[00:00:05] Speaker A: Welcome to All Cats Considered, a new podcast from the American Association of Feline Practitioners, where we interview professionals from across the veterinary world and take deep dives into the latest evidence based research, development studies and guidelines that improve feline health and well being. My name is Dr. Kira Ramdis, President of the AAFP, and I'm proud to introduce this new podcast.
We are the home for veterinary professionals seeking to improve the care of cats through high standards of practice, continuing education and evidence based medicine. In each podcast you will hear interviews from a variety of experts throughout our field covering a wide range of topics and recent developments in the practice of feline health, sharing the key points you need to know to improve your patient's care. Let's dive in and take a listen with this week's experts.
[00:01:00] Speaker B: Well, I'm excited to be here with Dr. Duncan La Salles from North Carolina State University, who doesn't need really any introduction to all feline friendly people, feline people at all. I wanted to find out, Duncan, what got you interested in analgesia?
[00:01:19] Speaker C: It's a pleasure to be here, Nagi, and that's a great question. To start with, I'll try and make this short. Growing up as a kid, I was fascinated by two things wanted to be a veterinarian, but wanted to study memory. I was fascinated by memory and so I set off on this journey of becoming a veterinarian. Wasn't sure how the memory piece was going to fit in. And then during vet school I was taught by Alex Livingston and Avril Waterman Pearson and I'd learned that what drives pain, the mechanisms that drive pain are very similar to the mechanisms that drive memory. And so suddenly here it was.
I could study memory by working in the pain field and that was solidified as I was getting towards the end of vet school into the clinic and realized that we just weren't doing a good job of recognizing pain, certainly not a good job of treating it. Our whole approach to pain seemed to be very backward. And so for me, that brought everything together and I made the decision I'm going to study pain and hopefully make a difference. Make a difference to clinical practice.
[00:02:35] Speaker B: Yeah. Relief from pain. Yeah. In fact, and I first remember meeting you quite a few years back, well, not meeting you, but hearing you speak. The first time in I think it was Denver might have been no, San Antonio at An Mean, where you were talking about cancer pain. And this was something that really wasn't being addressed at all. And that's where I first heard about Amantidine. And so started using Amantidine, I don't remember at that time as an NMDA receptor antagonist, but certainly started using Amantadine there and then. I think it was the first time we actually met. And we were on a medicam roundtable or panel quite a few years back and I was obviously very interested in medicam. And then we both worked on the AFP ISFM and Safe Guidelines back in 20 that were published in 2010 and certainly need updating in a big way because at that point, we were still saying, got to be really careful with cats with chronic kidney disease, and we know different things about that now. But what drew you then to osteoarthritis in cats? In the superior species?
[00:03:54] Speaker C: In the superior species, that's right. Well, firstly, let me say those panels, and I remember being on that panel with you. And the other panels I have been lucky enough to be on.
I cherish those times, those moments, because it's an incredible opportunity to talk to colleagues in depth, in detail. And many of those panels have led to and initiated improvements and leaps forward in how we practice veterinary medicine. So, yeah, I remember that very much. Enjoyed it.
Why did I become interested in joint pain in cats? But it goes back a long way. And again, I've always been interested in movement out in nature. And I think as I would watch cheetahs and other big cats on the TV, watch the way they moved, and then watch domesticated cats, I just think it's such a beautiful thing, the fluidity of movement, the grace of movement.
It's amazing. So much has to come together to make that happen and in such a perfect way.
And so then as I become a veterinarian and I'm interested in pain, it was obvious to turn my attention to cats.
Why are the cats I'm seeing moving in a stilted way? Why do they appear to be have trouble moving? Why has the fluidity of motion gone?
Why do I hear owners caregivers talking about cats not being able to jump up and jump down? And as I thought about that, I then realized there was a dearth of information both about the disease, joint disease in cats, as well as a dearth of information about how we might approach treatment. And of course, then I started to get into it and realized it wasn't because no one had bothered to address those areas. It's because we couldn't because we didn't know how to measure pain. And so that's been a focus for, dare I said, a couple of decades, trying to figure out how to capture that information.
How do we measure because until you can measure something, then you can't move forward with treatment.
[00:06:17] Speaker B: Yeah, and I remember that first paper you did when you were looking at accelerometers in cats and using that sort of to go back to the conclusion that well, given that these cats and again, not this being an ad for an NSAID or anything like that, but because you'd put these cats on an NSAID and now they were moving more and therefore that was indicative of the fact that they had something that the NSAID corrected prior to or alleviated prior to this. Then you did that unbelievable paper with Wendy Simpson where you looked at cats of all ages, 100 cats, 25 in four different age groups, and found that looking at the different parameters, both radiographically from an orthopedic exam and these were presumably healthy cats or cats without OA, doing orthogonal radiographs of every body part short of the ears. I'm imagining. And you found that joint changes start I like the term joint changes better than OA because it has a particular definition in human medicine. But that joint changes and joint disease starts as young as one year of age and it gradually increases, which seems counterintuitive given the structure and the kinetics of this beautiful, graceful creature that is so incredibly ridiculously flexible.
That was a fabulous paper. Then you also did work on alternatives. When you looked at green muscle extract and glucosamine and chondrite sulfate. Yes, chondrite and sulfate, yeah. Looking at diets there.
[00:08:00] Speaker C: Yeah.
So you've mentioned papers and how do they get into the area? It just reminded me of the first paper in this area that I published in, I think, 2001. And it was just looking at the utility of ketoprofen and meloxicam in cats with joint disease, joint pain. And it was so difficult to get it published because it wasn't on anyone's radar. And there were questions around, well, were these cats actually painful? How do you know? And that was like a good red flag to a bull. Yeah, I'm the bull. Yeah, that was a red flag.
[00:08:38] Speaker B: That was the red flag. And you were charging.
[00:08:41] Speaker C: We're going to figure this out.
[00:08:43] Speaker B: You're on.
[00:08:43] Speaker C: Yeah, we're going to measure joint pain in cats.
[00:08:47] Speaker B: Yeah. That's fantastic, because when I did a paper in, I think it was 94 95. 95, it was published on transdermal fentanyl patch just to see whether we could measure transdermal fentanyl, whether transdermally delivered fentanyl could get into was measurable at serum levels.
I was asking a very simple question, and that was easy to publish because that was just a pharmacokinetics or pharmacodynamics, I never know. That stuff paper. It was just I slapped this on. Does it get into the bloodstream and how long does it but very much simpler, actually, with a colleague of yours, Mark Papich did the measurements. God bless.
You know, you mentioned this. You sort of alluded to the translational medicine aspects and the measurement of and what do you do in your institute, or what do you call it, the program?
[00:09:43] Speaker C: There are two umbrellas I like to position myself under. One is the Trip program, so it's a translational research in pain program. And that, if you like, is my lab, my group. I've been lucky enough to put together a wonderful group of people to work on these problems, come up with solutions, and then that fits into a slightly bigger umbrella. Comparative Pain Research and Education Center. Relatively new.
And that really speaks to the fact that it's all very well doing research and making discoveries, but those need to be communicated to all stakeholders, owners, veterinarians, the whole veterinary team, industry, industry. And so that center there is not only to facilitate, to help initiate research, research ideas, but as a platform for good education. So you'll see a lot more coming out about that in the near future.
[00:10:45] Speaker B: Yeah. And maybe including in that also breeders as a special group of.
[00:10:50] Speaker C: Absolutely.
[00:10:51] Speaker B: Special group of.
[00:10:53] Speaker C: And I think it's all too often, I think, in veterinary medicine we think of us and them. Yes, we are the authority and them, whoever them are, owners, breeders, industry, the other people, as information is going to flow from us to them. And that's so incorrect. Yeah.
We need to be communicating to all stakeholders and learning from each other.
[00:11:21] Speaker B: Absolutely.
[00:11:22] Speaker C: Got pieces of a puzzle and no one's got the whole puzzle.
[00:11:25] Speaker B: Well, and this is something the breeders have such a depth of knowledge, such deep, deep knowledge about particular things, some about husbandry, some certainly about certainly about genetics way more than like coat color genetics and form genetics than we as veterinarians have. We have a broader picture about more things. But this is incorporating or, including the people living with the cats, leads perfectly to the next thing I want to ask you about, namely diagnosis. What role does the orthopedic exam play and how best is joint disease diagnosed?
[00:12:07] Speaker C: Sure.
[00:12:08] Speaker B: Yeah.
[00:12:08] Speaker C: So maybe just to reflect on how things have changed over the last few decades. So when I graduated, the diagnosis of joint pain in cats was really focused on the orthopedic evaluation, which was the hands on manipulation of joints. And over the years, we've seen important and appropriate changes. I think the first change was a realization that owners are important in this, the caregivers that we don't see what we need to see when cats come into the clinic. We need to be capturing information from owners that led to the development of, evaluation of and validation of questionnaires to capture the appropriate information.
And then on top of that, the realization that the orthopedic examination, the hands on is nothing without observation, our observation, careful observation, but also observing cats in the home environment where they actually move.
[00:13:10] Speaker B: Rather than just crouch and hide, exactly.
[00:13:12] Speaker C: Where they're performing their activities of daily living. And nothing good has come out of COVID except the realization of the value of video from the home environment.
One day in March 2020, we were seeing clients in the clinic, the next day we were not. And we had to pivot. And I think what we learned from that was the value of looking into the home environment. And so now I think video from the home environment of cats moving around, performing the activities of daily living is so valuable. So those are the changes, the way the orthopedic examination has been enriched. But they wouldn't work unless there was an overlay across all of that of behavior, understanding normal cat behavior, understanding how it's perturbed by joint pain, understanding normal cat behavior and needs in relation to what happens when we bring them into the clinic, what happens in the clinic, and what happens when they return home. And that's the crucial overlay here because none of it works without that understanding. We can't interpret what owners are telling us, we can't interpret video and we're not going to do a good job with a hands on evaluation in the clinic.
[00:14:27] Speaker B: Yeah, what you're saying makes me think of the older middle aged to older cat who is a bit dehydrated, has lost a bit of muscle, has lost a bit of weight, and we're concerned about the dehydration and the weight loss. And so we're maybe putting them on an appetite stimulant and changing the diet and this sort of stuff, rather than realizing looking at the whole cat and realizing that, yeah, they're also having difficulties jumping onto the bed or they no longer can crouch over their bowl as readily or don't feel as comfortable because there's some other cat or dog or machine that makes funny noises at erratic times and therefore they don't quite have the because they're in pain that they don't have the confidence, and that's why they're dehydrated, and that's why they're losing weight and losing some muscle and the like. And so it all points together.
[00:15:23] Speaker C: And I think what is really important to cats is the 3D use of space. So dogs, us, we're all 2D, we go in essentially two directions.
Cats need that vertical movement and when that's taken away from them through joint pain, a lot of other things start to become problems. Fear, anxiety, other behavioral issues.
[00:15:48] Speaker B: Yeah, the 3D for vantage, for observation, looking for the threats should they come, being also curiosity.
And then their bodies are also designed for really this stretching and upward stretching and the whole scratching thing as well. So, yeah, it's very important, the behavior aspect too.
[00:16:11] Speaker C: I think earlier you mentioned you asked me about translational. Yeah, yes, let's just hit that up. So I'm a big proponent of this. There shouldn't be human medicine and then veterinary medicine and then environmental studies.
Every area has something to learn from the other. And I think, fundamentally, when I just look at the problems in human medicine and I know the same diseases exist in cats and dogs, there has got to be something we can learn from cats and dogs to help human medicine and to boot. We're going to learn more about cats and dogs and be able to treat them better. And we should be looking as I think we do a reasonably good job of at human medicine to improve management of our veterinary species. So something I'm really interested in, I spend a lot of time doing is looking at how we can position problems in pets, problems in cats and dogs as a model of the human condition. And that's the platform from which we can then start to really engage in truly translational and comparative research.
[00:17:25] Speaker B: But I think it also goes the other way too, in that given the fact that human medicine has benefited so much from the use of animal models, they need to give back to us too. And again, not having it be an us versus them thing, but rather that it really is a one health situation. Absolutely. And that I remember back in the late 80s when you were probably still in vet school, or maybe not even in vet school yet. I don't know.
[00:17:59] Speaker C: I was well through vet school in.
[00:18:02] Speaker B: The late eighty s. Okay, good. And I was taking cats down after hours to different hospitals for after hours, so I could get them in for cardiac ultrasounds by the human text and radio iodine and various other radioactive treatments and evaluations. Because I just sort of boldly thought, you guys have benefited from animal models, time to give back. And so I was just very cheeky about that. So we've talked about diagnostics, we've talked about also about using questionnaires as part of diagnostics, but then also we need to use our questionnaires and our reevaluations when we implement treatments. So the first thing I wanted to touch on with treatments was certainly NSAIDs have been for, I won't say a long time because nothing's been a long time in feline joint disease, but NSAIDs have been the cornerstone of treatment for us as they are in human joint pain. But one of the really interesting things that you with Margaret Gruen, or maybe Margaret Gruen with you discovered was that perhaps the way we've been doing therapeutic studies or therapeutic studies like drugs has perhaps been incorrect for cats. Who knows? Other species don't care right now about that. We're talking about the superior species.
Can you talk to.
[00:19:44] Speaker C: So I guess I'd kick off by saying we've got a lot to learn about study design.
And one of the reasons you're right, I've worked with Margaret Gruen a lot on this. One of the reasons we've taken a closer look at study design, particularly in cats, when we're trying to assess chronic pain, is the very high placebo effect.
Now, it's not a placebo effect as in the cat thinks it's getting better. This is maybe better called the caregiver placebo effect.
And for a variety of reasons this has been a real problem in chronic pain studies.
I think there are many potential reasons, but one is that everyone knows there's a dearth of treatments available. So when one is engaged in a clinical trial, one might be looking to see a positive benefit, cognitive bias. Right. Looking forward to having a treatment that is shown to be efficacious and gets approved and used.
And also I think another reason why the caregiver placebo effect is high is very often when you set up a clinical study, you take an owner from knowing their cat and watching it to now watching it a lot more closely. And so you've changed that dynamic, and maybe the interpretation changes with that. So there are all sorts of reasons why when you start a clinical study, the placebo effect is going to be very high. And we found in feline studies, it is high even when you set the threshold high, it's 55% to 75% as.
[00:21:29] Speaker B: Opposed to the usual 33 that you expect. Yeah. Yes.
[00:21:34] Speaker C: And so we've looked at study design. One of the things we worked on while Margaret was doing her PhD with me was to look at deterioration instead of improvement at the front end. So we were seeing this very high placebo effect at the front end when a study started comparing two groups, placebo and active. But when we blindly, that is, owners didn't know we were stopping the active treatment in that group. Owners saw a return of clinical signs.
And so there are other ways of setting up studies that I think might help us help us understand what truly is efficacious for joint pain in cats.
[00:22:16] Speaker B: Yeah. So it sounds as if what you're saying, or the way I have understood it, is that perhaps what we need to be doing is starting everybody on drug and then switching half of the individuals to placebo without them knowing it's still the blue pill. Or everybody started with one red pill and a blue pill. Or maybe in this country, it's better to say a green pill and a yellow pill.
And then everybody keeps on the green pill and the yellow pill, except at some point the green pill gets what's in the yellow pill, which is placebo.
And then to see look for that deterioration, to see if it really makes a difference, because you still have the eagerness and the observation. But was there not also a thought that the effect of more interaction, more loving interaction between the cat and between the person and the cat might also positively affect how the cat was feeling, that we couldn't parse that out from the drug effect either?
[00:23:17] Speaker C: No, that's right. In fact, we did have some data, we generated some data that confirmed that that as a result, in the placebo treated cats as a result of that interaction, a percentage medically small, but a percentage of the cats actually got better. They were moving around more playful, happier. And we actually had some objective, solid, objective data on that. And I think that speaks to the importance of that interaction.
And as a profession, we have ignored that. We've really focused on drugs, on therapeutics, on diets, on supplements. And I think we should be talking more about the biopsychosocial model of pain.
We should be thinking about how do we change, modify, leverage the interaction of owners with their pets as part of the approach of treating pain.
[00:24:23] Speaker B: Yeah, not just treating pain. Maybe we can do a podcast on that, too.
We now have, and it's been available in canada for some time, and I think maybe other parts of the world, too, but certainly in Canada, it's just been released in the States, is using frunovetmab or cilencia in cats. And it's just been remarkable, again, work that you and Margaret have done, and it's just been remarkable. Do you want to just briefly touch on that?
[00:24:57] Speaker C: Sure.
[00:24:57] Speaker B: Yes.
[00:24:57] Speaker C: So we were the first to look at Franivetmab in client owned cats, as we call them, own cats. This was part of Margaret's PhD, a relatively small but highly controlled proof of concept study. And that was the first time in my clinical research career that we had ever seen dramatic changes in the treated animals. Now, we didn't know which ones were being treated, but we were getting feedback from owners that was very, very positive. We were seeing the cats when they came back in the clinic as much improved. You don't ordinarily see that in chronic pain studies of therapeutics. So the dramatic changes we saw there have actually panned out in the subsequent clinical studies, the field studies, the pivotal studies.
The efficacy is solid. It really is. And I think the other thing which is very exciting about this is that now we have a solution that doesn't rely on oral medication.
However good you or I or our clients are at giving oral medication, it's a burden. And I think having an injection to bypass that, to alleviate that reliance on.
[00:26:17] Speaker B: The oral routine once every 28 days, or maybe in reality it's going to be once a month, isn't it?
Which sort of comes cycles right back to your interest in memory. Because when we're talking about joint pain and anything that's chronic pain, we're talking chronic neuropathic pain, where in essence, I guess, and maybe I'm just romanticizing this, but I'm envisioning it as the way the nerve fibers are firing has actually developed a new memory, a new way.
[00:26:49] Speaker C: Of correct, of doing things.
[00:26:51] Speaker B: And so we have this chronic neuropathic wind up overstimulation, alodynia, hyperalgesia, et cetera, just in the few minutes we don't have because we're already over massively in time. But it's so fascinating, it's so great to talk with you. Any last tips? If there were three things, let's say I won't make you look for ten, just three things that you might think of that you really want people to take away from looking at cats and joint pain.
[00:27:25] Speaker C: And can I answer this from the veterinarian centric perspective? Okay. All right. So the three things are embrace the owner as a team member. Listen to what they say, but also talk to them and provide them with the educational materials that we have, but also listen to them and be willing to be educated by owners. They know what's going on. The second thing would be to capture video from the home environment.
You have to give clear instructions, and you've got to figure out how to receive the video and store it how to assess it, how long it should be, how long it should be.
[00:28:07] Speaker B: Yes.
[00:28:07] Speaker C: So there are a few things to sort out there, but it is an incredibly important, incredibly valuable part of the assessment. And then the third thing I would say, because you're limiting me to three, is seek out an understanding of cat behavior, because the experience of a cat visiting your clinic and then returning home is not going to be a good one. Unless you understand cat behavior, unless you understand cat needs and you understand how to make that experience pleasant for the cat and the owner.
[00:28:46] Speaker B: Yeah. And they go on that for eons. Thank you very much. This has been really fun.
[00:28:52] Speaker C: You're very welcome and enjoyed it.
[00:28:53] Speaker B: So yeah. Margie Shirk interviewing Dr. Duncan LaSalles. And thanks all for listening.
[00:29:02] Speaker A: Thank you for listening to this episode of All Cats Considered. We hope you enjoyed this interview. For more information on the topics discussed during the episode, please be sure to head over to Catvets.com and explore the links in the podcast description. And please be sure to subscribe to this podcast and your platform of choice so that you don't miss any episodes as we release them. Have thoughts or ideas about the interview you heard today? Share them with us. Leave us a comment on our Facebook page, or shoot us an email at
[email protected]. Thank you for joining us today.
Sam.
