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. 
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...

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...

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...

Doss, G. A., Mans, C. 2020. Antinociceptive efficacy and safety of subcutaneous buprenorphine hydrochloride administration in African pygmy hedgehogs (Atelerix albiventris). Journal of the American Veterinary Medical Association 257(6), 618-623.

OBJECTIVE: To evaluate antinociceptive efficacy and safety of SC buprenorphine hydrochloride administration in African pygmy hedgehogs (Atelerix albiventris). ANIMALS: 12 healthy adult hedgehogs (7 males and 5 females). PROCEDURES: 3 crossover experimental trials were performed...

Andrews, D. D., Fajt, V. R., Baker, K. C. et al. 2020. A comparison of buprenorphine, sustained release buprenorphine, and high concentration buprenorphine in male New Zealand white rabbits. JAALAS 59(5), 546-556.

Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could...

Stewart, L. A., Imai, D. M., Beckett, L. et al. 2020. Injection-site reactions to sustained-release meloxicam in Sprague–Dawley rats. JAALAS 59(6), 726-731.

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable...

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...

Raillard, M., Detotto, C., Grepper, S. et al. 2019. Anaesthetic and perioperative management of 14 male New Zealand white rabbits for calvarial bone surgery. Animals 9(11), 896.

Calvarial bone surgery on rabbits is frequently performed. This report aims to document a simple and practical anaesthetic and perioperative management for this procedure. Fourteen male New Zealand white rabbits were included in the study...

Baker, S. W., Tucci, E. R., Felt, S. A. et al. 2019. A bird's-eye view of regulatory, animal care, and training considerations regarding avian flight research. Comparative Medicine 69(3), 169–178.

A thorough understanding of how animals fly is a central goal of many scientific disciplines. Birds are a commonly used model organism for flight research. The success of this model requires studying healthy and naturally...

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...

Klune, C. B., Larkin, A. E., Leung, V. S. Y. et al. 2019. Comparing the Rat Grimace Scale and a composite behaviour score in rats. PLOS ONE 14(5), e0209467.

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression...

Colby, L. A., Nowland, M. H., Kennedy, L. H. 2019. Clinical Laboratory Animal Medicine: An Introduction (5th ed). Wiley-Blackwell, Ames, IA.

The revised fifth edition of Clinical Laboratory Animal Medicine: An Introduction is an accessible guide to basic information for conducting animal research safely and responsibly. It includes a review of the unique anatomic and physiologic...

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...

Fox, L., Mans, C. 2018. Analgesic efficacy and safety of buprenorphine in chinchillas (Chinchilla lanigera). JAALAS 57(3), 286-290.

Buprenorphine is routinely used in chinchillas at reported doses of 0.01 to 0.1 mg/kg IM or SC. However, these dose recommendations are based on anecdotal reports or extrapolation from studies in other species. Therefore, the...

Evenson, E. A., Mans, C. 2018. Analgesic efficacy and safety of hydromorphone in chinchillas (Chinchilla lanigera). JAALAS 57(3), 282-285.

Limited information is available regarding the efficacy of opioid analgesics in chinchillas. Here we sought to evaluate the analgesic efficacy and safety of hydromorphone in chinchillas. In a randomized, controlled, blind, complete crossover design, hydromorphone...

Smith, B. D., Vail, K. J., Carroll, G. L. et al. 2018. Comparison of etomidate, benzocaine, and MS222 anesthesia with and without subsequent flunixin meglumine analgesia in African clawed frogs (Xenopus laevis). JAALAS 57(2), 202-209.

Often few alternative anesthetics for exotic species are available, due to the small numbers of these animals used in research. In this study, we evaluated the depth and duration of anesthesia in Xenopus laevis after...

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...

Nunamaker, E. A., Goldman, J. L., Adams, C. R. et al. 2018. Evaluation of analgesic efficacy of meloxicam and 2 formulations of buprenorphine after laparotomy in female Sprague-Dawley rats. JAALAS 57(5), 498–507.

Managing postoperative pain in rodents is an important part of any animal care and use program, and identifying an optimal analgesic plan for a surgical procedure is critical to providing for animal welfare. Opioids and...

Hestehave, S., Munro, G., Christensen, R. et al. 2017. Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes? PLOS ONE 12(11), e0188113.

Introduction: The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment...

Thomas, A. A., Detilleux, J., Sandersen, C. F. et al. 2017. Minimally invasive technique for intrathecal administration of morphine in rats: Practicality and antinociceptive properties. Laboratory Animals 51(5), 479-489.

The intrathecal (IT) route of administration represents a means to reduce the dose of morphine administered for analgesia, potentially minimizing interactions between opioid effects and experimental outcomes. Perceived technical difficulty, and previously described invasive methods...

Hestehave, S., Munro, G., Brønnum Pedersen, T. et al. 2017. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats. Laboratory Animals 51(3), 264-272.

Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in...