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. 
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...

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...

Egelkamp, C. L., Ross, S. R. 2019. A review of zoo-based cognitive research using touchscreen interfaces. Zoo Biology 38(2), 220-235.

In the past few decades, there has been an increase in the number of zoo-based touchscreen studies of animal cognition around the world. Such studies have contributed to the field of comparative cognition despite the...

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...

Tuttle, A. H., Molinaro, M. J., Jethwa, J. F. et al. 2018. A deep neural network to assess spontaneous pain from mouse facial expressions. Molecular Pain 14, 1-9.

Grimace scales quantify characteristic facial expressions associated with spontaneous pain in rodents and other mammals. However, these scales have not been widely adopted largely because of the time and effort required for highly trained humans...

Oliver, V. L., Thurston, S. E., Lofgren, J. L. 2018. Using cageside measures to evaluate analgesic efficacy in mice (Mus musculus) after surgery. JAALAS 57(2), 186-201.

Recent studies have revealed some of the most frequently used analgesics in mice are not effectively treating postoperative pain. Our laboratory sought to compare and assess the validity and reliability of 2 cageside pain assessments...

Mei, J., Riedel, N., Grittner, U. et al. 2018. Body temperature measurement in mice during acute illness: Implantable temperature transponder versus surface infrared thermometry. Scientific Reports 8, 3526.

Body temperature is a valuable parameter in determining the wellbeing of laboratory animals. However, using body temperature to refine humane endpoints during acute illness generally lacks comprehensiveness and exposes to inter-observer bias. Here we compared...

Chotard, H., Ioannou, S., Davila-Ross, M. 2018. Infrared thermal imaging: Positive and negative emotions modify the skin temperatures of monkey and ape faces. American Journal of Primatology 80(5), e22863.

Facial thermography has enabled researchers to noninvasively and continuously measure the changes of a range of emotional states in humans. The present work used this novel technology to study the effect of positive and negative...

Pomerantz, O., Nyandwi, S., Baker, K., 2018. Providing feeding enrichment by hand mitigates anxiety among laboratory-housed rhesus macaques (Macaca mulatta). American Journal of Primatology 80(S1), 20 (40th Meeting of the American Society of Primatologists Scientific Program, Abstract #26).

Some husbandry procedures may be perceived as aversive by cage‐housed rhesus macaques. We assessed whether providing feeding enrichment by hand as opposed to placing it on a caging surface decreases anxiety responses to daily husbandry...

Fiebig, K., Jourdan, T., Kock, M. H. et al. 2018. Evaluation of infrared thermography for temperature measurement in adult male NMRI nude mice. JAALAS 57(6), 715–724.

Temperature monitoring during critical care provides important data required to guide treatment delivery. Body temperature is an easily quantified clinical parameter that can yield much information concerning the health of an animal. In research settings...

Neely, C., Lane, C., Torres, J. et al. 2018. The effect of gentle handling on depressive-like behavior in adult male mice: Considerations for human and rodent interactions in the laboratory. Behavioural Neurology 2018, 2976014.

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being...

Hankenson, F. C., Marx, J. O., Gordon, C. J. et al. 2018. Effects of rodent thermoregulation on animal models in the research environment. Comparative Medicine 68(6), 425–438.

To best promote animal wellbeing and the efficacy of biomedical models, scientific, husbandry, and veterinary professionals must consider the mechanisms, influences, and outcomes of rodent thermoregulation in contemporary research environments. Over the last 2 decades...

Häger, C., Keubler, L. M., Talbot, S. R. et al. 2018. Running in the wheel: Defining individual severity levels in mice. PLOS Biology 16(10), e2006159.

The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly...

Unakafov, A. M., Möller, S., Kagan, I. et al. 2018. Using imaging photoplethysmography for heart rate estimation in non-human primates. PLOS ONE 13(8), e0202581.

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2018. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. PLOS ONE 13(9), e0203559.

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain...

Witham, C. L. 2018. Automated face recognition of rhesus macaques. Journal of Neuroscience Methods 300, 157-165.

Background: Rhesus macaques are widely used in biomedical research. Automated behavior monitoring can be useful in various fields (including neuroscience), as well as having applications to animal welfare but current technology lags behind that developed...