Source: UNIVERSITY OF ARKANSAS submitted to
MANAGING PAIN IN CATTLE UNDERGOING CASTRATION USING A BIODEGRADABLE MICRONEEDLE PATCH CONTAINING MELOXICAM
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1024984
Grant No.
2021-67015-34082
Cumulative Award Amt.
$500,000.00
Proposal No.
2020-05247
Multistate No.
(N/A)
Project Start Date
Jun 1, 2021
Project End Date
Jun 30, 2021
Grant Year
2021
Program Code
[A1251]- Animal Health and Production and Animal Products: Animal Well-Being
Recipient Organization
UNIVERSITY OF ARKANSAS
(N/A)
FAYETTEVILLE,AR 72703
Performing Department
Animal Science
Non Technical Summary
Delivery of pain medicaton to animals is most often administeredvia injections or orally through suspension or tablet form. These methods of drug administration often require repeated dosing which is not ideal forlivestock practices. Since pain medication must be administered frequently (often every 12 to 24 hours), handling and restraining the animal can cause significant stress to the post-surgical animal. This project will studya better approach for drug deliverytocattle through using atransdermal application witha biodegradable chitosanmicroneedle patch. We hypothesize thistechnology will deliver a convenient method to minimize or eliminate some of the negative impacts of post-surgical pain on cattle wellbeing, health and gain performance. This project willevaluate the efficacy of an engineered chitosan microneedle patch containing meloxicam, a non-steroidal anti-inflammatory drug,for managing post-surgicalpainin male beef calves.Our project will focus on evaluatingthis novel methodology for the delivery of meloxicam for long term pain managementin cattlefollowinga surgical castration and its effect on the physiologic and inflammatory responses. We also seek to evaluate the long term effect of the microneedle patch on calf growth, behaviorand meat quality. Ultimately, we hope thepatch will provide a novel pain management strategy that could be easily implemented by the cattle industry. In addition, our work will be applicable to veterinary professionals that haveinterest in providing an effective long term methodof controlling post-surgicalpain in their practice.
Animal Health Component
75%
Research Effort Categories
Basic
25%
Applied
75%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
31533101020100%
Goals / Objectives
Our objective is to evaluate the efficacy of a meloxicam-microneedle patch for post-surgical physiologic and inflammatory responsefollowing castration inmale calves.We also plan to evaluate the long-term effects of meloxicam-chitosam microneedle patch on growth performance and carcass quality in castrated male beef calves.
Project Methods
1. This study will evaluate the effect of a meloxicam-chitosan needle patch on post-surgical physiologic and inflammatory responses of castrated bull calves. Twenty-four male crossbred Angus calves will be obtained. Calves will consist of intact bulls (n = 24) with average body weight (BW) = ± 175 kg. Calves will be managed as two blocks with twelve animals per block arriving at two time points, and they will arrive and be given a 2-wk acclimation period before study commencement.After acclimation, animals will be housed in individual stanchions for the first 3 days of the study for serial blood collections to occur then placed back into their assigned pen for the duration of the study. A 24-hour acclimation period will be allotted before castration to mitigate stress experienced from acclimation to the stanchions and the jugular catheterization procedure. Calves will be fed a calf starter diet at 2.5% of BW per day. The diet will consist of rolled corn, dried distiller's grains, soybean meal, cottonseed hulls, and a vitamin and trace mineral supplement. Water will be offered ad libitum in automatic water troughs. Twenty-four calves will be assigned to 1 of 2 treatments (n = 12 calves/treatment) with the twelve bull calves randomly assigned to receive either a placebo (CON) or meloxicam-chitosan needle patch (MEL) prior to castration. On day one, cattle will be restrained in a squeeze chute for administration of the meloxicam-chitosan needle patches, and at the same time, an indwelling catheter will be placed into the jugular vein of all study animals to facilitate intensive, serial blood collection.A 14-gauge catheter will be inserted and sutured in place and remain in order to make repeated blood samples for the first 72 hours of the study. On day zero, castration will be performed surgically by removal of the ventral one-third of the scrotum, then testes pulled from the inside of the scrotum, and the spermatic cord will be severed with a #22 blade scalpel. Blood samples will be repeatedly collected from all calves to measure substance P (SP), complete blood count (CBC), cortisol, prostaglandin E2 (PE), haptoglobin (Hp) and meloxicam plasma concentrations. Substance P, cortisol, and meloxicam plasma concentrations will be measured at the time of patch application (day1), time of castration (0 hr), 1 hr, 3 hr, 6 hr, 12 hr, day 1, day 2, day 3, day 7, and day 10. Prostaglandin E2 and haptoglobin will be measured on day 0, day 1, day 2, day 3 and day 7. Cortisol and haptoglobin samples will be collected into a serum clot 6 mL activator tubes, blood for SP and CBC analysis will be collected into an EDTA tube, and drug concentration and PE blood samples will be collected into lithium heparin tubes. The EDTA tubes and lithium heparin tubes will be stored on ice and the serum tubes will be stored at room temperature before centrifugation. Within 4 h of collection, blood will be centrifuged at 2,100 × g for 20 min at 20°C, and serum will be decanted into duplicate aliquots and stored at -20°C for subsequent analyses. Whole blood samples will be analyzed within 4 hours of collection to determine total and differential (lymphocytes, neutrophils, monocytes, eosinophils, and basophils) white blood cell count (WBC), platelets, red blood cell count (RBC), hemoglobin, and hematocrit using an automated hemocytomter. Neutrophil to lymphocyte ratio (N:L) will calculated by dividing the total number of neutrophils by the total number of lymphocytes for each collection point. Aliquots d-1, d0, 1 hr, 3 hr, 6 hr, 12 hr, d1, d2, d3, d7, and d10 for determination of SP and meloxicam plasma concentrations. A second aliquot will be used to determine serum Hp, PE and cortisol concentrations using a bovine-specific Hp ELISA kit, or a PE ELISA kit and a radioimmunoassay for cortisol analysis.2. This study will evaluate the effect of a meloxicam-chitosan needle patch on post-surgical growth performance and carcass quality in castrated male beef calves. Thirty-six male crossbred Angus calves will be obtained. Calves will consist of bulls (n = 24) and steers (n = 12) with average body weight (BW) = ± 175 kg. Calves will be managed in two blocks with eighteen animals per block that will arrive to the research facility at two separate time points. Stalls will be randomly assigned to calves upon arrival, and calves be given a 2-week acclimation period before study commencement. After day 28 of the study, calves will be commingled and moved to a series of twelve 2.4 ha pens and grazed as a single group being rotated through the pastures to supply adequate forage needs. The pens will contain mixed-grass forage and calves will be maintained there for an additional 152-day period to complete the grazing phase of the study. During grazing, the feed management approach will designed to provide cattle with ad libitum hay if forage is limiting and a supplemental commodity ration intended to achieve approximately 0.68 kg of gain/d which will be fed daily. Around day 200, calves will be shipped to a feedlot and fed a total mixed ration until reaching harvest weight. Calves will be assigned to a single feedlot pen and fed a common feedlot ration throughout the finishing period. When steers are determined by feedlot personnel to reach a suitable degree of finish, they will be transported to a commercial processing plant for harvest. Study cattle will consist of twelve bulls (n = 24) and six steers (n = 12) with average body weight (BW) = ± 100 kg with bull calves being randomly assigned to one of two treatments and the twelve steers serving as a negative control group. Twelve bulls will be randomly assigned to two treatments with twelve receiving a placebo chitosan patch (BULL) and twelve receiving a meloxicam-chitosan needle patch (MEL) 1 day prior to surgical castration. The twelve steer calves will serve as negative control (CON). Castration will be performed surgically. Calf behavioral activity will be monitored for the 28-day post-castration period on all calves using a 3-axis accelerometer attached to the right metatarsus using a plastic strap. Accelerometers will be attached to each calf from day 7 through day 28 to observe behavior. The accelerometers will log data including: time spent standing, time spent lying, number of steps taken, number of lying bouts, and a motion index determined from a proprietary algorithm. A baseline value for each behavior variable will be determined for each treatment by determining the behavior variable means recorded from days −7 to −1. During processing and castration on days -7, 0, 7, 14 and 28, animal temperament will be evaluated on each animal while restrained in the hydraulic squeeze chute using a 4-point scale. Individual body weights (BW) will be recorded throughout the study on days -7, 0, 7, 14, 28, 56, 84, 112, 140, 168 182 (feedlot entry), interim feedlot weight, and harvest weight. Calves will be assigned to a single feedlot pen and fed a common feedlot ration throughout the finishing period. When steers are determined by feedlot personnel to reach a suitable degree of finish, they will be transported to a commercial processing plant for harvest. Backfat thickness (BF), rib eye area (REA), HCW, marbling score, quality grade (QG), and yield grade (YG) data will recorded at harvest of the study calves by a trained technician.

Progress 06/01/21 to 03/23/21

Outputs
Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Final report was submitted to rectify technical issue in order to transfergrant award.

Publications