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. 
Turner, P. V., Pang, D. S., Lofgren, J. L. 2019. A review of pain assessment methods in laboratory rodents. Comparative Medicine 69(6), 451–467.

Ensuring that laboratory rodent pain is well managed underpins the ethical acceptability of working with these animals in research. Appropriate treatment of pain in laboratory rodents requires accurate assessments of the presence or absence of...

Foley, P. L., Kendall, L. V., Turner, P. V. 2019. Clinical management of pain in rodents. Comparative Medicine 69(6), 468–489.

The use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. Factors contributing to this gap...

Smith J. C. 2019. A review of strain and sex differences in response to pain and analgesia in mice. Comparative Medicine 69(6), 490–500.

Pain and its alleviation are currently a highly studied issue in human health. Research on pain and response to analgesia has evolved to include the effects of genetics, heritability, and sex as important components in...

Gjendal, K., Ottesen, J. L., Olsson, I. et al. 2020. Effect of repeated exposure to isoflurane on nest building and burrowing in mice. JAALAS 59(1), 30–36.

Nest building and burrowing are highly motivated natural behaviors in rodents, and changes in these behaviors can serve as welfare assessment tools. In this study, we investigated: 1) the limits of agreement between 2 observers...

Gallo, M. S., Karas, A. Z., Pritchett-Corning, K. et al. 2020. Tell-tale TINT: Does the time to incorporate into nest test evaluate postsurgical pain or welfare in mice? JAALAS 59(1), 37–45.

Identifying early indicators of distress in mice is difficult using either periodic monitoring or current technology. Likewise, poor pain identification remains a barrier to providing appropriate pain relief in many mouse models. The Time to...

Nwagwu, C. D., Defensor, E., Jiang, M. Y. et al. 2020. Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics. Lab Animal 49(8), 227–232.

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective...

Wilkinson, M. J. A., Selman, C., McLaughlin, L. et al. 2020. Progressing the care, husbandry and management of ageing mice used in scientific studies. Laboratory Animals 54(3) 225–238.

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with...

Nørgaard, S. A., Søndergaard, H., Sørensen, D. B. et al. 2020. Optimising streptozotocin dosing to minimise renal toxicity and impairment of stomach emptying in male 129/Sv mice. Laboratory Animals 54(4), 341–352.

The streptozotocin (STZ)-induced diabetic mouse model has been extensively used as a model for diabetes and diabetic nephropathy, but it is still influenced by many off-target toxic effects and large variation in diabetes induction. Therefore...

Kersemans, V., Wallington, S., Allen, P. D. et al. 2020. Manganese-free chow, a refined non-invasive solution to reduce gastrointestinal signal for T1-weighted magnetic resonance imaging of the mouse abdomen. Laboratory Animals 54(4), 353–364.

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T1 and T2...

Morello, G. M., Hultgren, J., Capas-Peneda, S. et al. 2020. High laboratory mouse pre-weaning mortality associated with litter overlap, advanced dam age, small and large litters. PLOS ONE 15(8): e0236290.

High and variable pre-weaning mortality is a persistent problem in laboratory mouse breeding. Assuming a modest 15% mortality rate across mouse strains, means that approximately 1 million more pups are produced yearly in the EU...

Hohlbaum, K., Frahm, S., Rex, A. et al. 2020. Social enrichment by separated pair housing of male C57BL/6JRj mice. Scientific Reports 10, 11165.

Laboratory male mice are often housed individually due to aggressive behavior or experimental requirements, though social isolation can cause welfare issues. As a strategy to refine housing of male mice, we introduce the separated pair...

Bailoo, J. D., Voelkl, B., Varholick, J. et al. 2020. Effects of weaning age and housing conditions on phenotypic differences in mice. Scientific Reports 10, 11684.

Poor reproducibility is considered a serious problem in laboratory animal research, with important scientific, economic, and ethical implications. One possible source of conflicting findings in laboratory animal research are environmental differences between animal facilities combined...

Zhang, X., Kumstel, S., Tang, G. et al. 2020. A rational approach of early humane endpoint determination in a murine model for cholestasis. ALTEX 37(2), 197-207.

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of...

Blok, J., Black, D. A., Petersen, J. et al. 2020. Environmental enrichment rescues visually-mediated behavior in Ten-m3 knockout mice during an early critical period. Frontiers in Behavioral Neuroscience 14, 22.

Environmental enrichment (EE) has been shown to promote neural plasticity. Its capacity to induce functional repair in models which exhibit profound sensory deficits due to aberrant axonal guidance has not been well-characterized. Ten-m3 knockout (KO)...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

Feige-Diller, J., Krakenberg, V., Bierbaum, L. et al. 2020. The effects of different feeding routines on welfare in laboratory mice. Frontiers in Veterinary Science 6, 479.

The accepted norm in most laboratories around the globe is feeding laboratory mice an ad libitum diet, although several health impairments are well-established. In contrast, reducing the animals' body weight by feeding them less food...

Tang, W., Zillmann, U., Sprengel, R. 2020. Alternative anesthesia of neonatal mice for global rAAV delivery in the brain with non-detectable behavioral interference in adults. Frontiers in Behavioral Neuroscience 14, 115.

Viral-transduced gene expression is the current standard for cell-type-specific labeling and cell tacking in experimental neuroscience. To achieve widespread gene expression, a viral delivery method to neonatal rodents was introduced more than two decades ago...

Bengtsson, C., Eriksson, M. 2020. Handling and training of mice and rats results in calmer animals during experimental procedures. AWI Quarterly 69(2) Summer, 6-8.

This article describes the handling and training protocols for mice and rats in preparation for their use in toxicology studies at the Research Institutes of Sweden (RISE).

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Stevens, C., Finnegan, E., Clarkson, J. et al. 2020. Report of the 2019 RSPCA/UFAW Rodent Welfare meeting. Animal Technology and Welfare 19(2), 101-111.

The RSPCA/UFAW Rodent Welfare Group has held a one-day meeting every autumn for the last 26 years, so that its members can discuss current welfare research, exchange views on welfare issues, and share experiences of...

Singleton, S., Nefla, M., Dennison, N. et al. 2020. Assessing pain in models of rheumatoid arthritis. Animal Technology and Welfare 19(2), 149-152.

A hallmark symptom of rheumatoid arthritis in humans is painful swollen joints. Pain can manifest before any inflammation is noticeable as well as persist long after inflammation has resolved. In rodent models of arthritis, ankle...

Jones, H., King, R. 2020. Refinements to health monitoring. Animal Technology and Welfare 19(2), 153-154.

This poster offers two visual health monitoring scoring sheets for mice. The first consists of a red-amber-green coding system to determine the frequency of daily health checks and when a humane endpoint is reached. The...

Hoskins, S., Brown, J. 2020. Oestrus checking – increasing productivity and embracing the 3R’s. Animal Technology and Welfare 19(2), 159-161.

Much like the menstrual cycle in humans, mice also have a cycle where the eggs ripen, ovulation takes place, the females come into heat and are receptive to mate with the male; this occurs over...

Smith, B. J., Bruner, K., Hess, A. M. et al. 2020. Female urine-induced ultrasonic vocalizations in male C57BL/6J mice as a proxy indicator for postoperative pain. JAALAS 59(2), 204–211.

Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice produce ultrasonic vocalizations after exposure to adult female urine (FiUSV). To determine if FiUSV...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...