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. 
Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

Trujanovic, R., Rohrbach, H. 2023. Ultrasound-guided block of the sciatic and the femoral nerves in rabbits—A descriptive anatomical study. Animals 13(14), 2393.

The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their...

Miller, A. L., Clarkson, J. M., Quigley, C. et al. 2022. Evaluating pain and analgesia effectiveness following routine castration in rabbits using behavior and facial expressions. Frontiers in Veterinary Science 9, 782486.

Prevention of pain in rabbits is a priority for both welfare and validity of scientific data. We aimed to determine if the rabbit grimace scale (RbtGS) could be used as a viable, rapid assessment tool...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Paterson, E. A., Turner, P. V. 2022. Challenges with assessing and treating pain in research primates: A focused survey and literature review. Animals 12(17), 2304.

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and...

Windsor, P. A. 2022. Role of topical anaesthesia in pain management of farm animals, a changing paradigm. Animals 12(18), 2459.

Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more recently, viral epidermal infectious diseases, including FMD. There has been impressive adoption in...

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...

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...

Camargo-dos-Santos, B., Carlos, C. L., Favero-Neto, J. et al. 2021. Welfare in Nile tilapia production: Dorsal fin erection as a visual indicator for insensibility. Animals 11(10), 3007.

In aquaculture, to ensure animal welfare in pre-slaughter and slaughter stages, it is fundamental that fish are insensible. A method for evaluating fish insensibility is based on visual sensibility indicators (VSI) assessment (i.e., self-initiated behavior...

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...

Ajuda, I., Battini, M., Mattiello, S. et al. 2020. Evaluation of pain mitigation strategies in goat kids after cautery disbudding. Animals 10(2), 277.

Nowadays, most of the goat milk production in developed countries is done in intensive indoors production systems. In these systems, procedures such as disbudding are performed routinely. Disbudding is done in young goat kids and...

Bertho, J.-M., Ancelet, S., Denais-Laliève, D. et al. 2020. Humane endpoints in severe irradiation experiments using non-human primates: A retrospective analysis. Scandinavian Journal of Laboratory Animal Science 46(1).

A retrospective statistical study has been performed in order to identify the biological, clinical and behavioural variables that could potentially predict the survival status of irradiated non-human primates (NHP) and to refine the future use...

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...

Hempstead, M. N., Waas, J. R., Stewart, M. et al. 2020. Goat kids are not small calves: Species comparisons in relation to disbudding. Animal Welfare 29(3), 293-312.

Limited scientific literature is available for developing 'best practices' guidelines for the management of dairy goats (Caprus hircus), particularly goat kids. Disbudding practices for kids and calves appear to be similar, however, it is important...

Hempstead, M. N., Waas, J. R., Stewart, M. et al. 2020. Can isoflurane and meloxicam mitigate pain associated with cautery disbudding of 3-week-old goat kids? Animals 10(5), 878.

We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does (mean ± SD, 21 ± 3 days old) were randomly allocated...

Hempstead, M. N., Lindquist, T. M., Shearer, J. K. et al. 2020. Acute cortisol and behavior of dairy goat kids administered local anesthesia, topical anesthesia or systemic analgesia prior to cautery disbudding. Physiology & Behavior 222, 112942.

Cautery disbudding of goat kids causes thermal burns and tissue destruction, which results in acute and post-operative pain and negatively affects animal welfare. The objectives of this study were to evaluate acute cortisol concentrations and...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Frahm, S., Di Giminiani, P., Stanitznig, A. et al. 2020. Nociceptive threshold of calves and goat kids undergoing injection of clove oil or isoeugenol for disbudding. Animals 10(7), 1228.

In this preliminary study, we compared changes in mechanical nociceptive thresholds (MNT) of calves and goat kids injected with clove oil or isoeugenol under the horn bud as a potential, more welfare-friendly alternative to hot-iron...

Eshar, D., Beaufrère, H. 2020. Anesthetic effects of alfaxalone–ketamine, alfaxalone–ketamine–dexmedetomidine, and alfaxalone–butorphanol–midazolam administered intramuscularly in five striped palm squirrels (Funambulus pennantii). JAALAS 59(4), 384-392.

Injectable anesthesia protocols for five striped palm squirrels (Funambulus pennantii) are poorly described in the literature. In this study, male intact squirrels received intramuscular injections of either alfaxalone (6 mg/kg) and ketamine (40 mg/ kg...

Ambar, N., Eshar, D., Shrader, T. C. et al. 2020. Anesthetic effects of intramuscular alfaxalone–ketamine in naked mole rats (Heterocephalus glaber). JAALAS 59(5), 539-545.

In this study, adult intact male and female (n = 10) naked mole rats (Heterocephalus glaber) were anesthetized by using a combination of ketamine (20 mg/kg IM), and alfaxalone (4.0 mg/kg IM). Induction and recovery...

Andrews, D. D., Fajt, V. R., Baker, K. C. et al. 2020. A comparison of buprenorphine, sustained release buprenorphine, and high concentration buprenorphine in male New Zealand white rabbits. JAALAS 59(5), 546-556.

Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could...

Musk, G. C., Ezzy, B. J., Kenchington, L. M. et al. 2020. A comparison of buffered tricaine methanesulfonate (MS-222) and isoeugenol anesthesia for caudal fin clipping in zebrafish (Danio rerio). JAALAS 59(6), 732-736.

The purpose of this study was to compare the safety and efficacy of buffered tricaine methanesulfonate (MS-222) and isoeugenol for the anesthesia of zebrafish undergoing caudal fin clipping. Eighty 9 mo Danio rerio (AB strain)...

Raillard, M., Detotto, C., Grepper, S. et al. 2019. Anaesthetic and perioperative management of 14 male New Zealand white rabbits for calvarial bone surgery. Animals 9(11), 896.

Calvarial bone surgery on rabbits is frequently performed. This report aims to document a simple and practical anaesthetic and perioperative management for this procedure. Fourteen male New Zealand white rabbits were included in the study...

Krall, C., Glass, S., Dancourt, G. et al. 2019. Behavioural anxiety predisposes rabbits to intra-operative apnoea and cardiorespiratory instability. Applied Animal Behaviour Science 221, 104875.

Rabbits are prone to complications from both anaesthesia and anxiety. Given that anxiety can often impact quality of anaesthesia, we developed a novel cage-side anxiety assessment, and sought to determine whether it correlated to pre-...