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. 
Fitzwater, A., Zhang, L. 2024. A cost-effective restraint method for safer subcutaneous scruff injections and reducing stress in mice and handlers. Laboratory Animal Science Professional 12(1) (January/February), 52-53.

Subcutaneous injection is a vital technique in mouse-based biomedical research. Compared to other injections, the subcutaneous method poses fewer technical challenges and reduces acute toxicity risks due to slower absorption. Several suitable subcutaneous injection sites...

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...

Swan, J., Boyer, S., Westlund, K. et al. 2023. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Frontiers in Behavioral Neuroscience 17, 1109886.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are...

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...

Xu, J. J., Lucero, M. Y., Herndon, N. L. et al. 2023. Comparison of a minimally invasive transthoracic approach and a surgical method for intrapleural injection of tumor cells in mice. Comparative Medicine 73(2), 120–126.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing...

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...

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...

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...

Riddell, D. L., Hyndman, T. H., Bowden, R. S. et al. 2023. Use of a low-calorie flavored gel to facilitate oral self-administration of analgesics in mice. JAALAS 62(2), 163–169.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to...

Yang, P., Hish, G., Lester, P. A. 2023. Comparison of systemic extended-release buprenorphine and local extended-release bupivacaine-meloxicam as analgesics for laparotomy in mice. JAALAS 62(5), 416–422.

Extended-release (ER) local anesthetics can be used in multi-modal analgesia or in situations in which systemic analgesics may alter animal physiology and thus introduce interpretational confounds. In this study, we compared the analgesic efficacy of...

Martins, T., Matos, A. F., Soares, J. et al. 2022. Comparison of gelatin flavors for oral dosing of C57BL/6J and FVB/N mice. JAALAS 61(1), 89-95.

Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture...

Guerrero-Martin, S. M., Brill, S., Carlson, B. W. 2022. Development and implementation of a positive reinforcement training program for nonhuman primates in biomedical research. Laboratory Animal Science Professional 10(1) (January/February), 48-52.

Despite clear benefits of PRT for NHPs and biomedical research, investigators often view the investment in personnel expertise and time required to train animals as deterrents towards adopting PRT. We provide an example of how...

Bartlett, J., Davies, J., Purawijaya, D. et al. 2022. Refinement of handling and dosing methods for rats and mice. Animal Technology and Welfare 21(2), 120-124.

Modified Handling for Mice: Handling mice by gripping the base of the tail has been shown to negatively impact animal welfare by increasing anxiety and aversion to handling. We aimed to refi ne the dosing...

Donaldson-Wing, M. 2022. Medicated jelly as a replacement for injectables and the use of Maropitant to manage itchy skin in mice. Animal Technology and Welfare 21(2), 134-136.

It is desirable to administer drugs by the least invasive route to (1) optimise welfare, (2) reduce the risk of injury to animal handlers and (3) minimise the impact of restraint and transient pain on...

Paterson, E. A., Turner, P. V. 2022. Challenges with assessing and treating pain in research primates: A focused survey and literature review. Animals 12(17), 2304.

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and...

Chan, G., Si, C., Nichols, M. R. et al. 2022. Assessment of the safety and efficacy of pre-emptive use of extended-release buprenorphine for mouse laparotomy. JAALAS 61(4), 381-387.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR...

Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Chesler, K. C., Motz, C. T., Bales, K. L. et al. 2022. Voluntary oral dosing for precise experimental compound delivery in adult rats. Laboratory Animals 56(2), 147-156.

Preclinical drug studies routinely administer experimental compounds to animal models with the goal of minimizing potential adverse events from the procedure. In this study, we assessed the ability to train adult male Long Evans rats...

Neto, T., Faustino-Rocha, A. I., Gil da Costa, R. M. et al. 2022. A quick and low-intensity method for oral administration to large numbers of mice: A possible alternative to oral gavage. Laboratory Animals 56(2), 185-190.

Oral administration of medication to experimental animals is a cause of significant stress. When coupled to animals who are already under strenuous circumstances due to the disease being modelled, there is a significant risk for...

Bissmire, H. 2022. Green clay: Not just for a pretty face. Animal Technology and Welfare 21(3), 242–243.

Mice can be prone to skin lesions for various reasons. Green clay is a non-invvasive method to treat such skin lesions, and does not require veterinary approval or have properties that may interfere with an...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...