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. 
McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

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...

Clarkson, J. M., Martin, J. E., McKeegan, D. E. F. 2022. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 56(5), 419-436.

Rodents are the most widely used species for scientific purposes. A critical pre-requisite of their use, based on utilitarian ethical reasoning, is the provision of a humane death when necessary for scientific or welfare grounds...

Ferreira, J. M., Félix, L., Jorge, S. et al. 2022. Anesthesia overdose versus rapid cooling for euthanasia of adult zebrafish. Zebrafish 19(4), 148-159.

The rapid increase in zebrafish use needs to be accompanied by research into the refinement of procedures. The European (EU) Directive lists three possible euthanasia methods for fish: anesthetic overdose, electrical stunning, and concussion. However...

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...

Hepps Keeney, C., Harrison, T. M. 2022. Euthanasia complications in non-domestic species. Journal of Zoological and Botanical Gardens 3(4), 616–623.

There are very few studies describing euthanasia complications in non-domestic species. The goal of this study was to survey veterinarians to determine what complications may commonly occur during the euthanasia of non-domestic species. An online...

Hickman, D. L. 2021. Wellbeing of mice euthanized with carbon dioxide in their home cage as compared with an induction chamber. JAALAS 60(1), 72-76.

The AVMA Guidelines on Euthanasia state that, to decrease potential distress of animals, the home cage should be used for the euthanasia of mice. The current study evaluated this recommendation by comparing behavioral and physiologic...

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...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

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...

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...

Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...

Bennett, T. E., Pavek, T. J., Schwark, W. S. et al. 2021. Comparison of nociceptive effects of buprenorphine, firocoxib, and meloxicam in a plantar incision model in Sprague–Dawley rats. JAALAS 60(5), 539-548.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

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...

Alemán-Laporte, J., Bandini, L. A., Garcia-Gomes, M. S. et al. 2020. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization. Laboratory Animals 54(2), 171–182.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory...

Składanowska-Baryza, J., Ludwiczak, A., Pruszyńska-Oszmałek, E. et al. 2020. Effect of two different stunning methods on the quality traits of rabbit meat. Animals 10(4), 700.

The aim of the study was to assess the effect of two different stunning methods on the level of blood stress indicators (cortisol, insulin, glucose) and rabbit meat quality. The experiment was conducted on crossbreds...

Frost, K., Shah, M., Leung , V. S. Y. et al. 2020. Aversion to desflurane and isoflurane in Sprague-Dawley rats (Rattus norvegicus). Animals 10(6), 950.

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

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...

Améndola, L., Weary, D. M. 2020. Understanding rat emotional responses to CO2. Translational Psychiatry 10, 253.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

Zude, B. P., Jampachaisri, K., Pacharinsak, C. 2020. Use of flavored tablets of gabapentin and carprofen to attenuate postoperative hypersensitivity in an incisional pain model in rats (Rattus norvegicus). JAALAS 59(2), 163–169.

Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin...