<p>Lameness has a large negative economic impact and it has been estimated to cost the U.S. swine ~$23 million/year. Science-based guidance for the industry on optimal housing, management and treatment of lame pigs is deficient. There are no approved drug treatments for analgesia or lameness in swine and, the identification and validation of robust, repeatable pain measurements is fundamental for the development of effective analgesic drug regimens and management strategies. Our proposal presents original preliminary data demonstrating the feasibility of inducing lameness in pigs using a chemical model of synovitis and concurrently measuring stages of lameness in the same pig using a variety of detection tools that span (1) kinematics (2) physiology (3) pain and (4) behavior. Our specific aims are to: </p>
<p>(1) Use an innovative chemical model of synovitis to create populations of pigs that are experiencing pain manifested as lameness and validate a list of objective assessment tools. </p>
<p>(2) Utilize tools to quantify the analgesic effect of two non-steroidal anti-inflammatory (NSAID) drugs using the chemical synovitis model. </p>
<p>(3) Utilize the most effective NSAID to quantify pig preference for bedding when experiencing pain through the manifested of lameness.</p>
<p>NON-TECHNICAL SUMMARY: <br/>Lameness in swine has a significant impact on animal welfare. The results of a recent survey conducted by our research group indicate that 84% of sows at slaughter had one or more foot lesion. Further analyses identified that over 20% of sows are misclassified by farm caretakers as to why the sows leave the herd prematurely and gilts and sows exiting the breeding herd prior to paying for their economic inputs result in a net monetary loss for the farm. It has been noted that by improving longevity by .10 (moving from an average parity at culling from 3.4 to 4.4) is worth ~$23 million/year to the U.S. pork industry Lameness is therefore considered one of the most important causes of culling in sows in the United States and is a significant animal welfare issue. Science-based guidance for the industry on optimal housing, management and treatment
of lame pigs is deficient. There are no approved drug treatments for analgesia or lameness in swine because identification and validation of robust, repeatable pain measurements is fundamental for the development of effective analgesic drug regimens and management strategies for use in lame pigs. Research to address the limited knowledge in this area is essential to formulating science-based recommendations for pig producers. This will become especially important if legislative actions succeed in preventing downed animals from entering the human food chain (Prevention of Farm Animal Cruelty Act and the Healthy School Meals Act) regardless of etiology. This proposal develops detection tools, objective decision criteria, and validated treatment regimens to prevent lame and painful swine from entering the U.S. food chain and compromising food safety and public acceptance.
<p>APPROACH: <br/>Specific Aim 1 will use a chemical model of synovitis to create populations of animals that are experiencing pain manifested as lameness and validate a list of objective assessment tools to determine which of those tools discriminate between animals in a painful and non-painful state. A total of 24 non-bred pigs will be allocated to treatments (left rear [n = 12] or right rear hoof [n = 12) and acclimated for 7 days prior to study commencement. Each pig will serve as its own control and treatment in a cross-over design. Pigs will then be placed onto trial and kinematic, physiology, behavior, health, performance and pain sensitivity measures will be collected the day before induction of lameness (D0; baseline), the day after induction (D2; most lame) and 7 days after induction of lameness (D8; recovery and resolution of lameness). Specific Aim 2 will
utilize the tools identified in Specific Aim 1 to quantify the analgesic effect of two non-steroidal anti-inflammatory drugs (NSAIDs), flunixin-meglumine and meloxicam using the chemical synovitis model. A typical pharmacokinetic study will be conducted for each of the potential analgesic candidates. A total of 24 non-bred pigs will be used for each drug in a two way crossover design. Six pigs will be randomly allocated to each of two routes of drug administration: Meloxicam orally and intravenous or Flunixin-meglumine orally and intramuscular. Serum samples will be obtained and assayed for the target analyte. Next pharmacokinetic parameters to design a dosing regimen and route of administration for these two drugs (n = 12 pigs/drug/appropriate route) will occur. Specific Aim 3 will utilize the most effective NSAID from Specific Aim 2 to quantify pig preference for bedding when
experiencing pain through the manifested of lameness. A total of 36 clinically normal, non-bred pigs will be allocated to one of two treatments; trt 1 NSAID identified by SA2 or trt 2 nothing (control). On D0 (baseline) two types of flooring will be offered to the pig (1) concrete floor and (2) corn stalks. Activity, behavior and health measures will be collected the day before induction of lameness (baseline), the day after induction (D2; most lame) and for 7 consecutive days after induction of lameness (D3 to D8; recovery and resolution of lameness). Data Analysis Repeated measures data (blood, behavior, performance, pressure algometer, plantar, GAITFour and embedded microcomputer based force plate system) will be analyzed using a Mixed Effects model allowing for unequal variances across time (PROC MIXED, SAS). The model will be fit with treatment group, time and treatment by time
interaction as fixed terms, and animal as a random effect. In addition, comparisons will be made between pre- and post-lameness measurements using a General Linear Model (Proc GLM) with non-bred pig age in days as a covariate. Non-compartmental analysis (based on statistical moment theory) of the Flunixin-meglumine, and Meloxicam time-concentration data will be performed using the commercially available software program WinNonlin.
<p>PROGRESS: 2013/04 TO 2014/04<br/>Target Audience: U.S. swine industry (National Pork Board and State Associations) Academics Welfare groups American Veterinary Medical Association American Association of Swine Veterinarians Food and Drugs Administration Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? One graduate student (Caroline Mohling) completed her Masters in Physiology in December 2013. In addition, one graduate student (Monique Pairis-Garcia) will complete her PhD in Physiology in May 2014. The title of her dissertation will be ï¿½Advancing techniques to promote the welfare of sows utilized in laboratory based lameness models. To assist on the data collection, three Animal Science undergraduates are employed to work on the research project. How have the results been
disseminated to communities of interest? Methods and results have been disseminated through peer review abstracts and papers and extension venues, for example Animal Industry Reports and trade magazines. What do you plan to do during the next reporting period to accomplish the goals? Several peer review manuscripts are being reviewed and or will be submitted over 2014. Mohling, C., A. Johnson, J. Coetzee, L. Karriker, K. Stalder, C. Abell, H. Tyler and S. Millman. 2014. Mechanical and thermal nociception as objective tools to measure painful and non-painful lameness states in multiparous sows. To be submitted to the Journal of Animal Science. Mohling, C., A. Johnson, J. Coetzee, L. Karriker, K. Stalder, C. Abell, H. Tyler and S. Millman. 2014. Kinematics as objective tools to measure painful and non-painful lameness states in multiparous sows. To be submitted to Livestock Science.
Parsons, B., A. K. Johnson, C. Mohling, M. D. Pairis-Garcia, .L. A. Karriker, J.F. Coetzee, K.J. Stalder and S. T. Millman. 2014. Behavior as an objective tool to measure painful and non-painful lameness states in multiparous sows. To be submitted to Applied Animal Behaviour Science. Coetzee, J., A. K. Johnson, C. Mohling, M. D. Pairis-Garcia, K.J. Stalder S. T. Millman and L. A. Karriker. 2014. Cortisol and Substance P as objective tools to measure painful and non-painful lameness states in multiparous sows. Submission TBD. Pairis-Garcia, M.D., S.T. Millman, L.A. Karriker, J.F. Coetzee, K.J. Stalder and A.K. Johnson,. 2013. Measuring the efficacy of flunixin meglumine and meloxicam for lame sows using nociceptive threshold tests. Review stage through the journal Animal Welfare. Pairis-Garcia, M. D., L. A. Karriker, A. K. Johnson, B. Kukanich, L. Wulf, S. Sander, S. T. Millman, K. J.
Stalder, and J. F. Coetzee. 2013. Pharmokinetics of Meloxicam in mature swine after intravenous, intramuscular and oral administration. To be submitted to BMC Veterinary Research. Pairis-Garcia, M.D., A.K. Johnson, S.T. Millman, L.A. Karriker, J.F. Coetzee and K.J. Stalder. 2014. The effects of Flunixin meglumine and Meloxicam administration on postural changes in sows induced lame. To be submitted to Applied Animal Welfare Science. Pairis-Garcia, M.D., S.T. Millman, K. J. Stalder, L.A. Karriker, J.F. Coetzee and A.K. Johnson. 2013. Flunixin meglumine and meloxicam efficacy for pain mitigation utilizing an Embedded Microcomputer based force plate system and GaitRite software in sows induced lames using a chemical synovitis model. To be submitted to the Journal of Animal Science. Coetzee, J., A. K. Johnson, C. Mohling, M. D. Pairis-Garcia, K.J. Stalder S. T. Millman and L. A. Karriker.
2014. Flunixin meglumine and meloxicam efficacy for pain mitigation utilizing cortisol and substance P in sows induced lames using a chemical synovitis model. Submission TBD. In addition the final objective to this project will be completed. For Specific Aim 3 we are using Meloxicam to quantify pig preference for bedding during convalescence from lameness. A total of 18 clinically normal, non-bred pigs will be purchased from a commercial producer in Iowa over cool. Pigs will be blocked by body weight and randomly allocated to one of two treatments; treatment 1 Meloxicam and TRT 2; control ï¿½ no NSAID. Sow behavior in their home pen before lameness induction and over the resolution period will be collected using video. In addition a pen lameness score and a walking gait score will be collected.
<p>PROGRESS: 2012/04/15 TO 2013/04/14<br/>OUTPUTS: Lameness associated with painful joint lesions has been identified as a welfare challenge for confined sows. It has been ranked as the number 3 reason for culling sows; comprising 15% of the culls marketed in the U.S. Producers in the U.S. currently treat sow lameness using husbandry tools, for example housing sows individually to provide easy access to key resources and rubber mats. Currently, producers assess sow lameness using subjective scoring systems, which have been shown to be variable in their application. Objective tools to measure sow lameness on farm are required. The objective of this study was to validate a list of potential objective tools to determine which could discriminate between sows in a painful and non-painful lameness state. Tools assessed included plasma cortisol, an embedded microcomputer force
plate system, GaitFour walkway system, thermal plantar (thermal noception) and pressure algometer (mechanical nociception). A total of 24 mixed parity sows (220.15 kg) were individually housed. All sows served as their own control and treatment. Sows were induced lame using a chemical synovitis model. After completion of the first round, sows were given a 7 day rest period and then the trial was repeated with the other rear hoof being induced lame. Three treatment days were compared (1) sound (day before induction), (2) most lame and (3) resolved (first and sixth day after injection of amphotericin B). Methods and results were disseminated through a variety of mediums; written extension materials (Animal Industry Report and National Hog Farmer) along with a poster presentation at the College of Veterinary Medicine, Iowa State University. PARTICIPANTS: Caroline Mohling, Anna
Butters-Johnson, Kenneth Stalder, Locke Karriker, Johan Coetzee and Suzanne Millman TARGET AUDIENCES: Swine veterinarians, animal scientists and the pork industry PROJECT MODIFICATIONS: Dr. J. Coetzee has moved from Kansas State to Iowa State University.
<p>PROGRESS: 2011/04/15 TO 2012/04/14<br/>OUTPUTS: Induction of lameness allows for controlled evaluation of lameness pain response in animals because pre- and post lameness measurements can be taken from the same animal. In 2009, ISU and KSU researchers adapted this model to induce lameness in sows which resolves in approximately 1 wk and built the Swine Intensive Studies Laboratory to study pain using a multi-disciplinary approach. Home pen behaviors, kinematics (while standing using a force plate developed by ISU researchers and walking using a Gait-Rite system), physiologic, performance parameters and reactions that indicate sensitivity to lameness pain can be assessed simultaneously. These tools allow a non-invasive analysis of lameness pain that can be correlated with the other diagnostic tools. Data collection on the project began July 2011 and concluded November
2011. Data collection consisted of 2 trials, 1 trial running from July to August 2011; and the other trial beginning October and running through November, 2011. In each trial 12 healthy multi-parity sows were used. Tools assessed during the two trials included: pressure algometry, plantar thermal, micro-embedded force plate, GaitRite pressure mat, behavior, substance P, and cortisol. These tools were collected over three time periods; sound, most lame and resolved. Gilts had the following measures taken on a sound (-1 baseline), most lame (+1 after induction of lameness occurred with amphotericin B) and resolved day (+6 day after the induction of lameness. All gilts served as their own control and treatment. Methods and results were disseminated through a variety of mediums; peer review abstracts in conjunction with oral presentations at state level extension meetings, regional, national
and international research meetings (American Society of Animal Science), written extension materials (final reports back to the funding agencies, Animal Industry Reports, National Hog Farmer and PORK magazine). PARTICIPANTS: Dr. Anna Butters-Johnson (PI) has oversight of the whole project. Dr. Butters-Johnson manages the budget, hired the PhD (Dr. M. Pairis) and MS student (Caroline Mohling) and both students report to her. Dr. Butters-Johnson also has a program manager report (Rebecca Parsons) to her on a weekly basis and three under graduates. Dr. Suzanne Millman (CO-PI) had over sight of the pain tests used in Objective 1 (plantar and thermal). Dr. Millman will work with Dr. Butters-Johnson on the correct analysis of these data. Dr. Kenneth Stalder (CO-PI) had oversight of the embedded force plate used in Objective 1. Dr. Stalder will work with Dr. Butters-Johnson on the correct
analysis of these data. Dr. Johann Coeztee (CO-PI) had joint oversight of the P-K studies in objective 2. He has helped direct the drugs, route and administration and helped with blood collection. Dr. Coetzee will work with the PhD student on developing a substance P bench top analysis and will also work on the blood analysis for the P-K studies. Dr. Coetzee will work with Dr. Butters-Johnson on the correct analysis of these data. Dr. Locke Karriker (CO-PI) had joint over sight of the P-K studies in objective 2. He has helped direct the drugs, route and administration and helped with blood collection. In addition Dr. Karriker trained students and the program on how to induce the transient lameness model. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Dr. J. Coetzee moved from Kansas State University to the College of Veterinary Medicine, Iowa State University.
Thermal plantar test was not completed for trial 1 (gilts 1-12) - only pressure algometry. Previous thermal plantar work did not show significant data, therefore was left out of trial 1 but decided to retry and confirm on last 12 gilts. Thermal and algometry tests were completed in the morning after data was collected for embedded force plate. Gilts were not fitted with ICE-tags during either trial. ICE-tags were not used after pilot research showed inability to securely attach the ICE-tags to the gilts. Cameras were on black and white during first trial, but color during second. Did not use lasers on thermal - lasers built for the thermal device were broken and irreparable. Instead we used measurement of 7.6 cm away from landmark. On micro-embedded force plate, gilts were trickle fed a standard diet, up to 2.25 kg, for the 15 minutes (the proposal states .9 kg (2 lbs) but we fed up to
the full morning ration of 5 lbs just to keep them occupied during morning data collection. Days were -1 (baseline), +1 (most lame) and +6 (recovery and resolution of lameness) original proposal states a day 8 (or 7 days after induction of lameness) we only did 5 days after induction (+6).