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. 
Kendall, L. V., Singh, B., Bailey, A. L. et al. 2021. Pharmacokinetics and efficacy of a long-lasting, highly concentrated buprenorphine solution in mice. JAALAS 60(1), 64-71.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate...

Schalbetter, S. M., Mueller, F. S., Scarborough, J. et al. 2021. Oral application of clozapine-N-oxide using the micropipette-guided drug administration (MDA) method in mouse DREADD systems. Lab Animal 50, 69-75.

The designer receptor exclusively activated by designer drugs (DREADD) system is one of the most widely used chemogenetic techniques to modulate the activity of cell populations in the brains of behaving animals. DREADDs are activated...

Teixeira-Santos, L., Albino-Teixeira, A., Pinho, D. 2021. An alternative method for oral drug administration by voluntary intake in male and female mice. Laboratory Animals 55(1), 76-80.

Drug administration to experimental rodents is often invasive and stressful, thus reducing animal welfare and potentially confounding experimental results. Methods of oral drug delivery in which rodents cooperate voluntarily minimize stress, pain and morbidity. We herein...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Stevens, C., Hawkins, P., Smulders, T. V. et al. 2021. Report of the 2020 RSPCA/UFAW rodent and rabbit welfare meeting. Animal Technology and Welfare 20(1), 21-33.

The RSPCA/UFAW rodent and rabbit welfare group has held a one-day meeting every autumn for the last 27 years, so that its members can discuss current welfare research, exchange views on welfare issues and share...

Manell, E., Hedenqvist, P., Jensen-Waern, M. 2021. Training pigs for oral glucose tolerance test—Six years’ experience of a refined model. Animals 11(6), 1677.

Animal models of human diseases are important in biomedical research. When using animals for scientific purposes, the 3Rs (replace, reduce, refine) should be considered. Refinement of animal models is essential to ensure best use of...

Steagall, P. V., Bustamante, H., Johnson, C. B. et al. 2021. Pain management in farm animals: Focus on cattle, sheep and pigs. Animals 11(6), 1483.

Pain causes behavioral, autonomic, and neuroendocrine changes and is a common cause of animal welfare compromise in farm animals. Current societal and ethical concerns demand better agricultural practices and improved welfare for food animals. These...

Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...

Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...

Chang, L.-J., Ko, J. C., Weil, A. B. et al. 2021. Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol, tiletamine-zolazepam-xylazine-butorphanol, and ketamine-detomidine-butorphanol in pigs. Journal of the AVMA 258(8), 883-891.

OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Sheil, M., De Benedictis, G. M., Scollo, A. et al. 2021. Efficacy of intra-operative topical wound anaesthesia to mitigate piglet castration pain—A large, multi-centred field trial. Animals 11(10), 2763.

Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

Schmid, S. M., Steinhoff-Wagner, J. 2021. Behavior and body temperature alterations in piglets anesthetized for castration during a four-hour recovery phase. Applied Animal Behaviour Science 245, 105497.

One way to eliminate pain during surgical castration is to provide general anesthesia by intramuscular injection. However, its disadvantage is the long recovery phase, during which anesthetized piglets have to be separated from the sow...

Kinaci, A., Vaessen, K., Redegeld, S. et al. 2021. Minimizing complications in a porcine survival craniotomy model. Laboratory Animals 55(5), 435-442.

A large craniotomy survival porcine model is useful for scientific research. The surgical approaches and complications of craniotomies in pigs have not been published before. This study describes how large craniotomies were performed in 46...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Jorge, S., Ferreira, J. M., Olsson, I. A. S. et al. 2021. Efficacy and behavioral recovery of different anesthetics. Zebrafish 18(5), 330-337.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality...

Furumoto, K., Ogita, K., Kamisaka, T. et al. 2021. Effects of multimodal analgesic protocol, with buprenorphine and meloxicam, on mice well-being: A dose finding study. Animals 11(12), 3420.

The anesthetic or analgesic agent of choice, route and frequency of anesthetic or analgesic administration, and stressors induce distress during the perioperative period. We evaluated a multimodal analgesic protocol using buprenorphine and meloxicam on the...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...

Lervik, A., Toverud, S. F., Krontveit, R. et al. 2020. A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine. Acta Veterinaria Scandinavica 62(1), 1-9.

Background: General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory...

Burkemper, M. C., Pairis-Garcia, M. D., Moraes, L. E. et al. 2020. Effects of oral meloxicam and topical lidocaine on pain associated behaviors of piglets undergoing surgical castration. Journal of Applied Animal Welfare Science 23(2), 209-218.

The objective of this study was to find a practical means of reducing pain associated with surgical castration by evaluating the effects of oral meloxicam and topical lidocaine, separately and in combination, on behavioral indicators...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Nøgaard, S. A., Sand, F. W., Sørensen, D. B. et al. 2020. Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice. Animal Welfare 29(2), 143-149.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Whittaker, A. L., Barker, T. H. 2020. The impact of common recovery blood sampling methods, in mice (Mus musculus), on well-being and sample quality: A systematic review. Animals 10(6), 989.

Blood sampling is often performed in laboratory mice. Sampling techniques have the potential to cause pain, distress and impact on lifetime cumulative experience. In spite of institutions commonly providing guidance to researchers on these methods...