{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:11:28Z","timestamp":1788775888778,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Wool Education Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Routine husbandry procedures in sheep induce significant and prolonged pain and inflammation, which often exceeds the duration of action of current commercially available analgesics. Mavacoxib is a selective cyclooxygenase-2 (COX-2) inhibitor approved for canine osteoarthritis treatment. With a half-life exceeding two weeks in dogs, mavacoxib may represent a candidate for investigating whether extended-duration analgesia can be achieved in sheep and more closely aligned with the duration of post-procedural inflammation and pain. This article examines the physiological and behavioural indicators of sheep pain, the limitations of current analgesic strategies, and the pharmacological rationale for mavacoxib as a candidate for pain management in sheep. Further research into its pharmacokinetics, efficacy, and safety in sheep is essential to improve welfare and overcome practical barriers to analgesia in extensive grazing systems.<\/jats:p>","DOI":"10.3390\/ani16172791","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Potential of Selective COX-2 Inhibitor Mavacoxib for Extended Analgesia in Sheep Husbandry"],"prefix":"10.3390","volume":"16","author":[{"given":"Oliver","family":"Fioretto","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7831-4724","authenticated-orcid":false,"given":"Lee","family":"Metcalf","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-5788","authenticated-orcid":false,"given":"Sabrina","family":"Lomax","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1751-0813.2009.00429.x","article-title":"Effects of a topical anaesthetic formulation and systemic carprofen, given singly or in combination, on the cortisol and behavioural responses of Merino lambs to castration","volume":"87","author":"Paull","year":"2009","journal-title":"Aust. Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Steagall, P.V., Bustamante, H., Johnson, C.B., and Turner, P.V. (2021). Pain Management in Farm Animals: Focus on Cattle, Sheep and Pigs. Animals, 11.","DOI":"10.3390\/ani11061483"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/avj.12031","article-title":"Duration of action of a topical anaesthetic formulation for pain management of mulesing in sheep","volume":"91","author":"Lomax","year":"2013","journal-title":"Aust. Vet. J."},{"key":"ref_4","unstructured":"(2025, April 08). Sheep Sustainability Framework. On-Farm Insights from the National Producer Survey, October 2022. Available online: https:\/\/www.sheepsustainabilityframework.com.au\/globalassets\/sheep-sustainability\/media\/sheep-sustainabilty-framework-2022-on-farm-insights-report_updated-nov-23_web.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cohen, S., Foss, E., Beths, T., and Musk, G.C. (2024). An Exploration of Analgesia Options for Australian Sheep. Animals, 14.","DOI":"10.3390\/ani14070990"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Small, A., Fisher, A.D., Lee, C., and Colditz, I. (2021). Analgesia for Sheep in Commercial Production: Where to Next?. Animals, 11.","DOI":"10.3390\/ani11041127"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nateghi Baygi, M., Metcalf, L.N., Kimble, B., and Lomax, S. (2026). When Pain Outlasts Our Drugs: The Case for Sustained-Release Analgesia in Sheep. Animals, 16.","DOI":"10.3390\/ani16030505"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Metcalf, L., Lomax, S., Van der Saag, D., Garg, S., and White, P.J. (2024). Pain Relief Interventions in Australian Livestock Husbandry: A Review of Animal Welfare and Pain Duration. Animals, 14.","DOI":"10.3390\/ani14131901"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-1-1","article-title":"The Journal of Inflammation","volume":"1","author":"Punchard","year":"2004","journal-title":"J. Inflamm."},{"key":"ref_10","unstructured":"Hannoodee, S., and Nasuruddin, D.N. (2022). Acute Inflammatory Response, StatPearls Publishing."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Di Maio, G., Villano, I., Ilardi, C.R., Messina, A., Monda, V., Iodice, A.C., Porro, C., Panaro, M.A., Chieffi, S., and Messina, G. (2023). Mechanisms of Transmission and Processing of Pain: A Narrative Review. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20043064"},{"key":"ref_12","first-page":"2","article-title":"Assessment of pain: Types, mechanism and treatment","volume":"1","author":"Swieboda","year":"2013","journal-title":"Ann. Agric. Environ. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S144","DOI":"10.1097\/00002508-200009001-00006","article-title":"Pain mechanisms and management: A central perspective","volume":"16","author":"Mannion","year":"2000","journal-title":"Clin. J. Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12974-020-1703-1","article-title":"Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception","volume":"17","author":"Jang","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2527\/1997.751266x","article-title":"Assessment of acute pain in farm animals using behavioral and physiological measurements","volume":"75","author":"Molony","year":"1997","journal-title":"J. Anim. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and Inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1021\/jm0613166","article-title":"Structural and Functional Basis of Cyclooxygenase Inhibition","volume":"50","author":"Blobaum","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_18","first-page":"9","article-title":"Analgesic, anti-inflammatory, antipyretic drugs","volume":"1","author":"Lees","year":"2009","journal-title":"Vet. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jvp.12185","article-title":"Pharmacokinetics, pharmacodynamics, toxicology and therapeutics of mavacoxib in the dog: A review","volume":"38","author":"Lees","year":"2015","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Flood, J., and Stewart, A.J. (2022). Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses. Animals, 12.","DOI":"10.3390\/ani12212939"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.tcm.2015.03.006","article-title":"Elevation of cardiovascular risk by non-steroidal anti-inflammatory drugs","volume":"25","author":"Anwar","year":"2015","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.applanim.2011.09.008","article-title":"The effects of age and sex on pain sensitivity in young lambs","volume":"135","author":"Guesgen","year":"2011","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e15092","DOI":"10.7717\/peerj.15092","article-title":"Sex impacts pain behaviour but not emotional reactivity of lambs following ring tail docking","volume":"11","author":"Marini","year":"2023","journal-title":"PeerJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.applanim.2014.07.008","article-title":"Social context and other factors influence the behavioural expression of pain by lambs","volume":"159","author":"Guesgen","year":"2014","journal-title":"Appl. Anim. Behav. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"M13.1","DOI":"10.1590\/0103-8478cr20180336","article-title":"Systemic inflammatory and stress markers in cattle and sheep submitted to different reproductive procedures","volume":"48","author":"Costa","year":"2018","journal-title":"Ci\u00eanc. Rural"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1751-0813.2011.00809.x","article-title":"Development of a lameness model in sheep for assessing efficacy of analgesics","volume":"89","author":"Colditz","year":"2011","journal-title":"Aust. Vet. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/avj.12779","article-title":"Efficacy of meloxicam in a pain model in sheep","volume":"97","author":"Colditz","year":"2019","journal-title":"Aust. Vet. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Woodland, A.N., Van der Saag, D., Kimble, B., White, P.J., Govendir, M., and Lomax, S. (2019). Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215842"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/avj.12351","article-title":"Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep","volume":"93","author":"Marini","year":"2015","journal-title":"Aust. Vet. J."},{"key":"ref_30","unstructured":"Beekhuis, L. (2025, October 11). Pain Recognition and Management in Cattle: An Overview. Available online: https:\/\/www.veterinary-practice.com\/article\/pain-recognition-and-management-in-cattle."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Johnston, C.H., Whittaker, A.L., Franklin, S.H., and Hutchinson, M.R. (2022). The Neuroimmune Interface and Chronic Pain Through the Lens of Production Animals. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.887042"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.njas.2013.05.003","article-title":"Assessing and controlling health risks from animal husbandry","volume":"66","author":"Kimman","year":"2013","journal-title":"NJAS-Wagening. J. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.3168\/jds.2009-2604","article-title":"Relationship between cortisol response to stress and behavior, immune profile, and production performance of dairy ewes","volume":"93","author":"Caroprese","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"de la Puente, R., Diez, R., Diez, M.J., Fernandez, N., Sahagun, A.M., Rodriguez, J.M., Garcia, J.J., and Lopez, C. (2024). Pharmacokinetics of Meloxicam in Different Animal Species: A Comprehensive Review. Vet. Sci., 11.","DOI":"10.3390\/vetsci11110519"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.1111\/jsap.12200","article-title":"Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council members and co-authors of this document","volume":"55","author":"Mathews","year":"2014","journal-title":"J. Small Anim. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cvfa.2012.11.008","article-title":"A Review of Analgesic Compounds Used in Food Animals in the United States","volume":"29","author":"Coetzee","year":"2013","journal-title":"Vet. Clin. North Am. Food Anim. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2527\/af.2012-0049","article-title":"Achieving pain control for routine management procedures in North American beef cattle","volume":"2","author":"Fierheller","year":"2012","journal-title":"Anim. Front."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1365-2885.2010.01165.x","article-title":"The pharmacokinetics of mavacoxib, a long-acting COX-2 inhibitor, in young adult laboratory dogs","volume":"33","author":"Cox","year":"2010","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wilson, S.E., Carpenter, J.W., Gardhouse, S., and KuKanich, B. (2023). Pharmacokinetics of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus). Am. J. Vet. Res., 84.","DOI":"10.2460\/ajvr.22.11.0196"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12043","DOI":"10.1038\/s41598-017-12159-z","article-title":"Comparative population pharmacokinetics and absolute oral bioavailability of COX-2 selective inhibitors celecoxib, mavacoxib and meloxicam in cockatiels (Nymphicus hollandicus)","volume":"7","author":"Dhondt","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","unstructured":"Antonissen, G., Martel, A., and Goessens, T. (2015, January 18\u201323). Comparative pharmacokinetics of celecoxib and mavacoxib in cockatiels (Nymphicus hollandicus). Proceedings of the 2nd International Conference, Paris, France."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1638\/2019-0161","article-title":"Pharmacokinetics of oral mavacoxib in Caribbean Flamingos (Phoenicopterus ruber ruber)","volume":"51","author":"Huckins","year":"2020","journal-title":"J. Zoo Wildl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2460\/ajvr.80.2.201","article-title":"Pharmacokinetics of meloxicam during multiple oral or intramuscular dose administration to African grey parrots (Psittacus erithacus)","volume":"80","author":"Montesinos","year":"2019","journal-title":"Am. J. Vet. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.18773\/austprescr.2000.034","article-title":"COX-2 inhibitors","volume":"23","author":"Brooks","year":"2000","journal-title":"Aust. Prescr."},{"key":"ref_45","unstructured":"Edwards, S.H. (2025, May 03). Nonsteroidal Anti-inflammatory Drugs in Animals. Available online: https:\/\/www.msdvetmanual.com\/pharmacology\/inflammation\/nonsteroidal-anti-inflammatory-drugs-in-animals."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"802","DOI":"10.2460\/ajvr.2000.61.802","article-title":"In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase activity in dogs","volume":"61","author":"Benn","year":"2000","journal-title":"Am. J. Vet. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1939-1676.2005.tb02741.x","article-title":"The Coxib NSAIDs: Potential Clinical and Pharmacologic Importance in Veterinary Medicine","volume":"19","author":"Bergh","year":"2005","journal-title":"J. Vet. Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1056\/NEJMp048288","article-title":"Coxibs and Cardiovascular Disease","volume":"351","author":"FitzGerald","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_49","unstructured":"Plumlee, K.H. (2004). Clinical Veterinary Toxicology, Mosby. [1st ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cvsm.2018.06.003","article-title":"Toxicology of Frequently Encountered Nonsteroidal Anti-inflammatory Drugs in Dogs and Cats: An Update","volume":"48","author":"McLean","year":"2018","journal-title":"Vet. Clin. North Am. Small Anim. Pract."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fritz, S.A., Ensley, S.M., Lawrence, J.R., Van Engen, N., Lin, Z., Kleinhenz, M.D., Wulf, L.W., Rice, S., Gorden, P.J., and Peterson, J. (2023). Pharmacokinetics, Milk Residues, and Toxicological Evaluation of a Single High Dose of Meloxicam Administered at 30 mg\/kg per os to Lactating Dairy Cattle. Vet. Sci., 10.","DOI":"10.3390\/vetsci10040301"},{"key":"ref_52","unstructured":"Zoetis UK Ltd. (2025, October 09). Trocoxil 20 mg Chewable Tablets for Dogs SUMMARY OF PRODUCT CHARACTERISTICS, Available online: https:\/\/www.vmd.defra.gov.uk\/productinformationdatabase\/files\/SPC_Documents\/SPC_2648143.PDF."},{"key":"ref_53","unstructured":"Wittek, T. (2025, October 09). Abomasal Ulcers in Cattle. Available online: https:\/\/www.msdvetmanual.com\/digestive-system\/diseases-of-the-abomasum\/abomasal-ulcers-in-cattle."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2885.2004.00605.x","article-title":"Plasma clearance","volume":"27","author":"Toutain","year":"2004","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/rheumatology\/35.suppl_1.13","article-title":"A review of the clinical pharmacokinetics of meloxicam","volume":"35","author":"Roth","year":"1996","journal-title":"Br. J. Rheumatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e70122","DOI":"10.1111\/cbdd.70122","article-title":"Synthesis Methods and Therapeutic Journey of Carprofen and Its Derivatives: A Review","volume":"105","author":"Limban","year":"2025","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1136\/vr.102397","article-title":"Comparative efficacy and safety of mavacoxib and carprofen in the treatment of canine osteoarthritis","volume":"176","author":"Becskei","year":"2015","journal-title":"Vet. Rec."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pang, L.Y., Argyle, S.A., Kamida, A., Morrison, K.O.N., and Argyle, D.J. (2014). The long-acting COX-2 inhibitor mavacoxib (Trocoxil\u2122) has anti-proliferative and pro-apoptotic effects on canine cancer cell lines and cancer stem cells in vitro. BMC Vet. Res., 10.","DOI":"10.1186\/s12917-014-0184-9"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1002\/jps.10174","article-title":"Interspecies scaling of biliary excreted drugs","volume":"91","author":"Mahmood","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1365-2885.2004.00617.x","article-title":"Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest","volume":"27","author":"Lees","year":"2004","journal-title":"J. Vet. Pharmacol. Ther."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/17\/2791\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:45:49Z","timestamp":1788774349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/17\/2791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":60,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ani16172791"],"URL":"https:\/\/doi.org\/10.3390\/ani16172791","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}