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. 
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...

Eeza, M. N. H., Singer, R., Ding, Y. et al. 2023. Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging. PLOS ONE 18(4), e0284215.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead 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...

Alvarez, L., Terrazas, A., Rojas, S. et al. 2023. Cortisol and pain-related behavior in hot-iron disbudded goat kids sedated with xylazine and locally infiltrated with lidocaine. Journal of Veterinary Behavior 63, 42–47.

Disbudding induces intense pain-related behavioral and physiological responses in goat kids. Using only regional anesthesia may not be effective in ameliorating these responses. We determined the effect of xylazine-sedation with or without regional infiltration of...

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...

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...

Archibald, W., Glynn, C. 2021. Refining cages for social housing of non-human primates on ADME studies. Animal Technology and Welfare 20(2), 172-174.

The assessment and understanding of Absorption, Distribution, Metabolism and Elimination (ADME) for new pharmaceuticals is required in regulatory submissions. Typically, ADME studies are conducted using metabolism cages designed for the single housing of animals to...

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...

Hausmann, J. C., Krisp, A. R., Mans, C. et al. 2021. Analgesic efficacy of tramadol and morphine in White's tree frogs (Litoria caerulea). JAALAS 60(6), 681-686.

Published data are sparse regarding the recognition of clinically relevant pain and appropriate analgesia in amphibians. The amphibian analgesia literature has primarily focused on nociceptive pathways in a single species, the northern leopard frog (Rana...

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...

Guerrero-Martin, S. M., Rubin, L. H., McGee, K. M. et al. 2021. Psychosocial stress alters the immune response and results in higher viral load during acute simian immunodeficiency virus infection in a pigtailed macaque model of human immunodeficiency virus. The Journal of Infectious Diseases 224(12), 2113–2121.

Although social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease...

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...

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...

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)...

Goodroe, A., Fitz, C., Bakker, J. 2020. Current topics in marmoset anesthesia and analgesia. ILAR Journal 61(2-3), 218-229.

Anesthetic and analgesics are essential components of both clinical and research procedures completed in marmosets. A review of current anesthetic and analgesic regimens for marmosets has been complied to provide a concise reference for veterinarians...

Engel, R. M., Thomas III, M. L., Banks, R. E. 2019. Regional anesthesia for dentistry and orofacial surgery in rhesus macaques (Macaca mulatta). JAALAS 58(2), 223-230.

Regional anesthesia is a commonly used adjunct to orofacial dental and surgical procedures in companion animals and humans. However, appropriate techniques for anesthetizing branches of the mandibular and maxillary nerves have not been described for...