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. 
Klune, C. B., Robbins, H. N. K., Leung, V. et al. 2020. Hypothermia during general anesthesia interferes with pain assessment in laboratory rats (Rattus norvegicus). JAALAS 59(6), 719-725.

Accurate pain assessment methods are necessary to ensure animal welfare and reliable data collection in animal research. The Rat Grimace Scale (RGS), a facial expression pain scale, allows effective identification of pain. However, the potential...

Scarborough, J., Mueller, F., Arban, R. et al. 2020. Preclinical validation of the micropipette-guided drug administration (MDA) method in the maternal immune activation model of neurodevelopmental disorders. Brain, Behavior, and Immunity 88, 461-470.

Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages...

Mogil, J. S., Pang, D. S. J., Silva Dutra, G. G. et al. 2020. The development and use of facial grimace scales for pain measurement in animals. Neuroscience & Biobehavioral Reviews 116, 480-496.

The measurement of pain in animals is surprisingly complex, and remains a critical issue in veterinary care and biomedical research. Based on the known utility of pain measurement via facial expression in verbal and especially...

Woodard, C. L., Nasrallah, W. B., Samiei, B. V. et al. 2020. PiDose: An open-source system for accurate and automated oral drug administration to group-housed mice. Scientific Reports 10, 11584.

Drug treatment studies in laboratory mice typically employ manual administration methods such as injection or gavage, which can be time-consuming to perform over long periods and cause substantial stress in animals. These stress responses may...

Lefebvre, E., Granon, S., Chauveau, F. 2020. Social context increases ultrasonic vocalizations during restraint in adult mice. Animal Cognition 23(2), 351–359.

Adult mice emit many ultrasonic vocalizations (USVs) during social interaction tasks, but only a few studies have yet reported USVs in stressed adult mice. Our aim was to study which experimental conditions favor USV emission...

Ahloy-Dallaire, J., Klein, J. D., Davis, J. K. et al. 2019. Automated monitoring of mouse feeding and body weight for continuous health assessment. Laboratory Animals 53(4), 342–351.

Routine health assessment of laboratory rodents can be improved using automated home cage monitoring. Continuous, non-stressful, objective assessment of rodents unaware that they are being watched, including during their active dark period, reveals behavioural and...

Resasco, A., Carranza Martin, A. C., Ayala, M. A. et al. 2019. Non-aversive photographic measurement method for subcutaneous tumours in nude mice. Laboratory Animals 53(4), 352–361.

We have developed a new method for the measurement of subcutaneous tumour volume which consists in taking photographs of mice in their home cages, to refine the standard method of measurement with calipers. We consider...

Balansard, I., Cleverley, L., Cutler, K. L. et al. 2019. Revised recommendations for health monitoring of non-human primate colonies (2018): FELASA Working Group Report. Laboratory Animals 53(5), 429–446.

The genetic and biological similarity between non-human primates and humans has ensured the continued use of primates in biomedical research where other species cannot be used. Health-monitoring programmes for non-human primates provide an approach to...

Bauer, C., Schillinger, U., Brandl, J. et al. 2019. Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice. Laboratory Animals 53(5), 459–469.

In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to...

Gjendal, K., Lund Ottesen, J., Olsson, I. A. S. et al. 2019. Burrowing and nest building activity in mice after exposure to grid floor, isoflurane or ip injections. Physiology & Behavior 206, 59-66.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the...

Redaelli, V., Papa, S., Marsella, G. et al. 2019. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury. PLOS ONE 14(10), e0224337.

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord...

Klune, C. B., Larkin, A. E., Leung, V. S. Y. et al. 2019. Comparing the Rat Grimace Scale and a composite behaviour score in rats. PLOS ONE 14(5), e0209467.

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression...

Broche Jr., N., Takeshita, R. S. C., Mouri, K. et al. 2019. Salivary alpha-amylase enzyme is a non-invasive biomarker of acute stress in Japanese macaques (Macaca fuscata). Primates volume 60(6), 547–558.

Salivary alpha-amylase (sAA) enzyme functions as a digestive enzyme in many species that consume starch in their diet. Human studies have also revealed that sAA enzyme activity levels are positively correlated with the release of...

Campos-Luna, I., Miller, A., Beard, A. et al. 2019. Validation of mouse welfare indicators: A Delphi consultation survey. Scientific Reports 9, 10249.

This study aims to identify the most valid, reliable and practicable indicators of laboratory mouse welfare using the Delphi consultation technique. The effective assessment of laboratory mouse welfare is a fundamental legal and moral requirement...

Poirier, C., Oliver, C. J., Castellano Bueno, J. et al. 2019. Pacing behaviour in laboratory macaques is an unreliable indicator of acute stress. Scientific Reports 9, 7476.

Pacing behaviour, the most frequent stereotypic behaviour displayed by laboratory rhesus macaques (Macaca mulatta) is often used as an indicator of stress. In this study, we investigated how reliable this welfare indicator is at detecting...

Abdelrahman, A., Kumstel, S., Zhang, X. et al. 2019. A novel multi-parametric analysis of non-invasive methods to assess animal distress during chronic pancreatitis. Scientific Reports 9, 14084.

Ethical responsibility, legal requirements and the need to improve the quality of research create a growing interest in the welfare of laboratory animals. Judging the welfare of animals requires readout parameters, which are valid and...

Cox, R. J., Nol, P., Ellis, C. K. et al. 2019. Research with agricultural animals and wildlife. ILAR Journal 60(1), 66-73.

In fiscal year 2016, agricultural animals such as swine, sheep, goats, and cattle represented 10% of the 820 812 animals used in USDA-regulated research. In addition to traditional agricultural animals, research studies using captive wildlife...

Ritchie, A., Collier, P., Clare, P. et al. 2019. Food for thought: The development of drug loaded diets improve both science and welfare. Animal Technology and Welfare 18(3), 222-224.

In our facility, we use several hormone dependent tumour models with supplementation delivered via slow release subcutaneously implanted pellets, implanted via trochar. For example, breast tumours which rely on 17-β-Estradiol. Administration of E2 supplementation can...

Smith, B. J., Bruner, K., Kendall, L. V. 2019. Female- and intruder-induced ultrasonic vocalizations in C57BL/6J mice as proxy indicators for animal wellbeing. Comparative Medicine 69(5), 374–383.

Female urine-induced male mice ultrasonic vocalizations (FiUSV) are ultrasonic vocalizations produced by adult male mice after presentation of adult female urine, whereas intruder-induced ultrasonic vocalizations (IiUSV) are produced by resident adult female mice when interacting...

Jirkof, P., Rudeck, J., Lewejohann, L. 2019. Assessing affective state in laboratory rodents to promote animal welfare—What is the progress in applied refinement research? Animals 9(12), 1026.

In the past, there was a strong focus on avoiding or reducing negative animal welfare in animal experimentation. Recently, the importance of promoting positive animal welfare in laboratory animals has been highlighted. To ensure and...

Rowland, N. E., Toth, L. A. 2019. Analytic and interpretational pitfalls to measuring fecal corticosterone metabolites in laboratory rats and mice. Comparative Medicine 69(5), 337–349.

Minimization and alleviation of stress are generally viewed as desirable aspects of laboratory animal management and use. However, achieving that goal requires an unambiguous and valid measure of stress. Glucocorticoid concentrations are commonly used as...

McMillan, F. D. (ed). 2019. Mental Health and Well-being in Animals (2nd ed). CABI, Wallingford, UK.

This second edition is fully revised, expanded, and comprehensively updated with the most current knowledge about the full array of mental health issues seen in animals. Written by key opinion leaders, internationally-recognized experts and specialists...

Descovich, K. A., Richmond, S. E., Leach, M. C. et al. 2019. Opportunities for refinement in neuroscience: Indicators of wellness and post-operative pain in laboratory macaques. Alternatives to Animal Experimentation 36(4), 535-554.

Being able to assess pain in nonhuman primates undergoing biomedical procedures is important for preventing and alleviating pain, and for developing better guidelines to minimize the impacts of research on welfare in line with the...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

Mason, S., Premereur, E., Pelekanos, V. et al. 2019. Effective chair training methods for neuroscience research involving rhesus macaques (Macaca mulatta). Journal of Neuroscience Methods 317, 82-93.

Background: Neuroscience research using macaques remains fundamental in our endeavours to understand how the human brain functions. Applying the refinement principle of the 3Rs is essential to optimise the monkeys’ welfare and still produces high...