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...

Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

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...

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...

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...

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...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

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...

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...

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...

Wendler, P., Ertl, N., Flügger, M. et al. 2020. Influencing factors on the foot health of captive Asian elephants (Elephas maximus) in European zoos. Zoo Biology 39(2), 109-120.

Pathological lesions of feet occur frequently in captive elephant populations. To improve foot health, it is important to identify risk factors associated with such pathologies. Several previous studies have analyzed potentially influencing factors but were...

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...

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)...

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...

Smith, A. A., Halliday, L. C., Lindeblad, M. O. et al. 2019. Evaluation of analgesic patches in cynomolgus macaques (Macaca fascicularis). JAALAS 58(3), 356-361.

Opioids are widely used in veterinary and human medicine to manage pain. However, there is a paucity of information in the literature regarding the pharmacokinetics of opioid transdermal patches (TDP) in NHP. Therefore, to determine...

Chatigny, F. 2019. The controversy on fish pain: A veterinarian’s perspective. Journal of Applied Animal Welfare Science 22(4), 400-410.

Fish welfare is still a relatively new field. As such, regulations and protocols to ensure fish welfare are currently limited and vary considerably in different jurisdictions. This is in part because of the ongoing controversy...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...

Ehrlich, O., Karamalakis, A., Krylov, A. J. et al. 2019. Clove oil and AQUI-S efficacy for zebrafish embryo, larva, and adult anesthesia. Zebrafish 16(5), 451-459.

Since the use of the zebrafish Danio rerio genetic model organism within the scientific research community continues to grow rapidly, continued procedural refinement to support high-quality, reproducible research and improve animal welfare remains an important...

Fox, L., Mans, C. 2018. Analgesic efficacy and safety of buprenorphine in chinchillas (Chinchilla lanigera). JAALAS 57(3), 286-290.

Buprenorphine is routinely used in chinchillas at reported doses of 0.01 to 0.1 mg/kg IM or SC. However, these dose recommendations are based on anecdotal reports or extrapolation from studies in other species. Therefore, the...

Evenson, E. A., Mans, C. 2018. Analgesic efficacy and safety of hydromorphone in chinchillas (Chinchilla lanigera). JAALAS 57(3), 282-285.

Limited information is available regarding the efficacy of opioid analgesics in chinchillas. Here we sought to evaluate the analgesic efficacy and safety of hydromorphone in chinchillas. In a randomized, controlled, blind, complete crossover design, hydromorphone...

Chatigny, F., Creighton, C. M., Stevens, E. D. 2018. Updated review of fish analgesia. JAALAS 57(1), 5-12.

Analgesics are an integral part of routine pain management in mammals, yet their use in fish is still limited. Some recommendations on the use of analgesics in fish are currently in the literature; however, information...

Webb, S. J. N., Hau, J., Schapiro, S. J. 2018. Refinements to captive chimpanzee (Pan troglodytes) care: a self-medication paradigm. Animal Welfare 27(4), 327-341.

In an effort to enhance welfare, behavioural management continually refines methods of non-human primate (NHP) care. Chimpanzees (Pan troglodytes) are one of the most cognitively complex captive NHPs and they have been observed to self-medicate...

Chance, R. J., Cameron, G. A., Fordyce, M. et al. 2018. Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar. Journal of Fish Biology 93(6), 1069-1081.

Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research...

Lopez-Luna, J., Al-Jubouri, Q., Al-Nuaimy, W. et al. 2017. Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish. Journal of Experimental Biology 220(8), 1451-1458.

Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a...

De Lombaert, M. C. M., Rick, E. L., Krugner-Higby, L. A. et al. 2017. Behavioral characteristics of adult zebrafish (Danio rerio) after MS222 anesthesia for fin excision. JAALAS 56(4), 377-381.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all Husbandry & Management procedures should be evaluated for their effects on mortality, behavior, and physiology...