Pain management in cattle | Veterinary Videos & Podcasts

OK, so good, good evening, everybody. I think we can start because we are already quite a lot of participants. So happy to be here with you today.

We should welcome people from more than 15 different countries tonight. So my name is Audrey Brunet. I am the marketing and technical manager for Rein for Central Eastern Europe and the Middle East and Africa.

Welcome to this, webinar focusing on cattle pain management. We are two experts, Professor Rafael Goto and Doctor Luke Duel. So before we start, just some technical information.

I would like you to have a look at the chat room at the right side. Some of them already have find it because they have they wrote some comments. This chat room is only for comments or technical issue, but please, if you have any questions, can you use the Q&A boxes?

It's better than the than the comment in the question in the chatt, and we will answer your question during the session or later by email if you don't have time to answer all your questions. And yes, and in addition to that, we will also organise during the presentation some pool, different pools, so we will ask you to, to participate and give your input by answering this pools. So that's it for the technical part.

So you may wonder why we decided to develop this webinar. So as everybody knows in one of the most misunderstood aspects of animal welfare and especially many people believe that cattle are considered as very resistant animals and they do not express or feel pain. And we believe that pain management should be a focus area for both producers and veterinarians.

And while a certain amount of pain of work can be healthy or even beneficial, pain can often lead to negative long term consequences on the, on cattle and impact, of course, the return on investment of the farm. And we all know that indeed Apia will make better milk, and learning how to recognise, diagnose, we, and treat pain is crucial for both vets and producer. So today we want to go deeper into the pain management topic.

We have our first speaker, Professor Rafael, who will cover widely the topic of pain management from detection and grading to treating different painful conditions with the help of a non-steroidal anti-inflammatory drug. And with our second speaker, Dr. Luke Durrell, we will focus on the close relationship between infection and pain and how curacer duo, our combination of c and ketorofen can help you to manage two problems at the same time while maintaining your milk production.

So now I'm very happy to introduce our speaker. So the first one will be, like I said, Professor Rafael Guo, who is working at the vet school in Nantes in France. And he also graduated from this school in 20 in 2001, sorry.

And he's working for the Department of Farm Animals and the farm animal health and public health. He's teaching activity deal with individual and population medicine in cattle, both in clinic and in farm. Professor Rafael Grotto is also a diplomat and a past president of the European College of Bovine Health Management and as well a diplomat of the European College of Animal Welfare and behavioural Medicine.

The second speaker is Dr. Burrell, like I say, he's currently working at Verbach as a global technical and medical information manager for the ruminant segment. He also graduated from the same vet school in Nantes, but a few years earlier than Rafael.

Dr. Dre previously worked on the film during 18 years and he's particularly interested in the herd health management as well as diagnosis of cattle disease, mineral nutrition inominant, karmatitis, and the quality of milk. And he is a member or a former member of different societies in both friends in the US like the National Mathetics.

So now let's move to the first presentation with Rafael. So Rafael, the screen is yours, and yes, please do not forget, if you have questions, use the Q&A. OK, thank you very much Sorei, for your kind introduction.

And if you are not familiar with friends, just to know where or not it is located, so where with Luke, we did our study. If you are familiar with the cartoon Asterix, it's not so far from the from the village and in the film portion. So, first of all, I would like to warmly thank Via Bach for the kind invitation to give me the opportunity to share with you some insight into pain management in Qatar and as I mentioned, the idea of the presentation need to be as interactive as we can.

So we prepared some poll, but, I, I, I, I proposed maybe to make some different stuff along the presentation to be sure that you have time and opportunities to, to ask questions. And so one of the goals of the presentation in addition is to Investigate the, the putative interest of non-steroidal anti-inflammatory drugs or NSAIDs, especially for pain management in cattle. So the outline of the presentation will be the following one.

So in the first part, we will deal with pain, just to be sure that we talk about the same thing, so we will deal with the definition of pain and we will see that there is probably not one pain, but different ones and also the link with inflammation. In the second part of the presentation, we will deal with how to detect pain in cattle on, on daily practise. In the third part, we will try to, to have, I would say a global approach, which is named the 3S for suppressed substitute and through pain.

It is a framework to approach pain management in Qal, so I will share that with you. And in the last part, we will deal with the interest of NSAIDs as painkillers, and I will try to have an evidence-based medicine approach. To show you what are the interests that you can expect from treating cattle, especially those suffering from pain with NSAIDs.

So if we move to, to the first one, pains, inflammation, as I mentioned, I would like to, to open the presentation by the first question, by the first poll. I would like to know what would you say? Cattle are a species.

that doesn't feel pain. Cattle are a species, for that does not express a lot of pain, or cattle are a species that expresses pain in its own way. So, I think it's not the right poll.

I think it's another question, probably. Yeah, please. So I would like to have your opinion on that.

Thank you very much. So So don't hesitate to vote if you consider that cattle doesn't feel pain at all or they do not express pain or they express pain but in their own way. OK, let's see the results.

So, you're right, guys, effectively, indeed, as it was mentioned by other as an introduction, a lot of persons consider that cows do, do not feel pain. Some others consider that they do not express a lot of pain, but as I, I will show you afterwards, and I hope that I will convince the 26% that the answer to, to the second option, that cattle do express pain, it's frequently a problem of condition of observation. So if we try to, to move on on the presentation and to know exactly what is pain or, or what are pains in, in, and it's not a singular condition.

The, the only solution for us is to have an extrapolation from the definition from humans. And so I copy paste here the definition of the EASP, so the International Association for Study of Spain. They have a new definition in July 2020.

And so pain is defined as an unpleasant sensory and emotional experience. So sensory and emotional are towards very important in the definition associated with or resembling that associated with actual or potential tissue damage, OK. So I think that if we try to, to put into practise, I would say this definition, what are the most important consequences of such a definition?

I think first of all, We think to consider that pain is always a personal experience that can be influenced by varying degrees of biological, psychological, social factors. For instance, we know very well that in humans, for instance, pain sensitivity, is different, for instance, between, between male and. Man, for instance, it's also depending on the age, sometimes also from a religious consideration.

We know also, and, and then if we introduce that into cows or into cattle into practise, it means that two cows suffering from the same condition will not express or will not suffer of the same degree or intensity of pain. That pain and no C-section are really different phenomena, OK? And so it means that pain cannot be inferred solely from activity in sensory neurons, OK?

You are really emotional also, it's not just about you know C-ception. It means also that through the life experiences, individuals can learn the concept of pain, so you have a sort of learning approach and sometimes also we see that afterwards, especially during chronic pain, the, the, the nerve, the central nervous system can be a bit troubled, I would say, and, and then you have a decrease of the threshold for pain sensitivity. It may have adverse effects, even if normally it serves as an adaptive role, it may have adverse effects, OK, and verbal description is only one of the several behaviours to express pain, and I think it's probably one of the most important extrapolation from what we can do from the human definition.

Usually, we say that for human doctors, it's easy to know what the, the patient is suffering from because he can, he can give a sentence, OK? He can talk to you, he can say, OK, I have an injury to the arm, to the leg, etc. And I'm suffering from the shoulder, for instance.

But sometimes they have to take care about young babies that are not. Able to, to, to speak, or they have to treat some person with mental deficit, for instance, which are not able to, to explicit clearly the things. And so it means that you need to move from what we call a self-assessment to a assessment.

So it means that the assessment of pain, especially in cattle, but it is the case for all the animals. It's not done by the, the animal itself, but it's done by the humans. So either by the farmer or by the vets.

Or by any other person, but at least not by the, by the animal itself. And so I think that it's really one of the main important things and we will see afterwards that all the works which were done to detect pain in humans and especially in those who were not able to express their pain, such as young babies have served as a basis for some work on, on pain detection in animals and especially in cattle. Then, to move to the link between pain and inflammation, another question for you, guys, I would like to know what would you say?

Inflammation is necessary for the healing process of the animal and should not be fought. Inflammation is harmful, OK, for the animal, and, and, and, and you need to, to, to ban it. Or last but not leastO are very frequently concerned by inflammation.

So you have the possibility normally to, to vote for more than one, I guess. OK, so what are the results? OK, so, well, it's pretty divided, so you are 16% considering that You, you, you need to let inflammation going on because it's, it's necessary in the healing process.

We will see afterwards that in a certain part, you're right, the majority, or almost 47%, 1 out of two think that it's harmful and that you need to treat that. We will see that you're right now, so everybody is right today, it's fine, and that cows are very frequently concerned by inflammation, 38% to to think that, and we will see afterwards that yes, cows are really susceptible to inflammation. So, Why I told just before that both were right, that those considering that inflammation should be treated or should not be treated.

It's depending on how you are in the healing process, I would say. So following an infection, and I think Luke will address this issue, but also following some physical or chemical stimulus or tissue stress such as surgery, for instance, you have inflammation. All these conditions, all Stimuli to inflammation and inflammation, as you mentioned, and this is why you are right to consider that it is a natural phenomenon.

OK. The, the goal of inflammation normally is to fight against infection, especially helping the recruitment of, of neutrophils, for instance, also help in tissue healing and recovering. And it also helped to adapt the stress response and especially to adapt homeostasis.

So normally, if inflammation stays under control, it's beneficial for the cattle, for the cattle, for the humans, for everyone, OK. The problem is once inflammation is too strong and that the animal cannot cope with that, it will lead to the bad adverse, I would say the bad side of inflammation, and then it will lead to an increased risk of inflammation and sepsis. OK.

It will lead not to help tissues healing, but contrary to that, it will increase the likelihood of fibrosis or tumorization and instead of helping the, the, the, the cattle or the animal to cope with homeostasis, it will lead to an increased risk of Metabolic and autoimmune disorders. So the only question is how to know where is the limit between what we can call natural inflammation and the natural course of infection, for instance, or healing or recovery and the bad side of inflammation. I would say that.

Really, the observation of the cow is really the key. You need really to see the cattle, do the clinical signs persist for a long time. If the cattle looking as not comfortable enough, OK, to, to live in this environment, so it's really observation of the animal because at the moment, to the best of my knowledge, we do not really have some blood test or, or some cosine test to, to, to do to be sure that inflammation is really on the bad side.

But really, it's following and monitoring of the animal, which is really the most important. OK, so the goal is really to avoid excessive and uncontrolled inflammation. And so to do that, really, the, the, the, I would say the pivotal or the main medicine that you have all enhanced is non-steroidal anti-inflammatory drugs for sure.

NAIDs. They are, they have an anti-inflammatory action through the inhibition of prostaglandin synthesis. For sure, they have also an analgesic effect.

By two ways, they decrease both central and peripheral sensitization. I think it's very important to keep in mind that all the more recent, all the, the modern and recent NSAIDs have both central and peripheral action to decrease the pain and sensitization. They have also, as you know, anticyrexia.

Direct by action on hypothalamus and last but not least, especially interesting in metritis or chole mastitis or or toxinic mastitis. They have also an anti-onitoxinic effect via the inhibition of inflammatory mediators. So a lot of positive effects that could lead to promote the use of NSAIDs.

So, as I told, many indication, hyperthermia for sure in the case of BRD also calvia, toxicic disorders, mastitis, nephritis, but also pain, I would say provoke pain such as surgery or different disease. In terms of side effects. It's, it's frequently mentioned that NSAIDs can live in, in humans, in animals in general, to acute renal failure and also gastric ulcer.

So, I, I just have a look at the pharmacovis data in France. I don't know if it's mandatory for you in in a lot of countries, but I guess it is. When we look at the, at the reporting of vets.

Regarding the side effect of NSAIDs, it's almost none. So maybe they are underreporting, and it's always possible because it's not always very easy or comfortable to do such a, such a reporting. But to the best of my knowledge, and we treat the faculty, a lot of cattle with NSAIDs and especially repeated injection, as long as you do not do really, chronic treatment, I would say there are no risks and most of the time, we will make a one-shot injection or maybe 2 or 3 injections.

And I think with such a reduced duration of treatment, the risk, especially of gastric ulcer, is really very low in cancer. And I don't know if you, I don't know if you remember, but the 3, the third option, of the question was, do you consider that cows are frequently concerned by inflammation and 38% of you consider that yes, cows are frequently the site. Of inflammation and it's clearly true.

And one of the key moments for, for an adult cow is really around Calvi. So on this picture, I take this picture from a very brilliant publication from Bradford on the Journal of Dairy Science in 2015, talking about the diversity and sources or causes. Of inflammation in cattle.

And here, if you consider this figure with here the time from parttuition to the peak of affectation and here in the y axis, the systemic inflammation, you can see that you have two patterns of cows. I would say the blue one and the red one to facilitate the interpretation of the figure. The blue one are the cows suffering from inflammation, inflammation due to the cytokine released after calving, OK, especially through the uterine evolution and the metritis sometimes around parturition you have also a gut which is more leaky than usual.

Increasing the likelihood of LPS circulation in the blood, so increasing the inflammation status of the cows, OK. You are for sure social stress and also oxidative stress around dry period but also around calvin. All these together lead to what we call inflammation bursts.

So a cow around calving is really the site of a burst and and a lot of inflammation, but you have two kinds of cows, those which will cope with this inflammation with a very fast and rapid resolution. And usually this animal will have a very fast and strong metabolic adaptation, very good fertility, normal cycle, etc. OK, and not, not so much disease afterwards.

But the problem are the red ones. These cows suffering from slow resolution. Usually these cows are also those suffering from, I would say persistent hypocalcemia after calvin.

And usually this cow will add all the problems that the cow can suffer from during the lactation. And so they will have an increased risk of negative energy balance, an increased risk of metabolic disease, and an increased risk of fertility. OK.

So really the goal for you and I think it's especially interesting to follow, especially the cows with chronic endometritis after calving. You can be sure that the cows suffering from chronic metritis with failure. Treatment, etc.

Are probably the red one, the red pattern, and this one, the red, will probably will benefit from NSAIDs while the blue one normally cope with the, with the inflammation. OK. So I would say that the blue one corresponds to the normal healing process or recovery process or cope with inflammation while the red ones need, need to be treated, especially with NSAID.

So the prevention and the control of inflammation is really crucial. So if we move now to the second part of the presentation about pain detection in cattle, OK, what are the criteria, what are the farmer perspective, the vet perspective, do scoring grid exist and can be used on daily practise? I would like to know, and that's the third question for you, the audience, I would like to know for you among the following criteria, which ones do you think are the best to consider to detect pain, OK, among cattle?

Are the physiological criteria, behavioural criteria, and those criteria. OK. Which one would you use?

Do you consider at the most relevant to detect pain? OK, let's see the results now. So behaviour at 70% good, very good, really good audience, and really, really clever tonight, so.

You're right. The behavioural ones are probably the most adaptive because physiological for sure when you have pain, you have an increase of the heart rate, you have an increase in the cortisol secretion, you have a lot of modification. But from a practical point of view, you, we don't have cosy tests to measure that.

I will treat that afterwards. Maybe the new IoT or the monitoring device will help maybe to detect some physiological criteria, but on a daily basis, on a routine practise, there we don't have such cosite test to do that. And so technical criteria for sure, when a call is painful, probably.

This will lead to a decrease of milk yield, decrease of fertility, but these are too late. And when we asked to the farmer, we did a study several years ago and we asked to the farmer from their perspective, what are the the the the the most relevant criteria to detain. With no ambiguity, the report only, and I would say mainly behavioural modifications such as general behaviour modification, but also in it's very important facial expression as you can see here on the picture on the right of the slide, OK, with an extended face, tension of the muscle, OK, exothalmia.

The here really behind the, the head of the cattle. So facial expression, the gait and the posture for sure, especially when the cows suffering from colic or lameness, but also vocalisation and the whole, the whole consider that decrease performance are, I will say specific signs but not sensitive enough because too late the, the, the. They occur too late in the painful procedure or in the painful process.

So from a farmer perspective, there can really be considered as a really early and reliable signs for detecting early, earlier as possible pain, OK. But interestingly, they also reported fever as, as a sign of pain. So I will say that on a certain point of view, it's not, it's not false because when you have infection, you have hyperthermia and, and lots of infection and I think we, we address that you have pain for sure, but you have also a lot of other conditions that are very painful for the cow and that do not.

Necessa to fever. I think, for instance, on digital dermatitis, mortelar disease, it's really painful for the cattle for sure, but you don't have fever for that. So sometimes there can be a confusion in the head of the farmer, leading maybe to treat pain using antibiotics rather than NSAIDs, OK?

So detection through the visual appraisal, either by the farmer or the staff is really important. And I think it's even more important because when the farmer called the vet, I don't know the situation in a different country, but at least in France, when, when, when a vet called the farmer. or, or more when the farmer called the vet, sorry, most frequently the cow is really restrained in a shoot or in a swimming chute, etc.

And so the possibility for you to look at the behaviour of the cow is really limited. It's really by questioning the farmer that you can have access to all the information such as modification of the behaviour, feeding behaviour, drinking behaviour, lying behaviour, etc. OK.

So, another question that we asked through that survey to, to, to the To the farmer were to consider if whether or not it was able to know what are the most painful conditions. So when we ask the farmer to make a sort of ranking, what are the most painful procedures that you, you, facing in your daily practise? Number one, lameness.

When you, when you had the leg disorders, fractures, and, and food disorders, OK. The second one was digestive disorders, and the third one was mastitis. OK.

Here, we don't talk about surgery, but just about disease. And once again, I don't know the situation in your country, but at the moment when we did that study in France, it was 10 years ago, I think probably now the situation has changed. But 10 years ago, When a cow was lame, the treatment was sex to fear.

When you have digestive trouble, the treatment was antibiotics, and when it was mastitis, it was a combination of steroidal and antibiotics through the intramammary gland, OK? But the reflex of the farmer, the first intention treatment never contained NSAIDs. And interestingly, the, the farmer consider that these are the most painful procedure, but on the daily basis, they do not treat pain.

So they can be a sort of paradox, OK. And in the same, in, in, in the same approach, we ask the person to rank some different surgery but also disease. So as you can see here, OK, we ask the farmer to rank from 1, no pain to 10, the, the worst pain existing, OK, some different disease.

And as you can see here, for instance, mastitis 4.3, choleom mastitis 7.3.

So it's pretty interesting because from my point of view, cholemastitis or toxinic mastitis can really be associated with an impaired welfare. Sure, but I'm not sure that it's so painful from or it's more painful than a classical mastitis when you have a big inflammation in the other. Probably that the farmer score of the higher cholemastitis rather than a classical clinical mastitis because you have a huge impact on on the general state.

So once again, there can be an amalgam between the intensity of the disease and the intensity of pain. I would say no surprise low amputation, fracture scored very high, but C-section in the middle. So I don't know your perception of that when, when you open the, the, the wall, the, the abdomen of a cow, OK, looking into the abdomen, opening the uterus, etc.

For sure, it's painful. So it, it, it's, there is still a paradox, OK? And even when you talk with the, with the, with the farmer, but it's the same with the vet and because we ask exactly the same question to the vets within the same study, we clearly find two variation factors when considering.

The ranking of the disease in terms of pain was exactly the same depending on the age, the the the fact if you are a farmer or a vet or male or female. But when you look at the grade and intensity, it was systematic 1 point above for female compared to male. And when we asked the question to you.

Farmer or young vet, the, the ranking once again was the same, but the grade, the mark, the intensity of pain was 1.5 points above the old ones. So as I mentioned, as an introduction, you have a perception of pain.

It's not only about science, it's also about experience, but also consideration of the society per se. And so it's not always easy to just to, to look at pain really only on scientific evidence and scientific aspects. OK.

And so once again, when we compared the ranking either for adult or calf, for different disease, when you look at the, at the ranking in terms of marks given by the farmer or the vets, you can see that for sure the mark can be a bit different, OK. Sometimes for C-section, depending on who is doing the procedure and taking the, the kick of the cow because it's Painful, probably the vets scored a bit higher here. But when you compare both, probably the perception of the two persons are not completely different, but my experience, at least in France, is that the vets are convinced that the farmer is not ready to pay for treating pain.

And on the other side, the farmers sometimes would like to discuss about pain management with the vets. But it doesn't really know how to, to, to, to discuss about that with the, with the vets. And I think that one of the problem is to make connection between both because when you look at this, and we, when you look at the, at the frequency of use of NSAIDs, there is probably a problem somewhere because there is really room for improvement.

OK. So pain do exist, but on a daily practise, sometimes pain is not treating as much as we can. OK.

So we need for sure to sensitise. The, the, the farmer and, and also to increase the knowledge. And last but not least, I would like to share with you the results of that survey, considering the type of products that the farmer reported to use to treat pain.

So in, in, in the vast majority of cases, they reported to treat pain using anti-inflammatory drugs. But as you can see here, very frequently they reported steroids or cortisone or dexamethasone. And even if the steroids are really useful and very effective to decrease inflammation, they are not effective to treat pain, OK?

They are not analgesic, they're just anti-inflammatory. So it means that from this perspective, we really need to, to, to teach to the farmer what are the best products. And interestingly, almost 30% of them answered that they use antibiotics to treat pain.

So on one side, they are not really incorrect because if the pain is caused by an infection, by treating the infection, you can expect to, to, to decrease pain for sure on the longer term. But on a very short term for the comfort of the cow, for the welfare of the cow, NSAIDs should be really the key. So once again, we need to sanitise the farmer to what are the good products to treat pain.

And when we ask to the vets how they proceed, so here you can see two columns. Here is for Europe in red and here in peak is F is for France. OK, so it allows you to compare the, the French habits of, of vets, I would say in comparison to the rest of Europe.

It was a survey, conducted in 2006 under the, the supervision of John Oxley from Nottingham University at this, at this time was in Massey University in New Zealand. And so we, we ask to the farmer when facing a castration, a C-section, aro amputation or dehorning, dehorning in calf, do you use systematically NSAIDs, general anaesthetics, so mainly gazine, local anaesthetic, OK, or none? So as you can see when you look at the different results, you have some differences, clear differences.

For instance, in terms of use of NSAs, so I don't know the situation in a different country, but at at least at the time of, of the, of the, of the study, you can see a really big difference between the systematic use of NSAIDs for C-section, depending if you are in, in the rest of Europe or in France. And it's not a question of regulation. It's clearly a question of use, OK, because they are not used to, to, to do that.

Regarding the use of general and local anaesthetic, it can be explained, at least at the, at the, at this time of the study of regulation, because in some countries, you can, for instance, deliver some anaesthetic, even local anaesthetic or general anaesthetic to the farmer in order to do castration and dehorning. In other countries you can't, so we can explain the difference in terms of use. But interestingly, in, in, in, in some other cases such as castration and dehorning, you can see that.

In a lot of situations, sometimes you have no analgesia at all, no anaesthesia, no NSAIDs, etc. And clearly here there is room for improvement. I think it's not acceptable now from a vet perspective to not give advice to treat pain in such conditions, but, and that's a very positive thing in a lot of situations such as here amputation, you have already what we call multimodal analgesia, so it means the combination of NSAIDs.

Of general anaesthesia and, and local anaesthesia, all together to, to treat and to, to fight against pain. OK? So from a practical point of view, how to recognise pain in practise and at the end of the presentation, I, I would propose to you maybe stop to make a the first answer to the first question.

I think the most interesting thing is to look at the interaction of the animal together and the individual behaviour. And to do that, the farmer is really the best person. It's not when you arrive, the cow once again is in the chute, in the trimming chute, is restrained with a rope, etc.

So it's not very easy to know if the animal has an abnormal behaviour because she's already in a, in a particular position, OK? So the farmer is ready, the, the, the best person to tell you if whether or not The cows suffered from abnormal activity, abnormal posture, OK, from the line, but also from the tail, from the head, from the neck. And if there is any change in the gait or lameness, as you can see here on this picture, OK.

Here, look at the face of the animal with the position of the ear and also the nursery. OK. Another very practical assessment is to disturbance, what we call evoked behaviour.

OK. So you try to stimulate the animal, OK, by, for instance, squeezing it or just making some noise like this, OK, and just to see how the animal. Or not improved or reduced response and very frequently when you have pain, OK, you have reduced response to evoke behaviour.

So this is something which is really in favour of suspicion for pain. And you have also plenty of things and I'm sure that you look at it on the daily practise of poor body condition, skin coat condition, wounds for sure, or other signs of disease. And clinical signs such as increased respiratory rates, death, gasping, panting, sweating, trembling, increased muscle tone.

OK, if you have dilated pupils, the wide open eyes, exophthalmia, OK, depression, aggression, oracle or, or even a complete apacia of the animal, OK, and particularly in, in response to the show. All these, all these things can really give you the suspicion that the cow is suffering from pain. OK.

As I told you before, already the owner farmer assessment of the coca is really the best sentinel for early detection of pain, OK, and ongoing clinical condition for sure, including any treatment in progress should be part of the, especially the analysis to, to whether or not the animal is suffering from pain. And then moving to the grid, I see that in the Q and er session that there was a question, do we have some grids as they do exist in pets? The answer is yes.

You have some of them which are, I would say at the moment, pretty confidential because it's not published yet. So here I share with you the results of a survey that we completed 2 years ago with a veterinary students here, in the frame of his veterinary thesis. And we looked at the difference between cow, going onto a C-section and, and, and concomitant LC cow in the same herd to know if whether or not we will be able to find some clinical sign, very easy to build the grid to make a distinction between cows suffering from pain because for sure after the C-section you have pain in comparison to LC1.

And at the end of the study, we found that the combination of 5 parameters. Could help to have a very good specificity for a score of 2 or more. OK.

It was to look at the gate, OK, on the 5 scale gate, the locomotion locomotion scoring system, so the special one, the most widely used, the cardiac frequency, the position of the head, the hind lamp position, as you can see here, OK, really on the back of the animal, and the, and the harsh line, so the, the, the, the back line, OK. And then you had, depending until you had the score, depending if it's normal or not. And when we had a score above or equal to 2, then we had a very good specificity.

And tomorrow something which could be very helpful, OK, will be all the IoT, OK. So you have some, things which are still not yet on the farms, but probably in the coming years here, you have some robot delivering the feed with a camera looking at the face of the cow to know if whether or not the behaviour and especially the green mass. Can be detected on the face suggesting that you have pain.

But you have also here, these are the, the, the output that you can expect here on the graphic, the duration of rumination and the intensity of activity, you can measuring by a collar, so registering continuously rumination and activity and so forth. Where you have a very strong decrease of rumination or activity. Maybe it's not pain, maybe it's just a disease or maybe it's not a disease, it's just pain, but at least in both cases, this means that this cow deserves to pay attention from you.

OK, so I think that all these new IUT, what we call Internet of Things, monitoring device, can be very helpful in the future. OK. And the grid and it will be my, my last slide on this part of, of pain detection and then I will take some questions.

I think the, the, the, the, the, before using this new device, I think back to basics and visual appraisal of this animal. OK. So here I just give you the figure of what they call the pain phase, as I've mentioned as an introduction.

The some researcher took the what they call the grimace, scale pain assessment that is used in, in the, in the babies, in the puppy, OK, when they are not able to, to, to, to tell where they are suffering from. And so they, they make a translation, the sort of extrapolation of this grid for animals. And so you have, for instance, this, this grid which do exist for horses, OK?

And then you, you need to look at the ears if whether or not they are lower, OK. The contraction of the muscle above the eye, OK, the tense stair also is really important to look at the tension of the facial muscle, also the edge shape of the muscle, OK, and also the nostril if they are deleted or not, OK. And then they translated this breed from horses to to cattle.

So this is a work done by Clara and collaborators in Denmark and also as you can see here on the left side of the, of the, of the slide, it is normal cow, OK. And here on the right side of the Of the slide, you have a cow suffering from pain. You can see here the tension of the muscle, the tensions there here, the here which are lowered, OK, and on the back, and here the nostril also which are very deleted.

So once again, not too complicated to detect pain, just look at the, at the cows and especially the face, OK? And so ali in his collaborator proposed this grid, so they asked to look at 7 parameters. So the indicator or attention to stimulus, so as I told you before, evoke behaviour, but also how do the animal bear their head, OK, above withers, at withers level or below withers, OK.

The position of the ear, OK. Do the ears are forward and very active or are they backwards or even low? OK, the facial expression, is it attentive or neutral, or do you have a tense expression?

OK, so the response to approach, once again, the back position, is it straight or arch back for sure. And last but not least, also the lameness, OK. And then the sensitivity and the specificity of this grid was considered as pretty excellent by the, the researcher when the score was above or equal to 3.

OK. So yes, grid do exist in the literature and, and pretty practical and, and, and you can use. So yes, I, I can, I, I see a message on the, on the Q and A and yes, I can share a link.

I will, I can give you to and maybe they would send it back to you, the link for the cattle getscoring system, no problem. OK, perfect. Yeah, there was a question I would say because you, you show this graph, but are there any study for really showing the impact of pain on short and long term like some economical studies that have been done.

You mean the, the economic impact of pain, pain, yes, and long term on cattle. Yeah, so this is something that we will address at the end of the presentation with NSAIDs, but we can already say that from a scientific point of view, it's not very easy always to know exactly what is the economic impact of pain. Because as pain is not frequently very well detected.

Sometimes we arrive too early, too, too late to know exactly when the painful process was beginning and then to know exactly the, the duration of the period that we need to look at, and that's the first problem. But it's very clear that when you look at all the very painful conditions, for instance, lameness, you have an increased risk of cutting. When a cow is severely named, the risk of cutting is 5 times bigger.

OK, so for sure, it's, it's very detrimental on a clinical point of view. When you have mastitis, for sure, it's painful. You have infection, you have also the withdrawal time, but you have also due to the inflammation of the other, a reduction of the production potential of the, of the, of the other.

So also really detrimental. And for sure, when you have inflammation, chronic inflammation, such as after patuation and you have displaced abo, endometritis, increased risk of mastitis, etc. For sure.

Altogether, these conditions are, are, are, are really, I would say detrimental for the economic, impact of the things for sure. OK. So at the moment, no other question.

OK. You you couldn't can go on. OK, thank you.

OK. So now, let's move to the, to the third part of the presentation so how to approach pain on, on, on, on, on, on a daily practise, OK. And so I would like to share with you something that we try to promote in France for the last decade now, which is the 3S approach.

So I don't know if you are familiar with, but 25 to 30. Years ago to reduce the use of, especially rats, mices for experimental, things, experimental setting, experimental design, experience they developed what they call the 3 air approach, therefore reduce, reduce the use of animals for labs, things, replace, try to replace the animal by something else and refine. So try to find some, I would say most clever or more relevant and then refine methods.

And so we take a similar approach considering that we don't want to reduce or replace livestock, but ready to reduce pain. So we decide to promote this 3S approach. The first one is suppress, OK.

The first thing that you need to, to, to keep in mind is that very frequently you may make some intervention of the cow, you are the farmer, and sometimes it will lead to pain and sometimes it's useless. A very good example of that is tail docking. I know that for a couple of times.

A tail docking was written in the, in the book, in the husbandry book because it was supposed to reduce the risk of mastitis, reduce the risk of transmission of lesbospirosis to the milking, to the milkers, etc. And when you look at the data, there are no relationship between being tail do or not on, on the occurrence of mastitis. Excuse me, but it's bullshit, OK?

And so due to that, Tell docking in a lot of country was forbidden, OK. So that's a good example of how sometimes you can suppress pain. Another example for, for instance, that I give very frequently to my students, when you come in, in a farm to look at the, at the cows suffering from lameness and Clearly, the problem came from the feet.

You don't need to make a rectal palpation, OK? It's, it's probably not the most painful procedure for the cows, but it's painful anywhere. And if it's not, if it's useless in the clinical examination, just forget it, OK?

So first, try to answer the question of whether or not the, the pain source can be suppressed or not. If not, then try to consider that you can substitute. The, the, maybe the most painful method by a less painful method.

So I will give you an example just afterwards with the horning, with the horning, for instance, or even with castration, we know that all the techniques are not similar in terms of pain. And if you, you cannot suppress the, the, the, the source of pain and even when using the less painful procedure, you have still pain, then the idea is to cause pain by using early analgesia, so as early as possible. So for instance, when you do a surgery to use NSAIDs before the surgery rather than after.

Multimodal, so combining, for instance, NSAIDs to local anaesthetic, if we talk about surgery and adapt it, adapted to the intensity of of of pain, OK? So just to give you an example of this 3 years approach, if we take the example of the horning or this vitamin calf, we have solutions to suppress. The first one is to breed cows with the horn.

It can lead to problems, but it's possible in certain circumstances. Another possibility is to use genetic selection and to use bulls. We have the gene for absence of horn, OK, what we call the poll one, OK, and that's a possibility.

OK, but for sure we have some limit because the farmer need to accept, OK, to breed cows without horns, for instance, in France, in the centre of France, if you go to see a farmer who breed a sales and say, OK, you will have cows without horns. I think that you need to run fast. OK.

And regarding genetic selection, you have the problem that you have a limited number of boots at the moment. But anyway, it's a possibility. Then you need to substitute and we know that for instance that the cauterization before one month with analgesia is really less painful.

If we compare, for instance, with caustic paste that you can apply on the horn, we know that it's very detrimental, especially in terms of chronic pain. OK, so really avoid caustic paste. And why is it recommended to make Dehorning before one month rather than an older animal because just if you compare here the anatomy here of a young calves below one month, you can see here that the quantity of tissue that we need to remove is really less so inflammation will be less, so pain will be less, OK?

And if you wait. Above 2 months, for instance. First, you can have some risk of infection and sinusitis, for instance, of infection.

And for sure, the part of the horn that you will need to remove will be even larger, OK. And sometimes, even with a cauterization, it will not be enough and you will need to make a knife or to make surgery, etc. It will be bloody and it will be very painful for the calf, OK?

So, substitute, move from caustic past to themicoterization to thermicoterization on all the calf to younger calf. And last but not least, treat pain through pain by using NSAIDs just before the dehorne, by combining NSAIDs with anaesthesia of the of the corneal nerve, for instance, and adapt it to for sure to the procedure and and reevaluate it so. In, in that context, NSAIDs are really pivotal.

OK. And when I talk about multimodal analgesia, I just give you, put you on that picture, the different kind of action of the different, I would say analgesic drugs that you can use. So, an anaesthetic ones such as ketamine oxylazine, so alpha 2 agonist, but also look at anaesthetic and NSAIDs.

OK. So for sure, NSAIDs, as I told you before. They will decrease the inflammatory soup at the local site of the problem.

So for instance, if you have laus here, for sure it will reduce the inflammatory process, reduce the nociception, but you have also a central effect here by decreasing the, the central sensitization. Pain. So just keep in mind that NSAIDs have an effect not only locally here, but also on the central nervous system, OK?

And it's especially important to use NSAIDs in the very early process to avoid the installation of hyper agesia and allodymia. OK. And regarding the adaptation of pain treatment, according to the, to the level of pain.

So here I'll just give you some example of what we can consider as Liver one painful condition, level 2 and level 3. OK, so it's just a proposal that we can have a discussion in that, but here we can quote for instance, pneumonia, onalitis, lameness, OK. And then probably NSAID should be the first line treatment and it can be done by the staff, by the farmer, by the technicians.

You have some more painful procedure or conditions such as, for instance, sometimes trimming, castration, dehorning, C-section, and in that case, you need really to combine NSAIDs and local anaesthetics, so probably you need a combination of maybe the first line treatment by the farmer and then the vet came and in addition, you. You make some anaesthesia and for sure if you have little 3, a painful conditions such as, for instance, a ride this based mere amputation. So here clearly, the farmer cannot treat pain alone.

You really need to call the vets in order you to combine all the different combinations that we, we thought before, OK? So, considering this, 3S approach, I would like to, to know guys, with the last pole in your activity, which type of intervention, should deserve a 3S approach as a priority? What you can see as a modification in your practise, dehorning, castration, mastitis, or a C-section?

At the moment for you, which one needs to be very reconciled? And yes, also Rafae if you can after the pool and so also this question that has been asked regarding what what is the Among the non-steroidal product, which one better relieve pain? No problem.

I will, I will ask you just after the pool. No problem. Thank you.

No problem. OK, so the horning and C-section, so exactly the same that that in France, in France, I think treating pain, facing mastitis, especially toxinic mastitis is more, I think it's a mode. But for a clinical mastitis, it's not so frequent.

Antibiotics are the rules, but adding NSAIDs is not so familiar despite we know that it improves the fertility of the cows and the cause suffering from mastitis are very frequently a decrease fertility, and we know that adding NSAIDs in addition to the antibiotic will increase fertility. But this is exactly the same in France, dehorning in C-section. Dehorning usually the, I would say the only analgesic treatment is a rope to really restrain the cow or the calf, sorry, but not so much anaesthetic and even more NSAIDs.

And for C-section, it's the same C-section, we have local anaesthetic, but it's not so frequent to make, to make NSAIDs. And so to answer to the question, among the different NSAIDs. Is there anyone better than another one to, to treat pain?

To the best of my knowledge at the moment, we do not really have strong data to support one NSAID rather than another one in terms of, of pain management. I think we are lucky enough to have a lot of very good NSAIDs, fluexin, meloxicam, ketoprofen, so, carprofen, we have really a lot of, of, of, of good NSAIDs, and I would say that that's at least my opinion. I would be happy to share that with you.

No matter which one you do. If you do NSAIDs, it's already good for pain management. But then you have additional things that you can take into consideration, depending if you are treating beef or dairy cattle, depending on the duration of action, depending on the way of treating animal, injection, you have some product that you can put on transdermal, approach.

You can have also the withdrawal time, which is pretty different depending on, on, on the, on the product. So I would say. The, the, the, the, the criteria that could maybe you to prefer, could lead you to prefer one NSAID to another one is probably not linked to the analgesic effect, but rather than maybe antipyrexia, we know that for instance, ketorofen is really, very good to, to, to, to treat pyrexia, OK?

Or maybe the, the easy of use, but to the best of my knowledge in terms of pain management, there is no really data to support the use of one rather than. OK, so now we move to the last part of the presentation before taking the floor to, giving the floor to look. So, about the use of NSAIDs and pain management, OK.

So, I, I try to give you some example on, on three very important, diseases, to my opinion, so reproductive disorders, lameness and, and, . Also, BRD of respiratory disorders, but just before that, and it's also another way to answer to the question of for a few minutes ago about the cost of pain. I think the idea is first to know what is really the impact of a disease.

Very frequently we talk about the cost of a disease, but I think it's more correct to talk about the economic impact because the economic impact is divided into two parts, the costs and the losses. And what is very easy to see from the farmer perspective is the cost because the cost is the money that you spend to pay the vet, to pay the medicine, to pay the disinfectant, or you pay for something, so it's really a cost. But what is not so visible, and that's and that's a pity because it's even more, it's 2 times more than the cost and usually we consider that the economic impact of the disease is 2/3 of losses and 1/3 of cost.

And what is the losses, losses is money that should be in the in the pen of the farmer and disappear. OK. And so for the farmer for sure, as it is money that he did not receive, it's not very easy to To assess, OK.

So what we propose if we move from a situation where you never did NA to a situation where you do NA systematically or frequently for sure, we can't lie to the farmer. It will increase a bit the cost so the cost of the treatment will be a bit higher. OK.

But not so much because NSAIDs is not the most expensive treatment. But what you can expect is a decrease of the losses so that the combination of both decrease the losses maybe an extra cost that can lead to a benefit. And so what I will try to show you afterwards is what is the amplitude, what is the intensity of the decrease of losses that you can expect after treating pain, OK?

So here, I give you an example of a grid. So this is the, the link that I put on the chat, and if you go on the link of a society that delivers some minerals, which is Zim Z E N P R O. OK, you have the possibility to upload a grid in in different languages Spanish, English, etc.

OK. And so interestingly, using this grid, some researcher looked at the relationship between the intensity of LS from 1 to 4 and 5. And the impact in terms of dry matter intake, milk yield, and also fertility, corresponding here to the day's open.

OK. And as you can see here, even with moderate lameness, you have already a decrease in milk yield 5% and 5% on an entire lactation. Believe me that it's, it's a lot of money, OK?

If we increase the level of lameS3 and even ER 4, you can see that you have a stronger decrease on the milk yield up to 70%, so it. More or less, it's like if the farmer does not milk the cow for 1 or 2 days per week, so it's really huge. And here the risk of cutting, which is really increased, and you can see here the milk yield, which is reduced by 1/3.

OK. So clearly you have a very strong economic impact and what I, I want that you keep in mind, even for very moderate moderateness. And I don't know the situation in your country, but at least in France, when you are discussing with farmers that are treating pains and especially lame cows.

You ask to the farmer, how many lame cows do you have? They, they talk about this one, the number 4, but not number 2 and 3. OK.

This is why when you see 30 or 40% of lame cows, the farmer just see maybe 5 or 10%. OK. And when you look at the distribution of the economic impact of lameness here, this is a result of Kosabati in 87, in 97.

OK. Here you have the distribution of the cost, impact cost of lameness and as you can see here, OK, the veterinarian accounts for less than 10%, OK. The vast majority of the economic impact is the loss of fertility and the increased risk of culling.

It's approximately 60% of the impact and we consider that as a rule of thumb, a case of lameness as a mean is between 350 and €400. OK. So just hear some information about the economic impact of Flamenessa.

I will not spend too much time here, but just to give you some some information about the, the, the, the real impact on that, so you can see a real impact in terms of production for sure on milk. Both at long term but also without whole lactation and pressure on reproduction and. So no, when you look at the lameness, I would like to know on your daily practise in case of lameness, do you use or the farmer use NAs, always, often, sometimes rarely or never.

OK. OK, and I see some question on the chart that I will, I will answer. I see one question on the side on the, one question on the chat on the side effect of NSAIDs.

I told, in the introduction part that to the best of my knowledge, when you look at the pharmacovigilance report, you don't have so much side effect. I think the, the main risk is to, to make repeated injection, for instance, over 2 or 3 weeks, but to, I think it's something which is really scarce. Usually you make 1 or 2 injections ready to train as early as possible pain.

So if you don't do repeated things normally it's not a problem, OK? And I think that you, there is another question on the chat. Oops.

And the Q and A if I can open it. About NSAIDs for food producing animal and withdrawal is also important, yes, so you're right, for sure. Withdrawal time either for milk or, or, or for meat is something important to take into consideration, but if you have a cow which is painful, for instance, obviously lame, etc.

Or affecting by your condition normally. If the cow go at the slaughterhouse, probably that at the press slaughter examination, the cow will probably not go through the examination until the end. So I think it's really good to, to treat the cow entirely, especially for pain before sending him to the slaughterhouse, but you're right, when choosing an NSAID, the withdrawal time both for milk and, and, and, and meat should be taken into account.

Absolutely. So happy to see that very often NSAIDs are used, so it's really good news guy, and, and sometimes in 31%, but it means that in, in, in, in the, in some cases, probably you, there, there is still room for improvement, but when you combine always and often it's really good, really impressive. OK.

And why NAs are really important to trade claimness because if you look at the different kind of affection that can occur on the feet. Either infectious or, or, or, or not infectious ones, so laminitis, so ulcer, etc. To DD and inital dermatitis.

You can see that they all have an inflammation components. Not all of them have an infectious component, but all of them are driven by inflammation and a lot of them are associated to swelling. So NSAIDs are really pivotal and when you look at the, at the study, so here are first one, they need to know if whether or not NSAIDs are effective, when combined.

To trimming, OK, so they looked at more than 60 cows receiving a saline or renixin, OK, before trimming and some of them receive saline before shadow trimming just to have the impact and the stress, but not the pain of the trimming, OK? And they, they observed the. Lying time, OK.

And they observed an impact, a bad impact on lying time shorter for the animal which were treated, better get scoring, better movement, and more visit at the feed bunks. So probably more visits at the feed bunks, it will lead to a better milky for sure. OK, so clinical improvement for lameness with the use of NSAIDs, no problems, OK.

When you look at the lameness in, in robot system, the interest that you can follow and monitor, continuously the milk production. And when you compare treated and non-treated animals, OK, at least reaming and blood more or less and, you can see here an increase on the milk yield of 0.1 to 0.3 kilogrammes of milk per hour.

And when you add all this this increase by all the cows within one herd, etc. It makes a lot of milk at the end of the day. OK.

And last but not least, I think it's really the most important thing to, to, to keep in mind when you, you want to treat lameness. This is the earlines of the treatment. OK.

So here, these are the results from colleagues from Nottingham University. They compared free way of treating the animals. So here, cows suffering from lameness due to lone horn lesion, OK.

So white line disease, so ulcers and things like that. OK. And they compare trimming alone, trimming plus block, trimming plus ketorofen, and trimming plus plus ketorofen.

And as you can see here. In case of early treatment, early treatment is treated as soon as the lameness is detected. You can see that the percentage of cure are really good, OK, from good to really good.

And the best one was for sure the combination of trimming block and ketorofen because once again, inflammation is a key process not only for digital dermatitis, but also for chlorova. But when the treatment was too late, late was approximately 3 weeks to 1 month after the occurrence of the lameness, you can see here that whatever you will do, it will never, it will never success. OK.

So the key to treat lameness is to treat as early as possible and by using NSAIDs in addition to the classical training methods. And beyond that, for sure, nothing the cowa isolation for sure will help to improve recovery. So nursing is really crucial.

So now, if we move to reproduction before ending by body respiratory disorders, I would like to know if during a C-section or a dystopia or prolonged scaling, do you use or the farmer and say, as always, often, sometimes rarely or never. So We will open the pool. And you will be able to answer.

OK, so we'll be able to see the reasons now. So always, once again, 37%, so very good, often 35%, sometimes, etc. So the situation is better than in France, huh?

It's very good. OK. And from a broader perspective, so for sure for C-section, it can be beneficial.

The only side effect that you can expect is due to the fact that NSAIDs act by inhibating prostaglandin synthesis, then you can have an increased risk of retained plansatta. So you just need to be careful on that after C-section. That's the only, I would say side effect that you can expect of using NAID after calde or C-section.

But regarding metritis, I would like to share with you this interesting study conducted in Greece where they compared the interest of doing or not NSAI in case of prepar metritis, but also endometritis. OK, so they look at the impact of longevity, but also fertility, OK. And as you can see here on the results on the next slide here, you have the group treated with enexine or the group treated with placebo knowing that all the animals will receive antibiotics for sure.

OK. You can see she has 60 days, 75, and 90 days postpartum, the cows with complete uterine evolution and here the base open. And as you can see here, the results were already better both in terms of complete uterine evolution but also in terms of base open on the cows treaties with NSAIDs.

OK. One of the difficulties when looking at the effect of NSAIDs on reproductive disorders is that systematic use of NSAIDs will lead probably to see nothing. Because you will add and you will treat cows.

Remember, the blue one and the red one. The blue one we will cope with inflammation will probably have no benefit from insight, but the red one, yes. So what you need to really carefully look at, especially if you do a reproduction monitoring, frequent monitoring of the cows after calving, is to look at the cow with chronic metritis, endometritis.

You can be sure that this one will be benefit from NSAIDs, OK? Another interesting study, more recent, this one conducted in Switzerland, they do the assumption that if they treat early the metritis only with anti-inflammatory drugs, it could lead to decrease the use of antibiotics. We all know the context of the need to reduce and rationalise the use of antibiotics.

So here they decided when they detect a peripheral metritis, either to give only in addition to free therapy, only ketorophan or safetophir, and if after injection of ketorophenolone, the, the clinical care was not good. Clinical cure to give a safe here. So here you can see the number of what they call extended treatments.

So for sure, the number of treatment that they need to give in addition to the ketorofen was higher. OK. So it means that the cow receiving antibiotic at the beginning.

They do not need extra treatment rather than more or less than the other ones. But when at the end of the day you calculate the number of doses, you can see that the number of doses in the group ketorofen was 50% lower than in the group receiving er. So I think that at the moment it's probably not ready to, to use only in an anti-inflammatory drugs, sorry.

Alone without antibiotics, but probably in the next years, I think we will be able probably this fully test to be very early in the detection process, and then maybe just giving anti-inflammatory drugs at the beginning can be one of the solutions. OK. And now, if we move to the last part of the presentation regarding BRD respiratory disorders, OK.

Do you use, once again and say always, often, sometimes rare or neck, OK. It will be the last call of the presentation. But for the moment, I see that the, the procedure that you do on the daily practise are daily basis are really very good.

Congrats So maybe we can see the results now. OK, once again, often and always really good, but maybe rarely 10% or so, maybe 25% of cases when we can maybe still find a room for improvement. OK.

So then what can I share you as a results by using by the, about the use of of NA. So here this study conducted in the UK, OK. So they, they make a random study, OK, either by using safetufuolone or cephe plus fuixin, OK.

So safetu or er plus fuitin, sorry. OK, among young girls, OK, with hypothermia and respiratory disorders. So they look at the decrease of temperature.

So not surprisingly, the group of of cattle receiving both Four and honixin had earlier and stronger reduction of temperature. Sure, makes sense. But when you look at, at the, at the, at the necropsy or at the slaughterhouse, they make a, a, a scouring lesion of the lung, especially what they call the, the, the, the density along scar or the more firm, the, the, the, the the the.

The lung is the, the worst is it? Because when the lung is firm, it means that it is not very functional. You do not have a good oxygenation and usually it's associated with bad daily weight gain.

And as you can see here, the mean of the of the scar. Was really lower, both in mid and median for the cow or the calf receiving both reexine and cer it means that in terms of lung lesion, it's good to, to add NSAIDs to antibiotics, OK. And last but not least, when you compare on that study, OK, the the concomitancy between hyperthermia, this is a curve.

OK, and the treatment, antibiotic treatment done by the farmer, these are the bars, OK. So here the temperature of the animal was monitored by criminal bos that order to detect the the hyperthermia on, on a real-time basis, OK? You can see that hypothermia is a very good criteria to detect a BRD, OK.

And when at the end of the fattening period we compare. We took at the reference, the, the, the, the bones with absolutely no hyperthermia over the fattening period, OK? But when you look at the, at the animals just with hyperthermia but without any further treatment by the farmers, so maybe cow calf that do not show too much clinical signs or missed by the farmer, I don't know, but at least you can see that over this one, you already have a decrease of the daily weight gain, OK, 30 grammes per day.

When you compare the the calf, not suffering from hypothermia to lose, we received one treatment for BID by the farmer. You can see here the daily weight gain decreased even more. 2 treatments, 3 treatments, the more they treat the animal, the more the impact was on the daily weight gain.

But it means that hyperthermia alone, without even very strong clinical sign can be detrimental for daily weight gain. So it means that Adding NSAIDs to the classical anti-infective antimicrobial therapy is a, is a worth of use for treating B, OK? So to conclude, and then I will give the floor to Luke and I will ask maybe to some questions if you have any, I will be happy to answer.

I hope that I convince you that pain do exist and deserve to be treated, but as, as far as I see from the poll, your, your practise is really already very good, OK? NAID is really a treatment of choice. To improve the clinical, state of the animal, the clinical sciences, to reduce the, the impact of in terms of performance, impact of performance, milky, killing, fertility, fertility is very important.

Improved welfare, we know that inflammation and especially chronic inflammation is very detrimental for fertility, and we know that now fertility is really something very sensitive for the economy of the, of the farm. OK, and it should be really considered as a first line treatment by the farmer. And to, to do that, maybe to promote the, the freest approach.

So remember, suppress, substitute and so. I think that as a vet, we have a key role to play for pain management and for welfare, more generally and especially a role to promote the, the, the knowledge of farmers on pain detection and management. So, once again, thank you for the invitation.

Thank you for your attention. Thank you for participation, and I would be happy to take some questions. Thanks a lot, Rafael.

So yes, please do, if you have any questions that come, . You can ask them now or you can still write them in the Q&A when Luke will be talking. They are shy, still shy.

But yeah, OK, so Luke will start now with the presentation. Well, I think, can you hear me? Yes, but please can you share my screen.

That's OK. Perfect. Thank you, thank you very much, Audrey, for the invitation and thank you very much, Professor Guio for your, your lectures was brilliant, really, really brilliant.

And leukaemia, because you cover some aspect of my presentation, I can't go faster, but, what I would like to, to, to, to talk, . Within the next 15 minutes is about a solution we have a solution we promote in terms of control of pain and inflammation in cattle through medicine, which name is Crasedu. And of course, you already presented this and I don't want to spend too much too much time on this, but the aspect of the inflammation, we all know this, we all learn this at the university, about the key aspect of of inflammation.

We use the, in our reflection and also metrics and you, you presented Professor Gutte all the, the clinical examination of the, the, the animal suffering from pain, with, facial expression, with the gait, with different things. And, of course, you said that there are also more scientific method to assess pain in Animals and we used to talk about aperalgesia, meaning the measurement of pain and how the perception of pain by the animal that suffer from pain, is, percept. And, I think you have to imagine that when an animal is exposed to painful stimulus, of course, it's at the beginning.

The stimulus is low, is, OK, can't bear this. There is a, a limited reaction, of course, and then it dramatically increase, because, it's too painful, so, so the animal reacts on the, on this. But if this stimulation, this painful stimulation, what we call the noxious stimulus, being chronic, meaning that it's long, for a long period exposed to this because of the awning as you explained, or because of surgery, because of lameness, of course, .

The, the, the, the, the level from the animal reacts tend to decrease and we call this the hyperalgesia, meaning that because the animal is chronically exposed to pain, it tends to perceive pain more accurately, more fully and for sure, this change in the level. Of perception of pain, called the, the resol of hyperalgesia is an important, phenomenon that can be followed up, during studies. And this is what we did in different studies and I'm going to, to explain this later.

Of course, you also, expose this. All right. For farm animals with long term and this is why farmers use a lot of antibiotics because we have kind of chain between the infection and we have a lot of infections in animals in farm animals, inflammation and we can see the inflammation with the infection of the others and you have the infla inflammation of the other that this this is called mastitis.

And then next step is. This lesion is painful and we frequently skip the two aspects of pain and inflammation and just use antibiotics because, OK, what is the rational is to control the infection, and secondary to control inflammation and pain. The fact is that progressively come in mind the idea that Infection itself cause pain.

And we have studies from experimental animals and rats, for example, or where there's just the infection Staphylococcus, in some part of the animal, is able to increase, to decrease the threshold of, perception. Of pain, the hyperalgesia. OK.

And this is the same thing for disease of farm animals. We have mastitis, you know, we have acute or chronic mastitis. The cause is clear, the cause is bacteria or mastitis are more or less bacterial disease for sure.

And this cause inflammation and this cause pain. We know that. Pneumonia, of course.

Bacteria and virus that cause acute or chronic inflammation of the organ of lungs. But it is also cause pain. I will go back on this later.

Arthritis, same thing. I digital dermatitis caused by bacteria, but also is an infection and something painful and may try this and I get back on this data. So, most of the Condition with it conditions.

They are of course linked to distinctive infectious agent, but they are also cause algesia, meaning that you, you, you decrease the level of reaction of animals to a painful stimulus. Well, just want to go fast on the three aspects of particular importance in cattle as a respiratory disease, of course, because, it's probably the most important disease in cattle worldwide, affecting both young animals and calf, and this is a major factor of calf morbidity and, also mortality. And the main cause, of course.

Of antimicrobial use, these animals or for individual treatment or for metaphylaxis, which is a form of collective treatment with antimicrobial and But we have a low incidence in adult cattle and particularly in adult dairy cattle, but it couldn't, it's a cause of mortality in adult cattle. Cause of mortality directly or cause of mortality because of the infection at a young age. And it could represent more than 10% up to 50% of fatalities in adult dairy cattle and also.

During the transition period, as explained by Professor Guti, you know, the, the two curves, the blue, the blue one and the red one just after carving, this is at this stage, it's very important that and significant at this stage and This causes an increased use of antibiotics. An interesting point is what is presented in this graph on the right side of my slide. It's just a report about the research made on calves, that were a challenge with, is to someness if I remember well, a group of animals were infected artificially, with hisophilossoms, and of course some of them developed.

Pneumonia and some of them not. And, those who developed the pneumonia, is this blue line, the measurement of the nacipi resol, meaning that the level beyond which they react, tend to decline compared to animals that remain healthy. And the effective resol was just measured by just squeezing one of the limbs, with a jaw or something like this, causing pain and because they were infected, the respiratory tract was infected.

They perceive better, I can't say this, they perceive more pain and painful stimulus by the just the fact of the decrease of necessive result. So we have this phenomena in pneumo pneumonia and respiratory infections, and this is why the control of pain through disease, is of particular importance for this disease. Other aspect of course is nameless in cattle.

We all know that it's painful. It is very common and as Rafael explained before, the producers they just see the, the, the, the, the tip of the iceberg. Of course, most of the animals, lame lame animals, they are not detected or they are detected but they are not considered because just yes, small legend, little.

Of course, this is, this is a MO, but that's severe than this one. This one is a NO. So it's a matter of perception of the, of the disease.

And of course, most of them they are treated with NSAIDs as we see, you use a lot of NSAIDs of sis, but also antibiotics because of course we know that we are part of this. Lesions caused by different things at different place of the, of, of the, of the food, between the claws or above the claws but infectious are caused by, by some bacteria. And of course it cause cause a big impact on productivity.

in this study made also, in the UK, some years ago, they just use ketorofen, on lame cattle. And the, on the left side of the graph, you have a group of animals treated with just saline, just injection of saline serum. And on the right side was ketorofen, 3 milligrammes per kilogramme for 3 days, OK?

And The researchers in the in this work, they measured the narcisceptive threshold and you can see you have different metrics. This is Newton this meaning that we, they applied force on the limb of animals and they just look at the reaction of the animals and for animals treated with just with saline, the noisceptive result was lower. Than it was with animals treated with kerofen and it was treated with ketorofen.

Not only the narcisive threshold was higher, but tend to improve or improve or being higher progressively over 1 month after the treatment of 3 days. Meaning that the early treatment with schitorofen and said for just 3 days have a long lasting impact on the improvement of the perception of pain. This is why it is important to treat early and to treat, to treat animals with lameness with with NAID and control pain.

last aspect among the all the disease that can affect cows around calving and we said some word about pneumonia and about mastitis is of course metritis. An interesting research from Stoykov and others in 2015. It was about the the gynecologic examination of a, of a cow, dairy cow, just after calving.

It's a very common procedure for, for us vets, and the exam consists in the external palpation of the uterus, through the, through the rectum. It's relatively easy. We have all learned how to do this and the fact that If you compare the reaction from LCO or cow with a normal involution of the uterus or a cow with a metritis or an inflammation of the uterus.

And they look at this, they look at the back line of the animal and When the, the technician of the vet slide his harm into the cow, of course, the backline arch and the arch is bigger because of the inflammation and the pain caused by the metritis. So the conclusion is the difference was significant between causes affected by metritis and cows free of meteoritis, and the conclusion that meritis is paid for. Well, We have a solution to this dilemma of as presented by Rafael about this study, by Paul and and his colleagues.

Should I use ketoprofen for 2 or 3 days, then use antibiotics if The treatment failed or the success was not what was expected. So I increased the number of days treated. Or should I treat first with antibiotics and we, we, we, we saw that we succeed.

And of course, something raise in our mind to combine both ingredients antibiotics in one hand and get arofen instead on the other hand, and particularly for dairy cows because we saw that we have a lot of, condition that, that we have this kind of treatment and . So we developed a product called Curraduo, which is a combination of ketophil on the one hand and ketorofen on the other hand. Weta dosage of 1 mL for 50 kilogrammes body weight intramuscular once a day.

And because someone asked the question, of course, microzole period 0. Zero hour because capture the maximum residue level is very high, so we never reach the level of residue or harmful residue and the ketofen. There is no maximum residue level because it is a special category of medicines.

So, it can be used on there and there it goes with no milk withdrawal period. Well, of course, we tested this on respiratory disease because it's a very common situation, particularly on young animals, and we found out that in a group of animals treated. Calves, maybe 4 to 6 months old, treated all with ketofu alone ready to use keto or keto plus ketorofen, curracevro.

Finally, the success rate was significantly higher in animal treated with ketrofu and ketorofen, and they were treated. At the beginning of the disease because, they were under scrutiny in some farms. It was both in France and Germany.

So on the first, sign of disease they were treated and succeed on this. And also, if you can just compare the success rate in terms of control of pastorella mutosida or manemiamolitica, results were better in animal treated with plusketorofen compared to animal. With your alone, of course, the difference is not significant, but the fact is from the clinical point of view, we clearly improve the, the, the success, success rate of the, of the treatment in combining the NSAID and the antibiotic.

We did the same thing for, cows with, digital flagment, food rots. And the dairy cows were traded, see almost 180 dairy cows. And of course, success rate was Better in the ketorofen treated animals treated racid compared to animal treated with k alone and the clinical success, of course, takes some time.

It improved, but it improved slowly. Just to remind you that in most of the European countries, I mean, countries of the European Union, this is, not allowed to use residue for this indication, because of the restriction of use of of fuel. And, of course, because, this product is also viable in many countries around the world and where the, the regulation is not that strict that, than the regulation we have in Europe, we tested this, in propable metritis in Mexico.

And we finally demonstrated that we compare two groups because, in most of countries because it is based on, Research made two decades ago or more at the time, . Pfizer or even before, a John marketed, they tested a dosage of 2 milligrammes per kilogramme body weight or even more for the control of metritis and, this turned into a kind of bad habit, in many countries and particularly in Latin America. So, farmers are used to, to inject kef your fuel based on the 5% solutions of keto fuel.

At the dosage, rate of 2 milligrammes per kilogramme body weight for 3 to 5 days depending on the, the, the, the clinical size of the healthy animal. We concurrently use a cursive du at the standard dosage for k of 1 milligramme of keto plus 3 milligrammes of ketoprofen. And we finally demonstrated that we have the same results.

It's not inferior to the standard treatment. But we use as the dose of antibiotics just by combining the ketuprofen, OK? The same thing for dairy cows affected by initially we were supposed to use in Italy, Cura duo for different conditions of the dairy cow, in level condition, respiratory disease.

The fact is that after most 18 months of observation in Free herbs. We had mainly metritis, of course, with Pyrexia, and the researchers of the University of Palma, they use residual and finally found that, cows with metritis treated with cursive drug compared to cows with meritis treated with a standard keto, of course. The success rate for the first artificial insemination was better in this group, treated with curse and was almost similar to the research we had with healthy animals without metritis.

And the same thing for the pregnancy rate, within the 1st 120 days in milk. Meaning that As previously explained by Professor Guo, for sure, the combination of ketorofen and K2O probably has a positive impact on the, on the, the, the, the, the healing of the disease of metritis. Just to remind you that in the EU can you first consider a cat, a category B antibiotics.

Meaning that You should identify the bacteria susceptible to keto fur. You don't have any other option to use this, this antibiotics. And if there is no alternative on the market in categories C or D of antimicrobials, but the fact is that it works really.

And the combination of keto and ketorophan works good on very common disease such as borespiratory disease, every infection of the, of the food, particularly food rot and meorritis. And I think that it's my last slide, for, so for sure, the treatment of infection and inflammation simultaneously may contribute to control pain in animals infected by painful conditions. And then for sure it's a positive impact on animal welfare.

The combination of keto at this dosage, 1 milligramme per kilogramme, and ketorofen, 3 milligrammes per kilogramme. Increase, of course, convenience, observance, and result come faster. For this kind of disease and pay attention to this mention off-label use.

Depending on the country you are, OK? So, we consider that the combination of the two active helps to improve animal welfare. And I would be happy to have your questions.

Thank you very much for your attention. Thank you very much. Look, actually there is one question.

For how long should we use curraduo? Only 3 days? How about ketoprofen if we use it longer?

I'm worried about gastrointestinal bleeding and ulcer. This is an excellent question and I thank you very much for asking. Actually, in the research we made, we use Cursiveri for.

23 days. And depending on the evolution in the clinical situation, we switched for Ke your you alone. If the improvement was good, particularly for respiratory disease, .

If after 3 days treatment with ketorofen and Keto, the calf with better, no temperature, improvement in the, in the food intake. We just stopped kerase and we moved to Ketophilolone. And we did the same for lame cows.

But we also tested the product for 5 days at 3 times the dosage, and we didn't observe any bad . The outcome. And then yeah, the question is if it's 23 days, how about antimicrobial resistance and in fact, yeah, because we always recommend to use antibiotics for 3 days, but as you say, we should treat after to to to do at least 3 days of the.

Antibiotic treatment, right? I'm not a specialist in, antimicrobial therapy, but for sure, all what we learned in the past about treat fast, long, and, at the right dosage, right dosage for sure. It's correct.

But, it's not sure that, long treatment do not contribute to development of resistance, maybe short treatment. Do not does not contribute, but continues or exposure to antimicrobial for several days as a probably a detrimental effect on the selection of resistance. So, probably we can make a general rule, it could be related to the antimicrobial itself.

Mm, yeah, it's depending on the antibiotic. Yeah, it's complicated. Yeah, it's not an easy topic.

Another question is, you mentioned, so is a category B and what means CND antibiotic. See men cautious and the prudence. In the D category, you have all what we call the old antibiotics tetracycline, for example, and in C you have macrolite.

This kind of antibiotics, the modern microli we have for the, the control of respiratory disease, long acting microlites are category C. Category B is, you have some real constraints on this. The objective is not to use.

Objective is you use them when you don't have, an acceptable solution, technical, . To some extent economical, but the first technical. OK.

OK. Any last question? It helps again, mycoplasma mastitis, what do you mean?

I would say certainly not. No, me too, but no, forget it. In fact, that's why we didn't present any any use on mass, so there was no, I'm very stuck on this because it's a question we are frequently, from the existing literature.

Cur is not a good injectable kur and not a good treatment for mastitis. Local, infusion of kur is certainly a good treatment. But injection is not, and we have a lot of publication on this, probably the, the, the absorption, from the General compartment load, and, to buy the other is very low.

So the concentration at the end of the day in the hood are very low and not not active against most of the pathogens. OK. Cause I don't see any other question and So I think we can wrap up.

Thanks to, to you too for your great presentation. Of course, if you still have questions that come after, contact your local your local people and, and, please send us a question after that and we will answer, of course, all your questions, so. That's it.

Thank you very much. Have a good, have a good evening and bye-bye. Thank you very much.

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