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...

Lucrezia Costa, G., Nastasi, B., Spadola, F. et al. 2019. Effect of levobupivacaine, administered intraperitoneally, on physiological variables and on intrasurgery and postsurgery pain in dogs undergoing ovariohysterectomy. Journal of Veterinary Behavior 30, 33-36.

The aim of this study was to evaluate intraoperative and postoperative efficacy and cardiovascular effects of levobupivacaine compared with bupivacaine, administered intraperitoneally in dogs undergoing ovariohysterectomy surgery. Thirty female dogs were divided into three groups...

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...

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...

Evangelista-Vaz, R., Bergadano, A., Arras, M. et al. 2018. Analgesic efficacy of subcutaneous–oral dosage of tramadol after surgery in C57BL/6J mice. JAALAS 57(4), 368-375.

This study investigated the analgesic activity of tramadol in female C57BL/6J mice by using a single subcutaneous injection (25 mg/kg) of tramadol combined with the same dose given in drinking water for 24 h. We...

Beninson, J. A., Lofgren, J. L., Lester, P. A. et al. 2018. Analgesic efficacy and hematologic effects of robenacoxib in mice. JAALAS 57(3), 258-267.

NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Galvin, M., Lallo, A., Brown, S. et al. 2018. Refinement of tumour passage by optimisation of the tissue disaggregation protocol. Animal Technology and Welfare 17(2), 101-103.

Surgical implantation of tumour pieces has been used regularly in the passage of tumour models. This involves an invasive surgical procedure, carried out under anaesthesia, ensuring mice have adequate pain relief and peri-operative care. The...

Beamish, G., Chapman, C., Lomax, A. 2018. Design by intravenous injection in the Syrian hamster. Animal Technology and Welfare 17(2), 124-125.

Repeated injections in rats and mice are typically done via the tail vein. For hamsters, the tail is not an option. In this paper we explore the development and refinement of IV dosing in the...

Jirkof, P., Arras, M., Cesarovic, N. 2018. Tramadol:Paracetamol in drinking water for treatment of post-surgical pain in laboratory mice. Applied Animal Behaviour Science 198, 95-100.

In the search for stress-free analgesia administration for laboratory mice suffering pain, oral delivery of Tramadol:Paracetamol (T:P) shows great promise. Here, we monitored the analgesic efficacy and side effects of a T:P combination administered solely...

Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Torad, F. A., Hassan, E. A. 2018. Sedative, analgesic, and behavioral effects of nalbuphine-xylazine and nalbuphine-midazolam combinations in dogs. Journal of Veterinary Behavior 28, 40-45.

The purpose of the present study was to evaluate the sedative, analgesic, and behavioral effects of nalbuphine-xylazine (NX) and nalbuphine-midazolam (NM) combinations for neuroleptanalgesia in dogs. A prospective randomized crossover study was done on six...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...

Deckers, N., Ruigrok, C. A., Verhoeve, H. P. et al. 2018. Comparison of pain response after subcutaneous injection of two maropitant formulations to beagle dogs. Veterinary Record Open 5(1), e000262.

The antiemetic maropitant, with metacresol as preservative (Cerenia, Zoetis), has been associated with pain after subcutaneous injection in dogs and cats. Recently, a generic formulation containing benzyl alcohol was authorised (Prevomax, Le Vet). Benzyl alcohol...

Kluge, K., Larenza Menzies, M. P., Kloeppel, H. et al. 2017. Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy. Laboratory Animals 51(1), 54-64.

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and...

Tavera-Mendoza, L. E., Brown, M. 2017. A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland. Laboratory Animals 51(1), 85-88.

Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an...

Larsen, R. A., Peveler, J. L., Klutzke, J. B. et al. 2017. Effects of daily restraint with and without injections on skeletal properties in C57BL/6NHsd mice. Lab Animal 46(7), 299-301.

Studies typically involve groups of animals that are injected with placebo compounds. As there are studies that demonstrate that restraint and injection can affect behavior and corticosteroid levels in rodents, the basis of such placebo...

Jirkof, P. 2017. Side effects of pain and analgesia in animal experimentation. Lab Animal 46(4), 123-128.

This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

Hubbard, J. S., Chen, P. H., Boyd, K. L. 2017. Effects of repeated intraperitoneal injection of pharmaceutical-grade and nonpharmaceutical-grade corn oil in female C57BL/6J mice. JAALAS 56(6), 779-785.

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...