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...

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...

Digranes, N., Haga, H. A., Nordgreen, J. 2023. High and hyper: Fentanyl induces psychomotor side-effects in healthy pigs. Animals 13(10), 1671.

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin...

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...

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...

Costa, G. L., Spadola, F., Di Pietro, S. et al. 2023. Tramadol vs. Lidocaine administered intraperitoneally and in incisional lines for the intraoperative and postoperative pain management of romifidine-telazol-anesthetized swine undergoing umbilical hernia repair. Animals 13(18), 2905.

The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred swine. The...

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...

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...

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...

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...

Torcivia, C., McDonnell, S. 2022. Efficacy of lidocaine topical solution in reducing discomfort reaction of horses to intramuscular vaccination. Animals 12(13), 1659.

Vaccinations via intramuscular injection are a key component of preventative health care in horses. Development of problematic behavioral aversion to injections is quite common. Our clinical impression has been that topical anesthetic applied to injection...

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...

Davies, J. R., Purawijaya, D. A., Bartlett, J. M. et al. 2022. Impact of refinements to handling and restraint methods in mice. Animals 12(17), 2173.

There is increasing evidence that, compared to non-aversive handling methods (i.e., tunnel and cupping), tail handling has a negative impact on mouse welfare. Despite this evidence, there are still research organisations that continue to use...

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...

Bethell, E. J., Khan, W., Hussain, A. 2022. A deep transfer learning model for head pose estimation in rhesus macaques during cognitive tasks: Towards a nonrestraint noninvasive 3Rs approach. Applied Animal Behaviour Science 255, 105708.

Head orientation is a measure of attention used in behavioral psychological research with non-human primates. It is used across a broad range of disciplines and settings, from the field to the laboratory. Field methods are...

O'Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

Chan, G., Si, C., Nichols, M. R. et al. 2022. Assessment of the safety and efficacy of pre-emptive use of extended-release buprenorphine for mouse laparotomy. JAALAS 61(4), 381-387.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR...

Barkus, C., Bergmann, C., Branco, T. et al. 2022. Refinements to rodent head fixation and fluid/food control for neuroscience. Journal of Neuroscience Methods 381, 109705.

The use of head fixation in mice is increasingly common in research, its use having initially been restricted to the field of sensory neuroscience. Head restraint has often been combined with fluid control, rather than...