I believe animals pretty much live in the moment. And so how they're feeling at that time, that is their life. And so again, I think, you know, as we manage cancer, we have to be cognizant of the presence of pain and cognizant of the quality of life of that individual. But I'd also maybe extend the answer a little bit into something which I'm really interested in, which is that pain is, in my mind, not just a byproduct of cancer and other diseases, but pain. The presence of pain may actually influence the progression of cancer. And I think maybe, you know. So that goes back to your question about a misconception. You know, pain is seen as a byproduct, as a side effect, as something that needs to be managed. I mean, if you think back to Withrow and MacEwen’s and Chapter 16 is supportive care, which suggests, okay, as a result of cancer, you've got these other things that you need to manage, but pain itself may actually influence cancer progression.
Dr. Venable: Yeah, that's a really interesting thought. And you know, Dr. Nicola Mason, when she was on here before, had mentioned that you were doing really interesting research on how pain can influence cancer progression. So can you kind of dive into that some more. Can you explain that a little bit?
Dr. Lascelles: Sure. Yeah. Nikki's great and very, very fond of Dr. Nikki Mason. Yeah. So this concept is that pain per se the presence of pain may enhance cancer progression. And I'll, I'll say this a few times in different ways because it is a new concept. So we're not talking about, you know, if cancer is worse is more aggressive. It's associated with more pain. Talking about the concept that just the presence of pain could influence the progression of cancer and essentially influence ultimate survival. And I think one way into thinking about this revolves around sensory nerves and what sensory nerves do. So classically, we think of sensory nerves as being out in the environment and sensing the local environment. You know? And when it comes to pain, they tell us when there's a noxious stimulus or something bad happening in the environment. So we think of them as sensing. We think of all the information going into the central nervous system.
What we forget is that we know and have known for decades that sensory nerves actually contribute to the local environment. So when a sensory nerve is activated, it releases, for example, vasoactive neurotransmitters into the local environment. And that's why when you, you know, say you cut yourself or damaged yourself, you see what's called a flare, this red flare develop. It's actually sensory nerves being active and spitting out these veins of active substances into the local environment. So active sensory nerves can influence the local environment. Then you can start to build on that through evidence that is in the literature now that sensory nerves certainly locally are involved in enhancing cancer progression locally. And then there are other data that indicate that the presence of pain itself in one part of the body can actually influence progression of cancer in another part of the body.
Dr. Venable: That's really fascinating. So, sensory nerves and then progressing of cancer just from pain. So do we think that and maybe you'll go into this, but do you think it upregulates receptor, like how do we know how we think that pathway all happens?
Dr. Lascelles: I don't think we know. I think if you look through the literature, I think you could explain this. And they're not mutually exclusive. You could explain this by looking at three different aspects. One would be, for example, that the presence of pain has some sort of a depressive or adverse effect on immune function, and that then allows cancer to progress more easily. Another way of explaining this, or thinking about it would be to say, okay, the effects are all local. So we talked about sensory nerves, and you can imagine an osteosarcoma that is innervated when those sensory nerves are activated. As the animal walks, they actually spit out these neuro, these vaso active neuropeptides into the local environment. And they somehow could potentiate the progression of that local cancer.
Also, we've known for a long time about perineural invasion. And, you know, that is the mechanism by which cancer cells actually, invade, get under the neural sheets of nerves and contract along nerves. And it's thought that that is a gateway to hematologous in a spread. And then I think the third kind of concept to think about and this is not very well defined, is the idea that ligands that are involved in producing pain.
So think back to that. Osteosarcoma, the very substances that are involved in producing pain, those ligands could actually be promoting cancer itself locally, but also systemically. You know, you can imagine something like nerve growth factor that we know is produced, not just sarcoma gets into the bloodstream and potentiate metastasis in other parts of the body. And then another kind of widespread, concept here would be the idea that if this pain is present, the whole nervous system becomes upregulated. And it does. We've all heard of central sensitization. And so then nerves, sensory nerves in other parts of the body are more active, are more twitchy. And if there's metastasis in another part of the body, you can imagine then that there's an interaction between those metastatic tumor cells and sensory nerves in a way that can promote progression of metastasis. Is now that to emphasize, you know, that's not all based on data, I'm putting together pieces of real evidence, but also presenting some concepts there as well, because there's no doubt if you start to look through the literature, there's no doubt that pain in some way is able to promote the progression of cancer.
Dr. Venable: And that's really interesting. And can you describe some of those studies that have shown how pain can influence that distant cancer progression?
Dr. Lascelles: Sure. Yeah. The ones that first came to my attention, and I think actually these studies, about half a dozen of them by Paige and coworkers in the late 1980s, early 1990s, they were really the first studies. They caught my attention. And what those investigators clearly showed was that in rats that underwent laparotomy, had surgical pain, the retention of cancer cells in the lungs was increased, and that retention of cancer cells in the lungs was mitigated by the use of perioperative analgesics. And it didn't appear to be simply an effect of the analgesics themselves. They looked at morphine, they looked at local anesthetics because they used the appropriate control groups. Animals that were just anesthetized had the cancer cells injected and then had the analgesics. So with all the appropriate control groups and so on, I think there was very clear evidence from those studies that there was something about pain, perioperative pain that was influencing the retention of these cancer cells in the lungs.
So those are the first studies that influenced me. And then much more recently, working with Dr. Mike Nolan, a friend and colleague here at NC State, and work done by Connie Manasas, who is a shared graduate student. We produced more evidence of that relationship between pain and cancer progression. And so Mike had developed a model of radiation associated pain of the tongue, so or rack for short. So he'd taken these, these little mice, and irradiated the tongue. And that radiation associated mucositis is associated with pain. And he demonstrated that. So this model of radiation associated pain. In that model, what we did was at the time of maximal wrap, some maximal radiation associated pain, we injected 41 cells into bulb C mice and again with the appropriate control groups and so on. What we found was that the time to metastasis was shorter and metastatic burn was greater in mice that had radiation associated pain. So again, just to sort of think about it visually, you've got this radiation associated pain in one part of the body. We're injecting these 41 cells into a tail vein. They float around, they go to the lungs. If there is rat presence or radiation associated pain present, the metastatic burden is greater in those mice. Okay. So that's interesting. And I wasn't we didn't hold totally true for other cell lines. It didn't hold true for B16, F10 cell line. It did hold true for a mock two cell line. So there's some differences there. But maybe most interestingly, the lung tumor growth was normalized when RAF radiation associated pain was reduced by treatment with never since the very toxin is this toxin that knocks out or knocks back a large proportion of the sensory nerves. So essentially what we showed was that the phenomenon of pain induced enhanced cancer progression was mitigated, was taken away. If we knocked back out of play a large proportion of the sensory nerve. So again, I think establishing this link between pain or at least sensory nerves and metastatic growth of cancer cells, that was a lot of information. I'm sorry.
Dr. Venable: It's all very interesting information. And, you know, mouse data, I mean that's really where we've got to start, right? Most of the time. But it doesn't always translate into certainly not people but not always animal, you know, like bigger animals like dogs and cats. So is there evidence that pain affects cancer development in dogs?
Dr. Lascelles: Oh my goodness, I'm glad you asked that. Because it is a really important question. And I think going back a number of years, what I had seen with my interest in surgical oncology, was a shift from a time when think about osteosarcoma in a dog and we're talking about limb amputation. And most people would have agreed that survival was still pretty poor.
They had to go through this amputation, and they're going to die a short one afterwards. And then later on in my career, I was seeing amputations performed, dogs recovering very well from those amputations and actually living longer than the standard median survival in textbooks. And I think the difference from my perspective was pain management. And so let me talk about another study, again, done with with Mike Nolan to credit him for leading this one where we looked at the effect of procedural pain on survival in dogs with limba osteosarcoma.
So we took a cohort of dogs that had been amputated for limba osteosarcoma. Now, this was a retrospective study across two institutions, NC State and Colorado State University. We didn't have content assessments of pain, but what we did have was a surrogate to measure the intensity of perioperative analgesia provision. We looked at this in a number of ways, but the simplest way we looked at it was we said, okay, let's define a group of dogs that have a low level of perioperative pain management and a group of dogs that have a high-level perioperative pain management.
So we defined low level as those dogs didn't get a nonsteroidal anti-inflammatory either pre intra or post operatively, and no local anesthetic use or a line block at best. Then the other group was, we said, okay, dogs have to have a nonsteroidal both before covering and after the surgery, and a local anesthetic catheter that's one of those, like soaker catheters, is put into the wound and you can still local anesthetic, every six hours or so for several days. So that was the high good coverage for the nonsteroidal and solid coverage for the local anesthetic plus or minus any other local anesthetic use. And when we looked at the effect of low versus high provision of perioperative pain management, we found a significant difference in overall survival, the high level of perioperative pain management resulting in a survival almost 100 or days longer than the low level.
Dr. Lascelles: So a very significant separation of those groups. So to me, I mean, I'm fascinated by the mouse data, but this is really exciting because this is meaningful. This is the type of patients that we deal with that we care about. And I think very solid evidence suggesting that there is something about pain here, procedural pain associated with amputation that is affecting ultimate survival.
Dr. Venable: Yeah. Wow. So let me just make sure I'm getting this right. So dogs with osteosarcoma getting an amputation. If you found that they've got more aggressive pain management perioperative and sounds like afterwards too. So like in said soaker catheter, they live longer. So why do you think that is.
Dr. Lascelles: Yeah. Again I have to admit I don't know. But I'm going to come back to kind of the concepts. And so, you know, one reason could be that, the presence of perioperative pain has a negative, deleterious effect on the immune system, and the immune system is just not as good, to dealing with the metastatic disease which we know is present at the time of amputation, in dogs with osteosarcoma. Or it could be something to do. What's happening locally that, you know, pains state there are going to be local ligands that drive pain, whether that's calcitonin gene related peptide substance, p nerve growth factor, and if we decrease pain, there are going to be less of those ligands and those ligands which may also promote cancer. Then I'm not going to get into the systemic circulation. And then the final area would be, well, maybe by managing pain, paradoxically, by managing it well, we're decreasing the chances of getting into this sensitized state where nerves throughout the body have heightened activity, heightened awareness and potentially could play an active role in the progression of cancer at other sites in the body.
Dr. Venable: Yeah. What and what do you think about just owner perception of quality of life? Do you think that played a role like if the dogs didn't act as painful? That's the other reason why the owners maybe went longer. Was there any way to to factor that in with that study?
Dr. Lascelles: That's a good question. So I'll be honest. I think that's something that needs to be revisited in a prospective study to confirm these findings. You try and confirm these findings. But I think also just thinking about the median survival times you're talking, I forget the exact figures, about 250, 260 days in the low-level group and 100 days later in the high-level group.
So we're not talking about how these patients were in the immediate days, weeks post operatively. Making a difference to ultimate survival is something that's having a longer-term effect, other than just, say, how they're recovering from that amputation. But these are important things to think about as we move forward is, you know, let's not make assumptions. Let's keep asking questions about what is actually driving the differences that we see.
Dr. Venable: Are also makes me wonder about some of the studies where, you know, it's looking at osteosarcoma dogs treated with amputation and chemotherapy, and their studies looking at the same chemo drugs, you know, like carboplatin or things. But the survival is not quite the same. And it almost makes me wonder was pain management? Could that be some of the difference between why some studies you know, Carbo just performed a lot better versus that another study.
It didn't, you know, I mean, I'm sure there's lots of factors, but now it's just making me wonder, like, oh, what if those dogs didn't have good pain management? Like what? You know, so it's just so many different levels, so many things happening to think about.
Dr. Lascelles: Right? Yeah. And I think, you know, as we do more of these studies, we observe more. We learn more, and then we can test more theories in subsequent studies. And it reminds me of yet another study that myself and Mike Nolan were involved with. And this one is very much run by Mike. He wants to look at stereotactic radiation therapy versus conventional and a couple of different doses of stereotactic radiation therapy. We added on looking at, baseline pain severity in those patients. And when we looked at the results, there were some no-brainers in terms of results. We know for dog started radiation therapy and chemotherapy for osteocytes. These were these were dogs with osteosarcoma. Again, if they started radiation therapy and chemotherapy that had metastasis, they didn't live as long. So that's why of course, the tactic radiation therapy was associated with better survival than conventional radiation. And a larger dose of stereotactic radiation therapy was associated with better survival. But interestingly, both in univariate and then again in multivariate analysis, baseline pain score affected survival with higher pain scores, leading to shorter survival. Now there's a situation where I think, you know, one of the first questions one would ask is, well, was that because the disease was more aggressive or worse at the start in those patients? So I think that, you know, these are things that do need to be revisited. But again, it does add to this body-growing evidence that there is some sort of negative effect to pain, pain per se on cancer progression.
And I just want to say I'm talking a lot, but I just want to touch on one other fascinating study that was published in Nature a few years ago. And it was all about gliomas in people, so nasty brain tumor in people. And I don't remember all the details, but what I do remember, was that these gliomas formed synaptic and electrical connections with neurons in the brain. And if the neurons in the brain were active, that enhanced the development of these gliomas. And so there's a there's a crazy to me, it's a crazy example of a cancer cell. You know, having a connection with a neuron and then that neuron to affect its own survival and development.
Dr. Venable: Yeah. That is wild to think about. And so I guess part of the next question with all of this is how important is early pain intervention in the treatment, especially for oncology patients. What indications should vets look for?
Dr. Lascelles: I think, you know, if we believe that pain has negative consequences on cancer treatment outcomes, then the follow-up question should be, well, what is the optimal time to intervene? We honestly don't know. And but I am reminded about the work in my PhD that was looking at surgical pain and central sensitization. And I found and others have found the same thing since that the earlier we intervene, the future is better. You know, if we prevent signals from going into the system, we can improve outcome later on. And I suspect as this field develops, I suspect we will conclude that early treatment of cancer pain has a greater beneficial effect on cancer treatment outcomes than later treatment of pain. At this stage, I would, propose that early treatment is better.
Dr. Venable: Right. Not waiting until they're in a lot of pain, but just starting things like early on. So that makes sense. So how do you think effective pain management correlates with client satisfaction? And just then sticking with the protocol or just the plan for their pet treatment?
Dr. Lascelles: That's a really good question. So I think effective pain management is important for client satisfaction. My experience as a client is very much appreciated clinicians that care about how their patients feel, including comfort. And so when you start to acknowledge that, I think you have a a greater connection with clients. But I think education is needed. I don't think owners always know what pain is. I think for many owners, pain means vocalization, screaming, writhing. You know, they think of these very dramatic scenarios. And so I think we need to educate owners as to what the signs of pain may be. Now, owners know what they're seeing. They just need to be educated, that what they're seeing may be associated with pain. At the same time, I think we need to educate ourselves that there are many signs of pain that sometimes we overlook, particularly in the quest to cure cancer. So I think education is really important. And acknowledging to owners that we care about pain and comfort and then I think you have a much stronger team, you that that the treatment team and owners, a much stronger team to get through the course of treatments that are needed.
Dr. Venable: Yeah, and I agree, I think owners like when you talk about, you know, managing their pain or, you know, different ways, different modalities to do it. But I also agree that a lot of them really don't understand what pain looks like in animals. And I think too, because animals will often hide it. You know, it's rare that they truly vocalize and you know, they can't have a chat about how they feel like a person could. So I totally agree. It is really hard for people, and I think education is a huge part of it. And so, you know, as we've been talking, so cancer causes pain and cancer treatment, you know, can lead to pain. And and we're also now think, you know, from what you're saying potentially the presence of pain per se can even, you know, have a role in cancer progression. So how do you recommend that we really detect this level of pain? You know, what should we do to treat it anything different. Would you do anything different with cancer patients? What kind of how are you now with all this information and research you're doing? How are you approaching these guys?
Dr. Lascelles: Yeah. Great. So, you know, we acknowledge that cancer can cause pain. Our treatments for cancer cause pain and further acknowledge that the presence of pain can have an impact on the progression of cancer. Then we have to, we have to take management of pain seriously. And that's honestly, Rachel, where we need a lot more work. So the the pain management field has developed methods to assess pain and some methods to assess cancer pain have been developed. But we need more. We need validated assessment methods across the different types of cancer pain that can measure the effect of cancer pain in different parts of the body. And these are the validated assessment methods I'm talking about essentially client-reported outcome measures or client questionnaires owner questionnaires. But they can also be clinician questionnaires as well. So capturing what we can all see, the behavioral indices of pain on paper through targeted and valid questions. And once we have validated assessment tools, then we'll be able to make headway in understanding what are the best approaches to treat cancer pain.
At the moment, the treatment of cancer pain is pretty much empirical. We say, okay, these therapeutics, these non-drug therapies work in other pain conditions. We've got some evidence for that. Let's try them on our cancer patients. It's not all doom and gloom making everyone and a number of teams are making progress around cancer pain assessment and understanding what most effectively manages cancer pain. But we need a lot more work in this area for sure.
Dr. Venable: And what are some trends or new technology in pain assessment do you think oncologists should be aware of?
Dr. Lascelles: Yeah, I think the one that leaps to mind is leveraging video and artificial intelligence. So I mentioned earlier that cancer pain is manifested through behavioral change. And this as subtle as those may be. And it's difficult to recognize as we make progress, we can train computers to do that process more quickly, possibly more consistently as well. And so that's what I mean by leveraging AI there. We, we basically take what we know, train a computer algorithm to do it more consistently, to do it faster.
Beyond that, potentially, you know, there's a very exciting future in what you might call a black box approach, where you feed information to a computer and ask it to parse out the information into different groups. And and through those processes, we may actually advance the measurement of pain into areas that we didn't even know were possible. It's like, you know, everyone answering that question is going to talk about AI, but it is going to make an important impact to the field of pain assessment, for sure.
Dr. Venable: Right? I hadn't thought about it in that way, but that is really interesting. And, you know, one thing, just kind of thinking of some drugs that I just want to ask you briefly, you know, you mentioned in that study with Mike Nolan, with the mice and the rap, you know, when when you gave them the drugs that I can't remember how you said it, that dead in the sense or is that something commercially available or veterinary or is that still on the research stages.
Dr. Lascelles: Yeah. So we were using that drug, and it's called resiniferatoxin (RTX). It's basically capsaicin on steroids. It's a very, very powerful TRPV1 agonist. So it stimulates, it overstimulate sensory nerves overstimulate them to the point where they burn out and even die back. And so we were using that as a tool. I think there is a lot of interest, though in TRPV1 agonists, things like capsaicin, applied locally or regionally to knock back the sensory nerves so that one pain is decreased. But also then, you know, you don't have those deleterious effects of pain in those cancer patients. So I think there is there is certainly interest in that group of drugs for sure.
Dr. Venable: But it's not something you can really buy or do you know. Is that so research level?
Dr. Lascelles: I'd have to say it's pretty much yes. It is really is research level. Yes.
Dr. Venable: Yes. Okay.
Dr. Lascelles: Just there's always there's always a way of getting hold of something. But no it's research level. Yes.
Dr. Venable: Right. Okay. All right. Perfect. And then one other drug that I know, I get asked all the time, all veterinarians. Librela, you know, those new monoclonal drugs, what are your thoughts on that? And just, you know, cancer pain management or just pain management, do you use that or what would you recommend for veterinarians?
Dr. Lascelles: Yeah. So the Librela, which is bedinvetmab is the first anti-nerve growth factor monoclonal antibody approved for use in dogs and frunevetmab or its trade name Solensia is the first anti-NGF monoclonal antibody approved for use in cats. They are approved for osteoarthritis pain. And I think there's very strong evidence around their utility for osteoarthritis pain. That said, and I think I've mentioned a couple of times nerve growth factor is known to have a role in cancer progression for a number of cancers. And nerve growth factor can drive pain. And so that may actually be dual utility here of an anti-NGF approach for certain cancers, possibly osteosarcoma, possibly other cancers. So very exciting thoughts. Again we just need to define whether there is utility and what that utility is because those tools are available. I know a number of oncologists are exploring their use in cancer pain conditions. So looking forward to some information in that area.
Dr. Venable: Yeah, I know that is really interesting. And yeah, I get a lot of questions and different stories from that. So I'm just since you're the pain expert, was really curious what what your thought was. And Dr. Lascelles, it sounds like you are doing a lot of exciting things in your lab. All this different research. It's really unique, at least to me. I haven't really thought about pain in this way. So what are some other promising projects that you're doing in your lab?
Dr. Lascelles: Yeah, well, I, I certainly enjoy what I'm doing. I think three main areas that we're focusing on at the moment. One is looking at how the microbiome and leakiness of the gut may influence the progression of osteoarthritis and osteoarthritis pain, and that work is NIH-funded in collaboration with Dr. Amanda Nelson at UNC. She's doing the two-legged animals, humans. I'm doing the dogs.
And then another NIH-funded project is one where I've teamed up with Dr. Santosh Mishra, and we're looking to understand the Aretemin GFRalpha3 signaling system and its role in pain. Now, some of you listeners may put up when I say Artemin, because Artemin has been known for a long time to be involved in the progression of pancreatic cancer, it's a neurotrophic factor known to be a driver of pain, but also independently known to be involved in pancreatic cancer progression. So that's kind of nice work because it's bringing together my raw pain interest as well as my interest in cancer management.
And then finally, I have to mention wonderful collaboration with a project that's led by Dr. Mike Nolan. Dr. Santosh Mishra and myself are collaborating Mike, and he's looking to understand the mechanisms of radiation-associated pain, something which we all know is difficult to manage. I know it goes away after a few weeks, but it's really difficult to manage. And so he's making great headway in understanding the mechanisms, the unique mechanisms that drive radiation associated pain.
Dr. Venable: Oh yeah, those all sound like fascinating studies. I love the whole microbiome that is just really opened up into a whole new area. And yeah, and if we could get a better understanding too on radiation pain, you know, just, you know, this could ultimately find ways to help prevent it. Right.
Dr. Lascelles: That's right.
Dr. Venable: That's sort of what I'm thinking about. And I'm sure that's where Dr. Nolan's interested to go I would assume, but that's all sounds really great. Well, we'll certainly have to keep a close eye on your lab. And just thinking about research, what advice would you give that students interested in research or just veterinarians in general?
Dr. Lascelles: Yeah. So from my perspective, research is a wonderful way of helping many animals beyond just the one in front of you. And I'm and I'm not downgrading belittling the, you know, working on an individual animal, one pet at a time. That's desperately important. But research is just another part of the jigsaw. And through research, you can potentially help many animals. So I think that's one of the things that draws me to it. And anyone wanting to get into the area, I would say just start talking to people. I talk to lots of people, develop a passion, understand what the problems are, and even if you don't know what the solution is, aim to find a solution. It can be extremely rewarding.
Dr. Venable: I love that that's perfect. And along with that, what would you say is the most rewarding part of your career?
Dr. Lascelles: Oh, I think it's seen my research actually make a difference in practice. You know, first and foremost, I'm a veterinarian, I love animals, I want to improve our ability to manage those animals and optimize their quality of life. And so, you know, when I see my research make even a small difference in practice, that is really the most rewarding part of my career.
Dr. Venable: You know, this has been an awesome conversation. And as we're wrapping up, just, you know, a question I always like to ask everybody, who else would you recommend that you think would be a good fit for this podcast?
Dr. Lascelles: Wow. All right. We're from the pain topic. Then I would say couple of names that jump to mind would be Patton Mante and Brian Schmidt. So Patton Mante is a basic pain researcher who really he didn't invent, but he really gave a kickstart to the cancer pain research field. So he would be a great person to have on your podcast, Brian Schmidt is an oral surgeon. Human, oral. He's human. He treats humans. He's a he's a surgeon for humans. About oral head and neck cancer. And he's done a lot of research into the mechanisms of head and neck cancer pain, and could also speak on the effect of pain per se on cancer progression. So those would be a couple of pain individuals. I think one thing worth mentioning is I think it's always important to listen to stakeholders. And so I would also suggest owners of animals who have suffered cancer or suffered cancer pain, you know, maybe even have one as a group. What were their experiences? What were their thoughts? Because I think, you know, we veterinarians can live in our little bubbles and talk to each other. But we do need to pay attention to the important stakeholders, the owners of the pets that we're treating.
Dr. Venable: Yeah, I think that's a great idea. And we do often forget about that element too. So I think that's great. And well, Dr. Lascelles, thank you so much. This has been such a fascinating conversation, and I know our listeners are going to love it. I learned a lot. So thank you so much.
Dr. Lascelles: Well, thank you very much, Rachel, for having me. It was an honor, and I enjoyed talking to you.
Dr. Venable: Well, that's it for this episode of the Veterinary Cancer Pioneers podcast. If you enjoyed this episode and gained valuable insight, we would be so grateful if you could share our podcast with your friends and colleagues. And it would be even more wonderful if you want to give us a five-star rating, positive review, or any kind of feedback on Apple Podcasts or wherever you listen. The Veterinary Cancer Pioneers Podcast is presented to you by ImpriMed.