Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

Digranes, N., Haga, H. A., Nordgreen, J. 2023. High and hyper: Fentanyl induces psychomotor side-effects in healthy pigs. Animals 13(10), 1671.

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin...

Eeza, M. N. H., Singer, R., Ding, Y. et al. 2023. Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging. PLOS ONE 18(4), e0284215.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead to...

Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Malik, A., Zavadil, J. A., Geusz, M. E. 2023. Using bioluminescence to image gene expression and spontaneous behavior in freely moving mice. PLOS ONE 18(1), e0279875.

Bioluminescence imaging (BLI) of gene expression in live animals is a powerful method for monitoring development, tumor growth, infections, healing, and other progressive, long-term biological processes. BLI remains an effective approach for reducing the number...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Miller, R., Grott, A., Patzkéwitsch, D. et al. 2023. Behavior of piglets in an observation arena before and after castration with local anesthesia. Animals 13(3), 529.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

Palumbo, G., Kunze, L. H., Oos, R. et al. 2023. Longitudinal studies on Alzheimer disease mouse models with multiple tracer PET/CT: Application of reduction and refinement principles in daily practice to safeguard animal welfare during progressive aging. Animals 13(11), 1812.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt...

Ruvira, S., Rodríguez-Rodríguez, P., Cañas, S. et al. 2023. Evaluation of parameters which influence voluntary ingestion of supplements in rats. Animals 13(11), 1827.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based...

Wolter, A., Bucher, C. H., Kurmies, S. et al. 2023. A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models. Scientific Reports 13(1), 3824.

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are...

Costa, G. L., Spadola, F., Di Pietro, S. et al. 2023. Tramadol vs. Lidocaine administered intraperitoneally and in incisional lines for the intraoperative and postoperative pain management of romifidine-telazol-anesthetized swine undergoing umbilical hernia repair. Animals 13(18), 2905.

The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred swine. The...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

Trujanovic, R., Rohrbach, H. 2023. Ultrasound-guided block of the sciatic and the femoral nerves in rabbits—A descriptive anatomical study. Animals 13(14), 2393.

The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their...

Krall, C., Hopper, L. M., Hutchinson, E. K. 2023. Mice just want to have fun: Playpens facilitate faster training in non-invasive techniques for improved refinement and well-being. Laboratory Animal Science Professional 11(4) (July/August), 22-24.

Practical mechanisms that can be implemented by animal facilities to enhance refinement include the use of non-aversive handling, non-invasive alternative procedures, and additional environmental enrichment. Thus, we sought to collate these techniques by developing a...

Benato, L., Murrell, J., Rooney, N. 2023. Determining a cut-off point for intervention analgesia in rabbits using the Bristol Rabbit Pain Scale. Veterinary Record 193(5), e2995.

Background: The objective of this study was to determine the threshold of the Bristol Rabbit Pain Scale (BRPS) indicating the need for intervention analgesia. Methods: Fourteen members of veterinary staff were recruited to rate rabbits...

Brake, M. E., Russ, B. P., Gansebom, S. et al. 2023. Effects of extended-release buprenorphine on mouse models of influenza. Comparative Medicine 73(6), 466–473.

Mice are widely used as small animal models for influenza infection and immunization studies because of their susceptibility to many strains of influenza, obvious clinical signs of infection, and ease of handling. Analgesia is rarely...

Buhr, P., Kolstrup, S., Nikolajsen, L.-L. et al. 2023. The anaesthetic effects of ketamine/xylazine/midazolam in C57Bl/6JRj mice. Scandinavian Journal of Laboratory Animal Science 49, 21–27.

We wished to improve the efficacy and safety of ketamine/xylazine anaesthesia in C57Bl/6JRj mice and achieve a surgical anaesthesia lasting 20-30 minutes, aiming at fewer anaesthesia related deaths and using the subcutaneous injection route to...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

Lopez-Echeverria, G., Alamaw, E., Gorman, G. et al. 2023. Comparing three formulations of buprenorphine in an incisional pain model in mice. JAALAS 62(6), 531–537.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based...

McKenna, B. A., Weaver, H. L., Kim, J. et al. 2023. A pharmacokinetic and analgesic efficacy study of carprofen in female CD1 mice. JAALAS 62(6), 545–552.

The minimization of pain in research animals is a scientific and ethical necessity. Carprofen is commonly used for pain management in mice; however, some data suggest that the standard dosage of 5 mg/kg may not...

Miguelena Chamorro, B., Swaminathan, G., Mundt, E. et al. 2023. Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance. Lab Animal 52(9), 195–197.

Oral vaccines are gaining attention for their ease of administration and ability to activate mucosal immune responses. However, preclinical studies using this route often require the use of gavage, which has limitations. In this comment...

Illario, J. A., Osborn, K. G., Garcia, A. V. et al. 2023. Comparative pharmacokinetics and injection site histopathology in nude mice treated with long-acting buprenorphine formulations. JAALAS 62(2), 147–152.

Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of...

Kim, J., Cannon, B. A., Freeman, L. E. et al. 2023. High-dose meloxicam provides improved analgesia in female CD1 mice: A pharmacokinetic and efficacy study. JAALAS 62(1), 74–80.

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses...