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...

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...

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...

Klabukov, I., Shestakova, V., Krasilnikova, O. et al. 2023. Refinement of animal experiments: Replacing traumatic methods of laboratory animal marking with non-invasive alternatives. Animals 13(22), 3452.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than...

Nyqvist, D., Schiavon, A., Candiotto, A. et al. 2023. PIT-tagging Italian spined loach (Cobitis bilineata): Methodology, survival and behavioural effects. Journal of Fish Biology 102(3), 575–580.

The Italian spined loach (Cobitis bilineata) is an elongated, small-sized (

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...

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...

Griffioen, A. B., Janssen, W., Menke,T. et al. 2022. Does tagging transparent fish increase predation risk? A laboratory study with glass eel (Anguilla anguilla) and sea bass (Dicentrarchus labrax). Journal of Fish Biology 100(1), 184-191.

Barriers in the estuaries of the rivers prevent the immigration of glass eels (Anguilla anguilla) arriving on the European coast every spring. This leads to an unnatural accumulation of migrating glass eels below the barriers...

Swarr, T. R., Myrick, C. A., Fitzpatrick, R. M. 2022. Tag retention in and effects of passive integrated transponder tagging on survival and swimming performance of a small-bodied darter. Journal of Fish Biology 100(3), 705-714.

Fisheries biologists have been hesitant to use passive integrated transponder (PIT) tags in small-bodied fishes (40–200 mm TL) such as darters (Percidae: Etheostomatinae) because of the fishes' size and potential effect on swimming performance. The authors used...

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...

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...

Runde, B. J., Buckel, J. A., Bacheler, N. M. et al. 2022. Evaluation of six methods for external attachment of electronic tags to fish: Assessment of tag retention, growth and fish welfare. Journal of Fish Biology 101(3), 419-430.

External attachment of electronic tags has been increasingly used in fish studies. Many researchers have used ad hoc attachment methods and provided little or no validation for the assumption that tagging itself does not bias...

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...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Reifenrath, J., Heider, M., Kempfert, M. et al. 2022. Buprenorphine in rats: Potent analgesic or trigger for fatal side effects? Acta Veterinaria Scandinavica 64(1), 37.

With ongoing animal welfare efforts, multimodal analgesia is often recommended to implement in study protocols. Buprenorphine with very potent analgesic effect is a standard opioid for the use in this context in rats. In this...

Bekkozhayeva, D., Cisar, P. 2022. Image-based automatic individual identification of fish without obvious patterns on the body (scale pattern). Applied Sciences 12(11), 5401.

The precision fish farming concept has been widely investigated in research and is highly desirable in aquaculture as it creates opportunities for precisely controlling and monitoring fish cultivation processes and increasing fish welfare. The automatic...

Huss, M. K., Pacharinsak, C. 2022. A review of long-acting parenteral analgesics for mice and rats. JAALAS 61(6), 595–602.

Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data...

Blaney, A., Jampachaisri, K., Huss, M. K. et al. 2021. Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLOS ONE 16(2), e0246213.

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in...

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...

Katz, E. M., Huss, M. K., Jampachaisri, K. et al. 2021. Buprenorphine, but not lidocaine, effectively attenuates post-operative thermal hypersensitivity in an incisional model in neonatal rats (Rattus norvegicus). Scandinavian Journal of Laboratory Animal Science 47(1), 1-11.

There is limited information on safe and effective neonatal rodent analgesia. The aim of this study was to evaluate the efficacy and duration of analgesia provided by buprenorphine (Bup) and lidocaine (Lid) in an incisional...

Thomsen, P. T., Hansen, J. H., Herskin, M. S. 2021. Dairy calves show behavioural responses to hot iron disbudding after local anaesthesia with procaine. Veterinary Record 188(4), 270-276.

Background: The efficacy of procaine as anaesthetic for disbudding of calves is largely unknown. Likewise, information about effect of interval from local anaesthesia to disbudding and the size of the hot iron used is missing...

Sheil, M., Chambers, M., Polkinghorne, A. et al. 2021. Topical application of lidocaine and bupivacaine to disbudding wounds in dairy calves: Safety, toxicology and wound healing. Animals 11(3), 869.

Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bupivacaine, adrenaline and cetrimide. Applied to wounds, it is reported to reduce the pain experienced by calves following thermocautery disbudding. While lidocaine and bupivacaine...

Rácz, A., Allan, B., Dwyer, T. et al. 2021. Identification of individual zebrafish (Danio rerio): A refined protocol for VIE tagging whilst considering animal welfare and the principles of the 3Rs. Animals 11(3), 616.

In aquatic ecology, studies have commonly employed a tagging technique known as visible implant elastomer (VIE). This method has not been widely adopted by the zebrafish research community and also lacks refinement with regard to...