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. 
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...

Maidanskaia, E. G., Mirra, A., Marchionatti, E. et al. 2023. Antinociceptive, sedative and excitatory effects of intravenous butorphanol administed alone or in combination with detomidine in calves: A prospective, randomized, blinded cross-over study. Animals 13(12), 1943.

The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol...

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...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

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...

Serrano, C., Antonio, J. 2022. Ultrasound guided surgery as a refinement tool in oncology research. Animals 12(23), 3445.

Refinement is one of the ethical pillars of the use of animals in research. Ultrasonography is currently used in human medicine as a surgical tool for guided biopsies and this idea can be applied to...

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...

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...

Lomb, J., Mauger, A., von Keyserlingk, M. A. G. et al. 2021. Effects of positive reinforcement training for heifers on responses to a subcutaneous injection. Journal of Dairy Science 104(5), 6146-6158.

Cattle are subjected to routine procedures that require restraint and close contact to humans, which are both potentially aversive to the animal. Positive reinforcement training techniques may affect how animals perceive and respond to these...

Espinoza, C., Lomax, S., Windsor, P. 2020. The effect of topical anaesthesia on the cortisol responses of calves undergoing dehorning. Animals 10(2), 312.

Dehorning causes pain and distress to cattle, and there is a need to provide effective and practical analgesia to improve animal welfare. We conducted an experiment to determine the effect of a modified post-operative topical...

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...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

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...

Larson, C. M., Wilcox, G. L., Fairbanks, C. A. 2019. Defining and managing pain in stroke and traumatic brain injury research. Comparative Medicine 69(6), 510–519.

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other...

Rasys, A. M., Divers, S. J., Lauderdale, J. D. et al. 2020. A systematic study of injectable anesthetic agents in the brown anole lizard (Anolis sagrei). Laboratory Animals 54(3), 281–292.

Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration...

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...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

Clutton, R. E. 2020. An Anglocentric history of anaesthetics and analgesics in the refinement of animal experiments. Animals 10(10), 1933.

Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK)...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

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)...