13840110d2d515487e83b87 disadvantages of using rats in research
J. Pharmacol. Joint Bone Spine 72, 359371. | Terms | Privacy Policy, Rodent Hypoxia-Ischemia Models for Cerebral Palsy Research: A Systematic Review, The influence of immaturity on hypoxic-ischemic brain damage in the rat. doi: 10.1016/s0165-0270(01)00483-6, Millecamps, M., Jourdan, D., Leger, S., Etienne, M., Eschalier, A., and Ardid, D. (2005). Vet. The response temperature is dependent on the starting temperature, ambient temperature and rate of heating, with faster heat ramps resulting in higher response temperatures (Tjolsen et al., 1991; Yalcin et al., 2009). You want to survey as large a sample size as possible; smaller sample sizes get decreasingly representative of the entire population. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. J. Neurosci. Unilateral hot plate test: a simple and sensitive method for detecting central and peripheral hyperalgesia in mice. Although animal models of pain have undoubtedly provided key advances, the advantages and disadvantages of each model and behavioral test should be taken into account to obtain objective and meaningful results that will improve our understanding and management of pain. Phone: +1 (631) 468-8530 52, 34703478. Facial expression is subjectively scored for severity of pain based on five facial features (ear position, eye closing, cheek bulging, whisker position, and nose bulging). Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. By comparing the frequencies of behaviors in animal models of pain as opposed to control states, inference about different pain states (and especially spontaneous nociception) can be made. A disadvantage of this method is that the number of measurements per animal is variable and that it requires repeated, time-intensive measurements, which may lead to sensitization or learnt responses. 2023 Leaf Group Ltd. / Leaf Group Media, All Rights Reserved. A., Possani, L. D., Cabot, P. J., Lewis, R. J., et al. In mice, ES cells can be maintained in their pluripotent state easily. Three main ethical attitudes towards animals are reviewed here. The framework for these standards and guidelines are based on the principles of the 3Rs (replacement, reduction, refinement). Boehmerle, W., Huehnchen, P., Peruzzaro, S., Balkaya, M., and Endres, M. (2014). However mice are less likely to survive the hypoxia-ischemia procedure, display a wider variety of brain damage, and have dramatic strain-to-strain differences. (2005). Lancet 383(9924): 1240-9. Other advantages of this methodology include eliminating the phenomenon of clustered selection and a low . J. Pharmacol. Second, the number of flinches over a set period of time can be recorded at a specific temperature (Deuis et al., 2013; Zimmermann et al., 2013). It should be noted that behavioral assessment of animals in groups (even if blinded) is typically not sufficient, with a preferred method being measurements performed on animals in random order by an investigator blinded to the treatment group each animal has been allocated to. Rodents are allowed to freely move between a reference plate (neutral temperature) and test plate. In this model, the lateral plantar skin of the hind paw, which is the area of innervation of the sural nerve, has the greatest reduction in mechanical thresholds compared to other innervation areas of the plantar skin (Decosterd and Woolf, 2000). The MouseMet or RatMet electronic Von Frey systems deliver a mechanical stimulus via a hand-held probe (Figure 1B). Characterization of the foot withdrawal response to noxious radiant heat in the rat. A radiant or infrared heat source is positioned underneath the animal and aimed at the plantar surface of the hind paw (Figure 3C). A radiant or infrared heat source is focused on the plantar surface of the hind paw and the time taken to withdraw from the heat stimulus is recorded. doi: 10.1016/0304-3959(92)90041-9, Knowlton, W. M., Bifolck-Fisher, A., Bautista, D. M., and McKemy, D. D. (2010). The experiment begins by testing the response to a filament estimated to be close to the 50% withdrawal threshold. Methods 255, 92103. 119, 481488. Assessment of thermal sensitivity in rats using the thermal place preference test: description and application in the study of oxaliplatin-induced acute thermal hypersensitivity and inflammatory pain models. Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice. The dynamic hot plate test, first described in 1984, uses an increasing temperature ramp rather than a constant temperature. Efficient analysis of experimental observations. J. doi: 10.1172/jci42843, Dubner, R. (1983). The second view, by Singer, considers animals as sentient creat Mice count morally because they can be harmed. Rodents are allowed to freely move along a liner or circular surface with a temperature gradient. 27, 1368013690. It also demonstrates two additional concepts, originally outlined by Pavlov. The laboratory rat, Rattus norvegicus, has been used in biomedical research for more than 150 years, and in many cases remains the model of choice for studies of physiology, behavior, and complex human disease. Coding of facial expressions of pain in the laboratory mouse. In addition, a programmable hold step with constant force application can also be incorporated in the experimental setup to determine the time to withdrawal (Lu and Schmidtko, 2013). Typically, the experimental setup consists of a test plate at a fixed temperature (usually between 5C and 55C) that is placed adjacent to a reference plate at neutral temperature (usually between 25C and 30C; Figure 5A). Although animal research may have ethical concerns, the US has regulated its practice since 1966. (C) Randall-Selitto test (handheld device). Cerebral palsy. The power of mouse models proved to be so clear however that the same abilities in rat continued to be desired and pursued. It is the premier source of information on the laboratory rat. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. Osteoarthr. A burrow is placed in the cage of a rodent filled with a suitable substrate (such as food pellets, sand, or marbles). Neuron 54, 379386. J. Pharmacol. PLoS One 10:e0125822. Response latencies in the tail-flick test depend on tail skin temperature. Received: 04 April 2017; Accepted: 22 August 2017; Published: 06 September 2017. While this is generally not an issue when testing the anti-nociceptive effects of compounds delivered systematically or when phenotyping transgenic mice, this may confound the results for unilateral models of pain or for compounds administered by intraplantar injection. Hyperalgesia and allodynia: peripheral mechanisms. The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. The cold plate test is one of the simplest assays to determine behavioral responses to both noxious and innocuous cold temperatures in both mice and rats. doi: 10.1097/NNR.0000000000000082, Gritsch, S., Bali, K. K., Kuner, R., and Vardeh, D. (2016). While the plantar surface of the hind paw is the most commonly used area for testing, other areas of the body, including the dorsal surface of the hind paw or the abdomen can also be used (Minett et al., 2014). Significant determinants of mouse pain behaviour. Digigait quantitation of gait dynamics in rat rheumatoid arthritis model. Rodents are placed individually in small enclosures with a glass floor. Rev. Woolfe, G., and Macdonald, A. D. (1944). The CatWalk method: assessment of mechanical allodynia in experimental chronic pain. For example, in the spared nerve injury model, the tibial and common peroneal nerves are axotomized, leaving only the sural nerve intact. doi: 10.1093/neuonc/nou048, Deuis, J. R., and Vetter, I. The manual Von Frey test, developed by the physiologist Maximilian von Frey, is a method of evaluating mechanical allodynia in mice and rats. doi: 10.1016/j.jneumeth.2015.08.010, Brenner, D. S., Golden, J. P., and Gereau, R. W. IV (2012). Behav. Assoc. The up-down Von Frey method is used to determine the mechanical force required to elicit a paw withdrawal response in 50% of animals, based on the statistical formula used to determine LD50s (Dixon, 1980; Chaplan et al., 1994). Neurosci. Methods 141, 261269. It has since been applied to a variety of species, to leverage similarities between the brains of humans and different animals. doi: 10.1038/nrn2606, Moqrich, A., Hwang, S. W., Earley, T. J., Petrus, M. J., Murray, A. N., Spencer, K. S., et al. Eur. J. Neurosci. Gait analysis in freely walking rodents is used to study changes in limb movement and positioning in models with sensori-motor dysfunction, including Parkinsons disease, spinal cord injury and stroke. Burns 43, 304309. Quantification of more subtle behaviors, such as walking backwards or grooming of the front paws has thus been proposed as alternatives to quantify cold pain behaviors, although the validity of this approach has not been systematically assessed. doi: 10.1371/journal.pone.0104458, Minett, M. S., Quick, K., and Wood, J. N. (2011). However, replacement or substitution of animals for nonsentient materials is difficult in pain research due to the nature of the behavioral experiments. First, the response to a specific temperature (typically 5C to 15C) can be recorded (Allchorne et al., 2005). The test begins by assessing the response to a filament of the lowest force (in this case 0.4 grams-force) for a set number of applications (in this case five times). Attenuated cold sensitivity in TRPM8 null mice. Behavioural research shows rats are more suited to studies on learning and cognition because they are more capable of learning tasks than other species. The Hargreaves test, first described in 1988, is a method used to quantify heat thresholds in the hind paws of mice and rats upon application of a radiant or infrared heat stimulus (Hargreaves et al., 1988). doi: 10.1002/9780470942390.mo110116, Mogil, J. S. (2009). (2011). (B) Continuous temperature gradient assay. Researchers choose rats over other species for a number of reasons: Pain 150, 340350. 1, 118121. This includes minimizing the duration of models, replacing nocifensive model compounds for ones that cause shorter lasting nociception, or reducing the administered doses of compounds. A disadvantage of systems that only use video recordings (e.g., DigiGait, GaitScan/TreadScan) is that they cannot measure paw print intensity or pressure (weight bearing parameters), which is relevant for pain models. (2010). This therefore provides measure of paw withdrawal threshold on a continual scale, as the force is applied continuously and not in steps. 150, 165171. The Mouse Grimace Scale is highly accurate, but generally requires significant amounts of nociception in order to elicit a visible response, which limits its use. The Rat Grimace Scale is also scored 02 depending on observed changes in facial features, and evaluates the extent of orbital tightening, nose/cheek flattening, ear change and whisker change (Sotocinal et al., 2011). (1988). Significant progress was made in 2008 by Professor Austin Smiths lab at Cambridge, and Professor Qi-Long Yings lab at the University of Southern California with the first targeting of rat ES cells achieved. Toxicol. Neurosci. Exp. From a physiological standpoint, more is known about the responses and pathways in rats than in other species due to the wealth of data collected over the years. Exp. The RatMet or MouseMet von Frey filament (0.3 and 0.5 mm tip diameter, delivering forces of 180 g and 0.17 g, respectively) is placed against the plantar surface of the paw and the force is linearly increased via rotation of the device handle (Deuis and Vetter, 2016). Pain 88, 5360. Functional characterization of a mouse model for central post-stroke pain. The rat dies of other causes before tests can show the neurological damage that can be caused by long-term, low-dose exposure to gasoline. (2000). engagement in scientific research and . opportunities for species-specific behaviour), handling, procedures at daytime in nocturnal species, changes in groups for randomization, and too many male animals caged together. However, it is unclear to what degree changes in gait in rodent models reflect altered pain or nociception, or conversely, anti-nociception or analgesia. Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target. Meloxicam prevents COX-2-mediated post-surgical inflammation but not pain following laparotomy in mice. The force at which this response occurs is recorded automatically by the apparatus and is designated as the paw withdrawal threshold. Similarly, measures to improve data quality, including appropriate randomization and blinding procedures, are key to ensure validity of the obtained results. Research scientists worldwide agree that the use of rat models for disease research and experimentation has become more relevant in the past few years. Methods used to assess mechanically evoked pain like behaviors in rodents. Accordingly, dynamic weight bearing or gait analysis may provide similar data without the need for extensive animal and experimenter training. 2 The human, social, and economic burden of burns is considerable with an estimated annual expenditure of >$2 billion . These neurons are pseudo-unipolar, with a peripheral branch that terminates in the skin or viscera and a central branch that terminates in the spinal cord. They know how to use their own litter tray at home. Lett. 32, 5260. (2006). For people who choose to own rats at home, here are some of the benefits that they can receive: Rats are very intelligent animals. General adaptation syndrome was discovered accidentally by Selye whilst he was conducting experiments on rats at McGill University in Montreal, Canada.
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