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Analgesic efficacy of sodium salicylate in an amphotericin B-induced bovine synovitis-arthritis model

J. L. Kotschwar^*, J. F. Coetzee^*,1, D. E. Anderson^*, R. Gehring^*, B. KuKanich and M. D. Apley^*

^* Department of Clinical Sciences, and
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan 66506-5601

¹ Corresponding author: jcoetzee{at}vet.ksu.edu

This study examined the efficacy of sodium salicylate for providing analgesia in an amphotericin B-induced bovine synovitis-arthritis model using 10 male Holstein calves, 4 to 6 mo old and weighing approximately 250 kg. The study used a repeated measures partial crossover design with 2 phases, consisting of 3 treatment periods within each phase. Calves were blocked by body weight and randomly assigned to the sodium salicylate (50 mg/kg i.v.) or placebo group for phase 1. In period 1, lameness induction was simulated with a needle prick of the coronary band, followed by drug or placebo administration. At predetermined time points, serial blood samples for cortisol and salicylate concentrations, electrodermal activity measurements, heart rates, and pressure mat data were collected. Visual lameness scores were recorded by an observer blinded to treatments. In period 2, lameness was induced with injection of amphotericin B into the distal interphalangeal joint, followed by drug or placebo administration, with sample collection as described previously. In period 3, the drug or placebo was administered to the respective calves with sample collection. After a 10-d washout period, phase 2 was conducted with treatments crossed over between groups. Cortisol and salicylate samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay, respectively. The pharmacokinetic data were analyzed using compartmental analysis. Mean intravenous salicylate apparent volume of distribution was 0.2 ± 0.005 L/kg, total body clearance was 4.3 ± 0.2 mL/min·kg, and elimination half-life was 36.9 ± 1.2 min. The repeated measures data were analyzed based on a univariate split-plot approach with a random effects-mixed model. Differences in stance phase duration and serum cortisol concentration values were seen both between periods and between treatment group x periods; differences in heart rate, contact surface area, and contact pressure values were seen between periods, suggesting that our lameness model was effective. No differences were seen between treatment groups. When analyzed by visual lameness score, differences were seen in heart rate, contact surface area, contact pressure, and cortisol concentrations. Area under the time-effect curves, determined by using the trapezoidal rule, had results similar to the repeated measures data, except for a difference in period for electrodermal activity. This amphotericin B-induced synovitis-arthritis model is a useful tool for studying changes associated with lameness in cattle. Sodium salicylate was not effective in providing analgesia after lameness.

Key Words: salicylate • amphotericin B • lameness • pain