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. 
Stewart, L. A., Imai, D. M., Beckett, L. et al. 2020. Injection-site reactions to sustained-release meloxicam in Sprague–Dawley rats. JAALAS 59(6), 726-731.

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable...

Kloefkorn H, Aiani, L. M., Lakhani, A. et al. 2020. Noninvasive three-state sleep-wake staging in mice using electric field sensors. Journal of Neuroscience Methods 344, 108834.

Study Objective: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. Methods: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were...

Cho, C., Michalidis, V., Lecker, I. et al. 2019. Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale. Scientific Reports 9, 359.

Most research laboratories abide by guidelines and mandates set by their research institution regarding the administration of analgesics to control pain during the postoperative period. Unfortunately, measuring pain originating from the head is difficult, making...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Zvarev, C., Baker, S., Patel, D. 2019. Animal handling in containment. Animal Technology and Welfare 18(2), 140-142. (IAT Congress 2018 Poster Presentation)

As Animal Technologists we are constantly looking at refining and enriching the environmental conditions of all our animals to give them both physical exercise and mental stimulation regardless of their size. However, animals can still...

Dutton III, J. W., Artwohl, J. E., Huang, X. et al. 2019. Assessment of pain associated with the injection of sodium pentobarbital in laboratory mice (Mus musculus). JAALAS 58(3), 373-379.

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined...

Moffitt, A. D., Brignolo, L. L., Ardeshir, A. et al. 2019. The role of emotional contagion in the distress exhibited by grouped mice exposed to CO2. JAALAS 58(4), 430-437.

The 2013 AVMA Guidelines for the Euthanasia of Animals recommends a chamber volume displacement rate of 10% to 30% per minute (v/min) when euthanizing small laboratory rodents with CO2. Group euthanasia of mice is a...

McIntosh, M. K., Armitage-Brown, B., Levy, R. 2019. Refinements of equipment and methodology to reduce risk during pole-guided chair transfer of nonhuman primates. JAALAS 58(4), 462-468.

Neurophysiologic studies of NHP commonly involve their transfer from a housing enclosure to a laboratory by using a mobile chair. This transfer should be performed in a manner that is safe and minimizes stress for...

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...

Deninvan Low, D., Leong Peng, J. Z., Tay, Y. Q. et al. 2019. Playtime! Exploring habituation techniques in laboratory rats. Laboratory Animal Science Professional 7(4) (December), 42-45.

Our rat training program teaches the standard method of handling and restraining that involves picking the rat up by the base of the tail and placing it on the wire mesh to be restrained. We...

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...

Franco, N. H., Gerós, A., Oliveira, L. et al. 2019. ThermoLabAnimal – A high-throughput analysis software for non-invasive thermal assessment of laboratory mice. Physiology & Behavior, 207, 113-121.

Body temperature changes in laboratory mice are often assessed by invasive and stressful methods, which may confound the measurement. Infrared thermography is a possible non-invasive alternative, but the cost of standard thermal cameras, lack of...

Mertens, S., Vogt, M. A., Gass, P. et al. 2019. Effect of three different forms of handling on the variation of aggression-associated parameters in individually and group-housed male C57BL/6NCrl mice. PLOS ONE 14(4), e0215367.

Mice are social animals hence group-housing of mice is preferred over individual housing. However, aggression in group-housed male mice under laboratory housing conditions is a well-known problem leading to serious health issues, including injury or...

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...

Gouveia, K., Hurst, J. L. 2019. Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice. Scientific Reports 9, 20305.

Handling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

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...

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...

Narayan, E., Perakis, A., Meikle, W. 2019. Using thermal imaging to monitor body temperature of koalas (Phascolarctos cinereus) in a zoo setting. Animals 9(12), 1094.

Non-invasive techniques can be applied for monitoring the physiology and behaviour of wildlife in Zoos to improve management and welfare. Thermal imaging technology has been used as a non-invasive technique to measure the body temperature...

Doerning, C. M., Thurston, S. E., Villano, J. S. et al. 2019. Assessment of mouse handling techniques during cage changing. JAALAS 58(6), 767–773.

Mouse handling during cage changing and health evaluation has traditionally been performed by using forceps. This method was adopted as a biosecurity measure but can adversely affect employee ergonomics and rodent behavior. In this study...

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...

Skinner, M., Ceuppens, P., White, P. et al. 2019. Social-housing and use of double-decker cages in rat telemetry studies. Journal of Pharmacological and Toxicological Methods 96, 87-94.

Rat telemetry is widely used for biomedical research purposes and is used routinely in early pre-clinical drug development to screen for the potential cardiovascular risk of candidate drugs. Historically, these studies have been conducted in...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...