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. 
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...

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...

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...

Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Kendall, L. V., Singh, B., Bailey, A. L. et al. 2021. Pharmacokinetics and efficacy of a long-lasting, highly concentrated buprenorphine solution in mice. JAALAS 60(1), 64-71.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate...

Furumoto, K., Ogita, K., Kamisaka, T. et al. 2021. Effects of multimodal analgesic protocol, with buprenorphine and meloxicam, on mice well-being: A dose finding study. Animals 11(12), 3420.

The anesthetic or analgesic agent of choice, route and frequency of anesthetic or analgesic administration, and stressors induce distress during the perioperative period. We evaluated a multimodal analgesic protocol using buprenorphine and meloxicam on the...

Foley, P. L., Kendall, L. V., Turner, P. V. 2019. Clinical management of pain in rodents. Comparative Medicine 69(6), 468–489.

The use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. Factors contributing to this gap...

Smith J. C. 2019. A review of strain and sex differences in response to pain and analgesia in mice. Comparative Medicine 69(6), 490–500.

Pain and its alleviation are currently a highly studied issue in human health. Research on pain and response to analgesia has evolved to include the effects of genetics, heritability, and sex as important components in...

Cho, C., Michalidis, V., Lecker, I. et al. 2019. Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale. Scientific Reports 9, 359.

Most research laboratories abide by guidelines and mandates set by their research institution regarding the administration of analgesics to control pain during the postoperative period. Unfortunately, measuring pain originating from the head is difficult, making...

Bauer, C., Schillinger, U., Brandl, J. et al. 2019. Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice. Laboratory Animals 53(5), 459–469.

In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to...

Redaelli, V., Papa, S., Marsella, G. et al. 2019. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury. PLOS ONE 14(10), e0224337.

The principles of Refinement, Replacement and Reduction (3R’s) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord...

Miller, K. A., Hill, N. J., Carrasco, S. E. et al. 2019. Pharmacokinetics and safety of intramuscular meloxicam in zebra finches (Taeniopygia guttata). JAALAS 58(5), 589–593.

Meloxicam is the most frequently used NSAID in birds; however, its elimination t1/2 is highly variable among species. Because zebra finches that require analgesia could benefit from receiving meloxicam, we performed a pharmacokinetic study involving...

Lofgren, J., Miller, A. L., Shan Lee, C. C. et al. 2018. Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models. Laboratory Animals 52(4), 351-364.

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10...

Evangelista-Vaz, R., Bergadano, A., Arras, M. et al. 2018. Analgesic efficacy of subcutaneous–oral dosage of tramadol after surgery in C57BL/6J mice. JAALAS 57(4), 368-375.

This study investigated the analgesic activity of tramadol in female C57BL/6J mice by using a single subcutaneous injection (25 mg/kg) of tramadol combined with the same dose given in drinking water for 24 h. We...

Beninson, J. A., Lofgren, J. L., Lester, P. A. et al. 2018. Analgesic efficacy and hematologic effects of robenacoxib in mice. JAALAS 57(3), 258-267.

NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease...

Jirkof, P., Arras, M., Cesarovic, N. 2018. Tramadol:Paracetamol in drinking water for treatment of post-surgical pain in laboratory mice. Applied Animal Behaviour Science 198, 95-100.

In the search for stress-free analgesia administration for laboratory mice suffering pain, oral delivery of Tramadol:Paracetamol (T:P) shows great promise. Here, we monitored the analgesic efficacy and side effects of a T:P combination administered solely...

Jirkof, P. 2017. Side effects of pain and analgesia in animal experimentation. Lab Animal 46(4), 123-128.

This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility...

Ferguson, R. 3Rs improvements in the Bexsero® (Meningitis B) vaccine. Animal Technology and Welfare 16(2), 150-152.

Bexsero® is a new vaccine in the UK which since September 2015 has been added to the childhood immunisation programme for the prevention of Meningitis B. The in-vivo test as performed in Biological Services Division...

Jeger, V., Hauffe, T., Nicholls-Vuille, F. et al. 2016. Analgesia in clinically relevant rodent models of sepsis. Laboratory Animals 50(6), 418-426.

Postoperative analgesia in rodent sepsis models has been considerably neglected in the past. However, intentions to model clinical practice, increasing awareness of animal ethics, efforts to apply the 3Rs (replacement, reduction, refinement), and stricter legislation...