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. 
Mills, P. C., Ghodasara, P., Satake, N. et al. 2020. A novel transdermal ketoprofen formulation provides effective analgesia to calves undergoing amputation dehorning. Animals 10(12), 2442.

There is a critical need to ensure that all cattle undergoing surgical husbandry procedures are provided effective pain relief. Non-steroidal anti-inflammatory drugs (NSAIDs) are most commonly used, and typically are administered by intramuscular (IM) injection...

Saville, J. W., Ross, J. A., Trefz, T. et al. 2020. Development and field validation of lidocaine-loaded castration bands for bovine pain mitigation. Animals 10(12), 2363.

Castration is among the most common management procedures performed in the dairy and beef cattle industries and is mainly performed by surgery or elastic banding. Despite the various benefits of castration, all methods produce pain...

Van der Saag, D., Lomax, S., Windsor, P. A. et al. 2019. Effect of lignocaine and a topical vapocoolant spray on pain response during surgical castration of beef calves. Animals 9(4), 126.

This study assessed the efficacy of pre-operative injected lignocaine and peri-operative topical vapocoolant spray, administered as most practical for incorporation into routine calf castration procedures. Calves were randomly allocated to: (1) sham castration (SHAM); (2)...

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...

Gladden, N., Ellis, K., Martin, J. et al. 2019. A single dose of ketoprofen in the immediate postpartum period has the potential to improve dairy calf welfare in the first 48 h of life. Applied Animal Behaviour Science 212, 19-29.

The welfare impact of birth on newborn calves has rarely been studied. Dystocia in particular may have significant welfare costs for calves. While analgesia is sometimes provided to calves born to difficult parturition by veterinary...

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...

Ede, T., von Keyserlingk, M. A. G., Weary, D. M. 2019. Assessing the affective component of pain, and the efficacy of pain control, using conditioned place aversion in calves. Biology Letters 15(10), 20190642.

Pain in animals is typically assessed using reflexive and physiological responses. These measures allow inferences regarding nociception but provide little basis for conclusions about the affective component of pain (i.e. how negatively the experience is...

Marti, S., Meléndez, D. M., Pajor, E. A. et al. 2019. Effect of a single dose of subcutaneous meloxicam before knife castration alone or combined with hot-iron branding on scrotal healing, inflammatory response, and behaviour in 2-mo-old beef calves over 42 d post procedure. Canadian Journal of Animal Science 99(1), 179-190.

The objective of this study was to evaluate the effect of a single subcutaneous injection of meloxicam on scrotal healing, inflammatory response, and behaviour in castrated or castrated and branded beef calves for 42 d...

Smith, A. A., Halliday, L. C., Lindeblad, M. O. et al. 2019. Evaluation of analgesic patches in cynomolgus macaques (Macaca fascicularis). JAALAS 58(3), 356-361.

Opioids are widely used in veterinary and human medicine to manage pain. However, there is a paucity of information in the literature regarding the pharmacokinetics of opioid transdermal patches (TDP) in NHP. Therefore, to determine...

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...

Chatigny, F. 2019. The controversy on fish pain: A veterinarian’s perspective. Journal of Applied Animal Welfare Science 22(4), 400-410.

Fish welfare is still a relatively new field. As such, regulations and protocols to ensure fish welfare are currently limited and vary considerably in different jurisdictions. This is in part because of the ongoing controversy...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...

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...

Anders, N., Roth, B., Grimsbø, E. et al. 2019. Assessing the effectiveness of an electrical stunning and chilling protocol for the slaughter of Atlantic mackerel (Scomber scombrus). PLOS ONE 14(9), e0222122.

Inducing unconsciousness in fish using electrical stunning prior to slaughter may improve fish welfare and fillet quality if such practises can be disseminated into wild capture fisheries. The objectives of this study were to: 1)...

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...

Dunford, K., Hakkesteeg, J., Wilson, C. 2019. Stiff as a board: Measuring rigor mortis in zebrafish. Animal Technology and Welfare 18(3), 203-205.

Schedule one killing (S1K) methods require a two-step process: a humane method of death, typically for Zebrafish an anaesthetic overdose and confirmation of death, such as confirmation of rigor mortis. There is widespread variation of...

Thurman, C. E., Rasmussen, S., Prestia, K. A. 2019. Effect of 3 euthanasia methods on serum yield and serum cortisol concentration in zebrafish (Danio rerio). JAALAS 58(6), 823–828.

Zebrafish are an important model in neuroscience and developmental biology and are also an emerging model in hematology and immunology. Little information is available for zebrafish regarding the physiologic impact of different euthanasia methods and...

Van der Saag, D., Lomax, S., Windsor, P. A. et al. 2018. Evaluating treatments with topical anaesthetic and buccal meloxicam for pain and inflammation caused by amputation dehorning of calves. PLOS ONE 13(6), e0198808.

To assess the effects of a topical anaesthetic (TA) and buccal meloxicam (BM) on behaviour, maximum wound temperature and wound morphology following amputation dehorning of beef calves, 50 unweaned Hereford calves were randomly allocated to...

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...

Gilliam, J. N., Woods, J., Hill, J. et al. 2018. Evaluation of the CASH Dispatch Kit combined with alternative shot placement landmarks as a single-step euthanasia method for cattle of various ages. Animal Welfare 27(3), 225-233.

Humane euthanasia of cattle under field conditions presents special challenges for veterinarians and producers. The purpose of this study was to evaluate the effectiveness of the CASH Dispatch Kit captive-bolt system combined with improved shot...

Golledge, H., Carter, E. 2018. Welfare of fish farmed in the EU during transport and at slaughter. Animal Welfare 27(3), 287-288.

This Report, commissioned by the European Commission, summarises the current state of transport and slaughter practices in the aquaculture industry within eleven case-study countries in the European Economic Area (EAA). Comparisons are also made with...

Lofgren, J., Miller, A. L., Shan Lee, C. C. et al. 2018. Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models. Laboratory Animals 52(4), 351-364.

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10...

Shearer, J. 2018. Euthanasia of cattle: Practical considerations and application. Animals 8(4), 57.

Acceptable methods for the euthanasia of cattle include overdose of an anesthetic, gunshot and captive bolt. The use of anesthetics for euthanasia is costly and complicates carcass disposal. These issues can be avoided by use...