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. 
Fitzwater, A., Zhang, L. 2024. A cost-effective restraint method for safer subcutaneous scruff injections and reducing stress in mice and handlers. Laboratory Animal Science Professional 12(1) (January/February), 52-53.

Subcutaneous injection is a vital technique in mouse-based biomedical research. Compared to other injections, the subcutaneous method poses fewer technical challenges and reduces acute toxicity risks due to slower absorption. Several suitable subcutaneous injection sites...

Jessica, C.-G., Buendía-González, L., Ruiz-Gómez, M. L. et al. 2024. A minimally invasive procedure for blood extraction from Xenopus laevis allows follow up studies without euthanasia. Journal of Applied Animal Welfare Science 27(1), 192–199.

Blood extraction is extremely important for the development of scientific research; however, the existing methods for amphibian´s blood sampling are invasive, mainly leading to the euthanasia of the animal. Therefore, less intrusive methods that allow...

Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

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...

Swan, J., Boyer, S., Westlund, K. et al. 2023. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Frontiers in Behavioral Neuroscience 17, 1109886.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are...

Wolter, A., Bucher, C. H., Kurmies, S. et al. 2023. A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models. Scientific Reports 13(1), 3824.

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are...

Deng, J., Zhang, H., Wang, Q. et al. 2023. An optimized environmental DNA method to improve detectability of the endangered Sichuan taimen (Hucho bleekeri). Fishes 8(7), 339.

Environmental DNA (eDNA) techniques have emerged as a cost-effective and non-invasive strategy for monitoring the distribution of endangered aquatic species. Despite their numerous advantages, operational uncertainty at each step of the process represents a significant...

Xu, J. J., Lucero, M. Y., Herndon, N. L. et al. 2023. Comparison of a minimally invasive transthoracic approach and a surgical method for intrapleural injection of tumor cells in mice. Comparative Medicine 73(2), 120–126.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing...

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...

Esparza, K. 2023, August. Moving away from soiled bedding sentinels—The (R)evolution in rodent health screening. Animal Technology and Welfare 22(2), 158–160.

Traditional health monitoring methods consisted of Soiled Bedding Sentinels (SBS (i.e. animals exposed to dirty bedding from colony animals)), which require the euthanasia of SBS. Numerous studies have demonstrated that SBS may not accurately represent...

Marin, N., Moragon, A., Gil, D. et al. 2023. Acclimation and blood sampling: Effects on stress markers in C57Bl/6J mice. Animals 13(18), 2816.

Blood sampling in rodents is common practice in scientific studies. Some of the refined methods widely used are the puncture of the saphenous vein or tail vein, or even tail docking. The handling needs of...

Anderson, B. J., Curtis, A. M., Jen, A. et al. 2023. Plasma metabolomics supports non-fasted sampling for metabolic profiling across a spectrum of glucose tolerance in the Nile rat model for type 2 diabetes. Lab Animal 52(11), 269–277.

Type 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic...

Bertani, S., Donadi, A., Franchi, J. et al. 2023. Blood microsampling in cynomolgus monkey and evaluation of plasma PK parameters in comparison to conventional sampling. Journal of Pharmacological and Toxicological Methods 123, 107298.

Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive...

Brake, M. E., Russ, B. P., Gansebom, S. et al. 2023. Effects of extended-release buprenorphine on mouse models of influenza. Comparative Medicine 73(6), 466–473.

Mice are widely used as small animal models for influenza infection and immunization studies because of their susceptibility to many strains of influenza, obvious clinical signs of infection, and ease of handling. Analgesia is rarely...

Buhr, P., Kolstrup, S., Nikolajsen, L.-L. et al. 2023. The anaesthetic effects of ketamine/xylazine/midazolam in C57Bl/6JRj mice. Scandinavian Journal of Laboratory Animal Science 49, 21–27.

We wished to improve the efficacy and safety of ketamine/xylazine anaesthesia in C57Bl/6JRj mice and achieve a surgical anaesthesia lasting 20-30 minutes, aiming at fewer anaesthesia related deaths and using the subcutaneous injection route to...

George, A. J., O’Malley, C. I., Bulock, R. E. et al. 2023. Implementation of an alternative training method for cardiac blood collection in mice. JAALAS 62(6), 487–493.

Training personnel to work with animals presents a variety of challenges, both logistically and with regard to animal welfare. These issues make training an ideal opportunity to evaluate practices and to implement the 3R principles...

Lopez-Echeverria, G., Alamaw, E., Gorman, G. et al. 2023. Comparing three formulations of buprenorphine in an incisional pain model in mice. JAALAS 62(6), 531–537.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based...

McKenna, B. A., Weaver, H. L., Kim, J. et al. 2023. A pharmacokinetic and analgesic efficacy study of carprofen in female CD1 mice. JAALAS 62(6), 545–552.

The minimization of pain in research animals is a scientific and ethical necessity. Carprofen is commonly used for pain management in mice; however, some data suggest that the standard dosage of 5 mg/kg may not...

Chen, D. D., Molk, D. M., Palley, L. S. et al. 2023. Pinna edge biopsy of 7 and 21 day old C57BL/6 mice as a method for identification and genotyping. JAALAS 62(5), 438–448.

Identifying and genotyping mice prior to weaning can be useful for mouse colony management. Mice of an undesired genotype can be identified prior to weaning and removed from further study, resulting in a reduction of...

George, A. J., Harmsen, B. J., Ford, J. A. et al. 2023. Evaluation of submental blood collection in mice (Mus musculus). JAALAS 62(1), 92–98.

The submental route is an option for nonterminal and serial blood collection in mice. This study compared the submental route to the maxillary route (also referred to as the submandibular route). The study used male...

Illario, J. A., Osborn, K. G., Garcia, A. V. et al. 2023. Comparative pharmacokinetics and injection site histopathology in nude mice treated with long-acting buprenorphine formulations. JAALAS 62(2), 147–152.

Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of...

Kim, J., Cannon, B. A., Freeman, L. E. et al. 2023. High-dose meloxicam provides improved analgesia in female CD1 mice: A pharmacokinetic and efficacy study. JAALAS 62(1), 74–80.

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses...

Riddell, D. L., Hyndman, T. H., Bowden, R. S. et al. 2023. Use of a low-calorie flavored gel to facilitate oral self-administration of analgesics in mice. JAALAS 62(2), 163–169.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to...

Yang, P., Hish, G., Lester, P. A. 2023. Comparison of systemic extended-release buprenorphine and local extended-release bupivacaine-meloxicam as analgesics for laparotomy in mice. JAALAS 62(5), 416–422.

Extended-release (ER) local anesthetics can be used in multi-modal analgesia or in situations in which systemic analgesics may alter animal physiology and thus introduce interpretational confounds. In this study, we compared the analgesic efficacy of...

Mainau, E., Llonch, P., Temple, D. et al. 2022. Alteration in activity patterns of cows as a result of pain due to health conditions. Animals 12(2), 176.

The main conditions and diseases considered painful in dairy cows are mastitis, lameness, calving (including dystocia and caesarean section) and metritis. The cattle literature reports that deviation from normal daily activity patterns (both increased and/or...