Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.
Abstract: To compare the analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAID), ketoprofen (2.20 and 3.63 mg/kg of body weight) and phenylbutazone (4.40 mg/kg), in an acute equine synovitis model. Methods: 4 groups of 6 horses received NSAID or saline solution in a randomized design. Methods: 24 clinically normal mares and geldings. Methods: Left intercarpal joints were injected with sterile carrageenan to induce synovitis at the same time as IV administration of NSAID or saline solution. Clinical assessments were made and synovial fluid was withdrawn at 0, 1, 3, 6, 9, 12, 24, and 48 hours. Results: The eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4, increased in synovial fluid after synovitis induction in all horses then returned to near baseline by 48 hours. All NSAID-treated horses had decreased PGE2, compared with saline-treated horses. This effect lasted longer in phenylbutazone-treated horses than in ketoprofen-treated horses. There were no treatment effects on leukotriene B4. In saline-treated animals, lameness, joint temperature, and synovial fluid volume, protein concentration, and nucleated cells increased 3 to 12 hours after induction, with marked reduction by 48 hours. Only phenylbutazone treatment reduced lameness, joint temperature, and synovial fluid volume. Conclusions: Phenylbutazone was more effective than ketoprofen in reducing lameness, joint temperature, synovial fluid volume, and synovial fluid PGE2. Results do not support lipoxygenase inhibition by either NSAID. Conclusions: This reversible model induced synovial fluid alterations similar to those observed in horses with septic arthritis. Results indicate that phenylbutazone may be more useful than ketoprofen in treating acute joint inflammation.
Publication Date: 1996-06-01 PubMed ID: 8725815
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- Clinical Trial
- Comparative Study
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates how two nonsteroidal anti-inflammatory drugs – Ketoprofen and Phenylbutazone – impact inflammation in horse joints. The study found that Phenylbutazone was more effective in reducing symptoms of inflammation.
Research Methodology
- The experiment involved four groups of six horses, which received either the nonsteroidal anti-inflammatory drugs (NSAID) ketoprofen and phenylbutazone, or a saline solution in a randomized configuration.
- The horses involved in the study were clinically normal mares and geldings.
- To create inflammation experimentally, the researchers injected the horse’s left intercarpal joints with sterile carrageenan at the same instance as the administration of NSAID or saline solution.
- Numerous parameters were observed and measurements were taken at specific intervals: at 0, 1, 3, 6, 9, 12, 24, and 48 hours. These parameters included clinical assessments and synovial fluid withdrawal.
Research Findings
- Following the induction of inflammation, increases were noted in the synovial fluid of the eicosanoids: Prostaglandin E2 (PGE2) and leukotriene B4. However, by the 48 hours mark, levels were found to have almost returned to their initial, baseline levels.
- All horses treated with NSAID had decreased PGE2 compared to those treated with saline solution. Phenylbutazone-treated horses maintained this effect for a longer duration than those treated with Ketoprofen.
- The treatment showed no effect on levels of leukotriene B4.
- In the horses treated with saline, an increase in lameness, joint temperature, and synovial fluid characteristics such as volume, protein concentration, and nucleated cells were observed from 3 to 12 hours post-induction. These indicators were markedly reduced by the 48-hour mark.
- Only Phenylbutazone was found to diminish lameness, joint temperature and synovial fluid volume.
Conclusions
- The study revealed that Phenylbutazone was more effective than Ketoprofen in reducing the primary symptoms of inflammation – such as lameness, elevated joint temperature, and synovial fluid alterations.
- The results did not show any evidence to suggest that either NSAID inhibits lipoxygenase.
- The researchers concluded that the experimental model used to induce inflammation in the horse’s joint effectively mimics the synovial fluid alterations observed in horses with septic arthritis. They also suggest that Phenylbutazone could be more beneficial than Ketoprofen in managing acute joint inflammation in horses.
Cite This Article
APA
Owens JG, Kamerling SG, Stanton SR, Keowen ML, Prescott-Mathews JS.
(1996).
Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.
Am J Vet Res, 57(6), 866-874.
Publication
Researcher Affiliations
- Department of Veterinary Physiology, Pharmacology, and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
MeSH Terms
- Acute Disease
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
- Dinoprostone / analysis
- Dinoprostone / metabolism
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Horse Diseases / chemically induced
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horses
- Joints / metabolism
- Joints / physiopathology
- Ketoprofen / therapeutic use
- Lameness, Animal / etiology
- Lameness, Animal / physiopathology
- Leukotriene B4 / analysis
- Leukotriene B4 / metabolism
- Male
- Phenylbutazone / therapeutic use
- Proteins / analysis
- Synovial Fluid / chemistry
- Synovitis / chemically induced
- Synovitis / drug therapy
- Synovitis / veterinary
Citations
This article has been cited 17 times.- Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses. Animals (Basel) 2022 Oct 26;12(21).
- Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Front Vet Sci 2022;9:907616.
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- Chakrabarti S, Ai M, Henson FMD, Smith ESJ. Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies. Neurobiol Pain 2020 Aug-Dec;8:100051.
- Donnell JR, Frisbie DD. Use of firocoxib for the treatment of equine osteoarthritis. Vet Med (Auckl) 2014;5:159-168.
- Sotelo EDP, Vendruscolo CP, Fülber J, Seidel SRT, Jaramillo FM, Agreste FR, Silva LCLCD, Baccarin RYA. Effects of Joint Lavage with Dimethylsulfoxide on LPS-Induced Synovitis in Horses-Clinical and Laboratorial Aspects. Vet Sci 2020 Apr 30;7(2).
- Stack JD, Cousty M, Steele E, Handel I, Lechartier A, Vinardell T, David F. Comparison of Serum Amyloid A Measurements in Equine Synovial Fluid With Routine Diagnostic Methods to Detect Synovial Infection in a Clinical Environment. Front Vet Sci 2019;6:325.
- Niemelä TM, Tulamo RM, Aaltonen K, Sankari SM, Hielm-Björkman AK. Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: a randomised double-blind clinical trial. BMC Vet Res 2018 Jun 15;14(1):186.
- Guedes AGP, Aristizabal F, Sole A, Adedeji A, Brosnan R, Knych H, Yang J, Hwang SH, Morisseau C, Hammock BD. Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis. J Vet Pharmacol Ther 2018 Apr;41(2):230-238.
- Baccarin RY, Rasera L, Machado TS, Michelacci YM. Relevance of synovial fluid chondroitin sulphate as a biomarker to monitor polo pony joints. Can J Vet Res 2014 Jan;78(1):50-60.
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- Freitas GC, Carregaro AB, Gehrcke MI, De La Côrte FD, Lara VM, Pozzobon R, Brass KE. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis. Can J Vet Res 2011 Apr;75(2):141-6.
- de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009;11(2):R35.
- Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel) 2025 Aug 22;15(17).
- Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment. Animals (Basel) 2023 Oct 12;13(20).
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