{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:43:39Z","timestamp":1787496219133,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Distress affects animal welfare and scientific data validity. There is a lack of reports on the effects of multimodal analgesic approaches in mice. In this study, under the hypothesis that a multimodal analgesic protocol using buprenorphine with meloxicam has analgesic effects, we evaluated the effects of a multimodal analgesic protocol using buprenorphine with meloxicam on the well-being of mice during analgesic administration by changing the dosage of meloxicam. A total of 42 Slc:ICR male mice were categorized into nonsurgical and surgical groups (7 mice per group) and treated with an anesthetic (isoflurane) and analgesics (buprenorphine \u00b1 meloxicam). Analgesics were administered for 48 h after treatment. Buprenorphine (subcutaneous; 0.1 mg\/kg\/8 h) and meloxicam (subcutaneous; 0, 2.5, or 5 mg\/kg\/24 h) were administered twice. Body weight, food intake, nest consolidation score, and latency to burrow were evaluated. A significant decrease in food intake was observed 24 h after treatment, while a significant increase was observed 48 h post-treatment in all groups. Body weight showed a decreasing trend but was not significantly reduced. Furthermore, stomach, duodenum, and jejunum tissues showed no morphological abnormalities. Significant differences in burrow diving scores and the latency to burrow were observed between some groups, but these were not regarded as a consequence of the surgery and\/or the meloxicam dose. When buprenorphine and meloxicam were combined, administering up to 5 mg\/kg\/day of meloxicam for 48 h to male mice after abdominal surgery had no significant negative effects on any tested parameters. In conclusion, a multimodal analgesic protocol of buprenorphine with meloxicam is among the options for increasing well-being in mice following abdominal surgery.<\/jats:p>","DOI":"10.3390\/vetsci9110589","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T11:53:51Z","timestamp":1666785231000},"page":"589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of a Multimodal Approach Using Buprenorphine with\/without Meloxicam on Food Intake, Body Weight, Nest Consolidating Behavior, Burrowing Behavior, and Gastrointestinal Tissues in Postoperative Male Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Kayo","family":"Furumoto","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-2200","authenticated-orcid":false,"given":"Masakatsu","family":"Nohara","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagisa","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noritaka","family":"Maeta","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-3462","authenticated-orcid":false,"given":"Teppei","family":"Kanda","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Okayama University of Science, Ikoino-oka 1-3, Imabari 7948555, Ehime, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/laban.1216","article-title":"Side effects of pain and analgesia in animal experimentation","volume":"46","author":"Jirkof","year":"2017","journal-title":"Lab Anim."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Carbone, L., and Austin, J. (2016). Pain and laboratory animals: Publication practices for better data reproducibility and better animal welfare. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155001"},{"key":"ref_3","unstructured":"Institute for Laboratory Animal Research (2011). Veterinary Care. Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_4","unstructured":"Tranquilli, W.J., Thurmon, J.C., and Grimm, K.A. (2007). Veterinary Anesthesia and Analgesia, Blackwell Publishing. [4th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.4097\/kja.d.18.00217","article-title":"Designing the ideal perioperative pain management plan starts with multimodal analgesia","volume":"71","author":"Schwenk","year":"2018","journal-title":"Korean J. Anesthesiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"468","DOI":"10.30802\/AALAS-CM-19-000048","article-title":"Clinical Management of Pain in Rodents","volume":"69","author":"Foley","year":"2019","journal-title":"Comp. Med."},{"key":"ref_7","first-page":"8","article-title":"Effects of indomethacin and buprenorphine analgesia on the postoperative recovery of mice","volume":"47","author":"Blaha","year":"2008","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_8","first-page":"186","article-title":"Using cageside measures to evaluate analgesic efficacy in mice (Mus Musculus) after surgery","volume":"57","author":"Oliver","year":"2018","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_9","first-page":"466","article-title":"Effects of multimodal analgesia on the success of mouse embryo transfer surgery","volume":"50","author":"Parker","year":"2011","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1254\/jphs.11161SC","article-title":"Synergistic interaction between fentanyl and a tramadol:Paracetamol combination on the inhibition of nociception in mice","volume":"118","author":"Poveda","year":"2012","journal-title":"J. Pharmacol. Sci."},{"key":"ref_11","first-page":"71","article-title":"Lack of effect of naltrindole on the spinal synergism of morphine and non-steroidal anti-inflammatory drugs (NSAIDS)","volume":"60","author":"Miranda","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_12","first-page":"185","article-title":"Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice","volume":"50","author":"Tubbs","year":"2011","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Furumoto, K., Ogita, K., Kamisaka, T., Kawasumi, A., Takata, K., Maeta, N., Itoi, T., Nohara, M., Saeki, K., and Kanda, T. (2021). Effects of multimodal analgesic protocol, with buprenorphine and meloxicam, on mice well-being: A dose finding study. Animals, 11.","DOI":"10.3390\/ani11123420"},{"key":"ref_14","first-page":"51012","article-title":"Nest building as an indicator of health and welfare in laboratory mice","volume":"82","author":"Gaskill","year":"2013","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jneumeth.2014.02.001","article-title":"Burrowing and nest building behavior as indicators of well-being in mice","volume":"234","author":"Jirkof","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.30802\/AALAS-JAALAS-19-000027","article-title":"Effect of Repeated Exposure to Isoflurane on Nest Building and Burrowing in Mice","volume":"59","author":"Gjendal","year":"2020","journal-title":"J. Am. Assoc. Lab. Anim. Sci. JAALAS"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Arras, M., Rettich, A., Cinelli, P., Kasermann, H.P., and Burki, K. (2007). Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability. BMC Vet. Res., 3.","DOI":"10.1186\/1746-6148-3-16"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fnbeh.2010.00165","article-title":"Burrowing behavior as an indicator of post-laparotomy pain in mice","volume":"4","author":"Jirkof","year":"2010","journal-title":"Front. Behav. Neurosci."},{"key":"ref_19","first-page":"e2607","article-title":"Assessing burrowing, nest construction, and hoarding in mice","volume":"59","author":"Deacon","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.joca.2015.05.001","article-title":"Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: An objective measure of pain-related behavior and analgesic efficacy","volume":"23","author":"Bryden","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jneumeth.2015.05.019","article-title":"Assessing nest-building behavior of mice using a 3D depth camera","volume":"251","author":"Okayama","year":"2015","journal-title":"J. Neurosci. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.30802\/AALAS-CM-19-000042","article-title":"A Review of Pain Assessment Methods in Laboratory Rodents","volume":"69","author":"Turner","year":"2019","journal-title":"Comp. Med."},{"key":"ref_23","first-page":"25","article-title":"Home improvement: C57BL\/6J mice given more naturalistic nesting materials build better nests","volume":"47","author":"Hess","year":"2008","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1258\/la.2012.012027","article-title":"Individual housing of female mice: Influence on postsurgical behaviour and recovery","volume":"46","author":"Jirkof","year":"2012","journal-title":"Lab. Anim."},{"key":"ref_25","first-page":"42","article-title":"Using the mouse grimace scale to reevaluate the efficacy of postoperative analgesics in laboratory mice","volume":"51","author":"Matsumiya","year":"2012","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/0023677214562849","article-title":"Buprenorphine for pain relief in mice: Repeated injections vs sustained-release depot formulation","volume":"49","author":"Jirkof","year":"2015","journal-title":"Lab. Anim."},{"key":"ref_27","first-page":"66","article-title":"Efficacy of sustained-release buprenorphine in an experimental laparotomy model in female mice","volume":"55","author":"Kendall","year":"2016","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.pain.2006.11.003","article-title":"Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse","volume":"130","author":"Courade","year":"2007","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hohlbaum, K., Bert, B., Dietze, S., Palme, R., Fink, H., and Th\u00f6ne-Reineke, C. (2017). Severity classification of repeated isoflurane anesthesia in C57BL\/6JRj mice\u2014Assessing the degree of distress. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179588"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"802","DOI":"10.30802\/AALAS-JAALAS-19-000037","article-title":"Concentration-dependent toxicity after subcutaneous administration of meloxicam to C57BL\/6N mice (Mus musculus)","volume":"58","author":"Sarfaty","year":"2018","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_31","first-page":"610","article-title":"Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad","volume":"49","author":"Adamson","year":"2010","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nprot.2006.19","article-title":"Burrowing in rodents: A sensitive method for detecting behavioral dysfunction","volume":"1","author":"Deacon","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10918","DOI":"10.1038\/s41598-021-90331-2","article-title":"Lidocaine and buprenorphine as part of multimodal pain management in a C57BL\/6J laparotomy mouse model","volume":"11","author":"Durst","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","first-page":"617","article-title":"Comparison of buprenorphine and meloxicam for postsurgical analgesia in rats: Effects on body weight, locomotor activity, and hemodynamic parameters","volume":"49","author":"Bourque","year":"2010","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.physbeh.2010.01.038","article-title":"Housing environment influences the need for pain relief during post-operative recovery in mice","volume":"99","author":"Pham","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1258\/002367707782314328","article-title":"Impact of \u201cliving apart together\u201d on postoperative recovery of mice compared with social and individual housing","volume":"41","author":"Kuin","year":"2007","journal-title":"Lab. Anim."},{"key":"ref_37","first-page":"106","article-title":"Pre-warming following premedication limits hypothermia before and during anesthesia in Sprague-Dawley rats (Rattus Norvegicus)","volume":"85","author":"Rufiange","year":"2021","journal-title":"Can. J. Vet. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"195","DOI":"10.30802\/AALAS-JAALAS-20-000089","article-title":"Effects of Cling Film Draping Material on Body Temperature of Mice during Surgery","volume":"60","author":"Celeste","year":"2021","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_39","first-page":"e62593","article-title":"Handling techniques to reduce stress in mice","volume":"2021","author":"Marcotte","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1292\/jvms.18-0044","article-title":"Tunnel use facilitates handling of ICR mice and decreases experimental variation","volume":"80","author":"Nakamura","year":"2018","journal-title":"J. Vet. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nmeth.1500","article-title":"Taming anxiety in laboratory mice","volume":"7","author":"Hurst","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14562","DOI":"10.1038\/s41598-020-71476-y","article-title":"Benefits of tunnel handling persist after repeated restraint, injection and anaesthesia","volume":"10","author":"Henderson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gouveia, K., and Hurst, J.L. (2013). Reducing Mouse Anxiety during Handling: Effect of Experience with Handling Tunnels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066401"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.pbb.2020.172877","article-title":"Analgesic treatment with buprenorphine should be adapted to the mouse strain","volume":"191","author":"Rudeck","year":"2020","journal-title":"Pharmacol. Biochem. Behav."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/9\/11\/589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:58Z","timestamp":1760144578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/9\/11\/589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,26]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["vetsci9110589"],"URL":"https:\/\/doi.org\/10.3390\/vetsci9110589","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,26]]}}}