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. 
Valros, A., Norring, M., Ahlqvist, K. et al. 2024. Effects of repeated intramuscular injections on sow behaviour reactions and stress-related saliva biomarkers – A pilot study. Applied Animal Behaviour Science 271, 106173.

Medicating large production animals, such as sows, individually can be challenging, especially when repeated treatments are needed. Intramuscular (i.m.) injections have been shown to be aversive, and an increased reaction could be expected over consecutive...

Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

Bellini, L., Schrank, M., Veladiano, I. A. et al. 2023. Retrospective comparison of the effects of laryngeal mask and endotracheal tube on some cardio-respiratory variables in pet rabbits undergoing anaesthesia for elective gonadectomy. Acta Veterinaria Scandinavica 65(1), 10.

Endotracheal intubation in rabbits is challenging and supraglottic airway devices, such as laryngeal masks (LMA), represent an alternative as they are easy to insert, and do not stimulate the larynx requiring therefore a lighter plane...

Lambertini, C., Grandis, A., De Silva, M. et al. 2023. The spritztube: A new device for extraglottic intubation of rabbits. Animals 13(1), 156.

The Spritztube (ST) is an extraglottic airway device developed for humans. The aim of the study was to design an ST for rabbits and to evaluate its feasibility. The study was divided into two phases...

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...

Miller, R., Grott, A., Patzkéwitsch, D. et al. 2023. Behavior of piglets in an observation arena before and after castration with local anesthesia. Animals 13(3), 529.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

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...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

Elane, G. L., Portela, D. A., Hobbs, K. J. et al. 2023. Sedated cesarean sections are associated with increased kid survival compared to general anesthesia in goats: Retrospective cohort of 45 cases (2011–2021). Journal of the American Veterinary Medical Association 261(3), 391–396.

OBJECTIVE To determine whether anesthesia type (sedation or general anesthesia) affects kid survival to discharge in caprine cesarean sections (C-sections). ANIMALS Retrospective cohort of 99 caprine C-sections (2011–2021). PROCEDURES All surgeries were performed via left...

Martin-Flores, M., Nugen, S. A., Boesch, J. M. et al. 2023. Low-dose epidural anesthesia decreases the use of intraoperative systemic analgesics in goats undergoing lower urinary tract surgery. Journal of the American Veterinary Medical Association 261(8), 1147–1151.

OBJECTIVE To test whether the use of low-dose epidural anesthesia (EA) in goats undergoing lower urinary tract surgery reduces the requirements of perioperative analgesics, contributes to intraoperative hypotension, and improves postoperative comfort during the first...

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...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Guerrero-Martin, S. M., Brill, S., Carlson, B. W. 2022. Development and implementation of a positive reinforcement training program for nonhuman primates in biomedical research. Laboratory Animal Science Professional 10(1) (January/February), 48-52.

Despite clear benefits of PRT for NHPs and biomedical research, investigators often view the investment in personnel expertise and time required to train animals as deterrents towards adopting PRT. We provide an example of how...

Coutant, M., Malmkvist, J., Kaiser, M. et al. 2022. Piglets’ acute responses to local anesthetic injection and surgical castration: Effects of the injection method and interval between injection and castration. Frontiers in Veterinary Science 9, 1009858.

Although applied in some countries, efficacy of local anesthetics based on procaine to mitigate acute responses to piglet castration remains questioned. This paper presents results from a factorial study examining the effects of two methods...

Söbbeler, F. J., Wendt, S., Briese, A. et al. 2022. Comparative study of pain-related responses of male piglets up to seven days of age to the application of different local anaesthetics and subsequent castration. Animals 12(20), 2833.

To evaluate pain responses to intratesticular and subscrotal injection of three local anaesthetics and their efficacy during castration a randomized controlled study was conducted. In groups of 20 piglets, procaine (2%), lidocaine (2%), or mepivacaine...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Skade, L., Kristensen, C. S., Nielsen, M. B. F. et al. 2021. Effect of two methods and two anaesthetics for local anaesthesia of piglets during castration. Acta Veterinaria Scandinavica 63, 1.

Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the “Danish quality scheme”; a voluntary initiative taken by the...

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...

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...

Haertel, A. J., Schultz, M. A., Colgin, L. M. et al. 2021. Predictors of subcutaneous injection site reactions to sustained-release buprenorphine in rhesus macaques (Macaca mulatta). JAALAS 60(3), 329-336.

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaques have been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors of buprenorphine SR...

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...

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...