Anim. Lab. Pain 14, 628637. doi: 10.1016/s0165-0270(01)00483-6, Millecamps, M., Jourdan, D., Leger, S., Etienne, M., Eschalier, A., and Ardid, D. (2005). Some examples of human disorders and diseases for which mice and rats are used as models include: Hypertension Diabetes Cataracts Obesity Seizures Respiratory problems Deafness Parkinson's. An advantage of this assay is that the endpoint is objective and requires minimal experience by the investigator to perform. Alternatively, a continuous temperature gradienteither in linear (Figure 5B) or circular formcan be used to determine the preferred temperature in freely moving animals (Moqrich et al., 2005; Touska et al., 2016). At least six responses around the estimated threshold are required for optimal calculation of the 50% threshold (Dixon, 1980). doi: 10.1016/s0885-3924(05)80022-3, Giglio, C. A., Defino, H. L., da-Silva, C. A., de-Souza, A. S., and Del Bel, E. A. doi: 10.1016/j.pain.2006.01.041, Roughan, J. V., Bertrand, H. G., and Isles, H. M. (2016). While the underlying principle of the temperature gradient assay is similar to the two-temperature choice assay, the animal is free to explore along the gradient (usually between 4C and 65C over a length of 120 cm) until they settle within their preferred temperature or comfort zone. Thus, the hot plate test can produce greatly variable data, even within laboratories. 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). This test is also referred to as the two-temperature choice assay or thermal place preference test and can be used to assess both cold or heat avoidance or preference (Moqrich et al., 2005). doi: 10.1258/la.2008.007156, Sandkhler, J. (2010). Researchers can now design experiments around the biological questions rather than the limitations of their animal model. It is plausible that differences in behavior may relate to the type of sensory fiber activated. Joint Bone Spine 72, 359371. These measures can have a profound effect on the apparent anti-nociceptive efficacy of test compounds and should thus be carefully considered during experimental design (Winter and Flataker, 1965). (2009). Different methodological approaches are used to determine mechanical sensitivity using manual Von Frey, including the up-down, ascending stimulus or percent response method, all of which will be discussed below. Here, the rodent is placed on the plate after it has been cooled to the desired temperature and the time taken to evoke nociceptive behavior such as shaking, jumping or licking in the animal is recorded as the response time. doi: 10.1016/0024-3205(84)90575-7, Zimmermann, K., Deuis, J. R., Inserra, M. C., Collins, L. S., Namer, B., Cabot, P. J., et al. Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice. The CatWalk method: assessment of mechanical allodynia in experimental chronic pain. doi: 10.1016/0304-3959(94)90023-x, Colburn, R. W., Lubin, M. L., Stone, D. J. Jr., Wang, Y., Lawrence, D., DAndrea, M. R., et al. A response is considered positive if the animal exhibits any nocifensive behaviors, including brisk paw withdrawal, licking, or shaking of the paw, either during application of the stimulus or immediately after the filament is removed. For example, in the case of application of a stimulus to the hind paw, the investigator must determine if the animal withdrew the hind paw due to its aversive nature, or whether the animal withdrew the hind paw for another reason (e.g., tickle, grooming, ambulation). Eur. A rat model of bone cancer pain. doi: 10.1016/j.ejpain.2004.10.006, Wibbenmeyer, L., Sevier, A., Liao, J., Williams, I., Latenser, B., Lewis, R., et al. Pain 96, 129140. The need for randomization in animal trials: an overview of systematic reviews. It should be noted that rather than flinching or licking, some rat strains tend to simply avoid weight bearing on the affected paw or reposition their stance to minimize contact with the cool surface, so all observation should be adapted to the specific model animal. These values are not absolute, as heat thresholds are influenced by the ambient temperature, rate of heating (110C/s), the type (hairy or glabrous) and location of test skin, method of heat transfer, experimental design and skin temperature (for radiant heat only; Pertovaara et al., 1996; Defrin et al., 2006; Rolke et al., 2006). This assay is based on the hypothesis that a rodent with spontaneous pain will guard the painful paw, leading to changes in its gait (exhibiting a limp or changes in stride size, for instance) in addition to changes in weight bearing (Jacobs et al., 2014). doi: 10.1016/0304-3959(96)03048-5, Quadros, A. U., Pinto, L. G., Fonseca, M. M., Kusuda, R., Cunha, F. Q., and Cunha, T. M. (2015). (A) Manual Von Frey. doi: 10.1590/s0100-879x2006001200013, Gregory, N. S., Harris, A. L., Robinson, C. R., Dougherty, P. M., Fuchs, P. N., and Sluka, K. A. Methods 131, 9397. Activation of opioid receptors in cutaneous nerve endings by conorphin-1, a novel subtype-selective conopeptide, does not mediate peripheral analgesia. It should be noted that no test can therefore measure pain in animals directlythe presumably unpleasant emotional experience of pain is inferred from pain-like behaviors which can include the withdrawal of a body part from a stimulus, reduced ambulation, agitation, an increase in grooming of the affected area, and vocalizations upon sensory stimulation. Adams, B. L., Guo, W., Gors, R. T., and Knopp, K. L. (2016). Ther. doi: 10.1016/j.pain.2010.05.021, Langford, D. J., Bailey, A. L., Chanda, M. L., Clarke, S. E., Drummond, T. E., Echols, S., et al. Exp. Development of a piglet grimace scale to evaluate piglet pain using facial expressions following castration and tail docking: a pilot study. Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice. 53, 2428. Non-response occurs when some subjects do not have the opportunity to participate in the survey. doi: 10.1016/s0304-3959(00)00307-9, Kim, S. H., and Chung, J. M. (1992). Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice. Some results suggest that the rat more accurately reflects human physiology than other species, mimicking human disease more accurately in many cases. The force ramp and paw withdrawal force are displayed by the software post-test. doi: 10.1016/0006-8993(86)91138-8, Jirkof, P., Cesarovic, N., Rettich, A., Nicholls, F., Seifert, B., and Arras, M. (2010). Physiol. As altered weight bearing can be a major symptom of human pain conditions, these tests were developed to improve translation of rodent nociception models to the clinic. doi: 10.1016/j.jneumeth.2015.08.010, Brenner, D. S., Golden, J. P., and Gereau, R. W. IV (2012). 34, 17551762. Life Sci. If there is no response, the next filament with a higher force is tested; if there is a response, the next lower force filament is tested. Increasing temperatures are applied for 10 s from 35C to 70C in intervals of 2.5C until a paw withdrawal behavior is observed (Banik and Kabadi, 2013). The protective role of pain is most evident in individuals who have congenital insensitivity to pain, a rare genetic condition that results in the inability to sense tissue damaging or nociceptive stimuli (Cox et al., 2006). The Dynamic Plantar Aesthesiometer (or Plantar Von Frey), houses rodents in an enclosure with a mesh screen floor, under which a movable touch-stimulator unit is placed. Spontaneous pain can be quantified in humans by asking them to describe their pain using a numeric pain scale (010), visual analog scale (transected line) or verbal scale (no pain to worst pain; Gaston-Johansson et al., 1990; Wibbenmeyer et al., 2011). Some of these behaviors can be sensitive to analgesics, although differences are observed depending on the type of behavior quantified. ECLAM Corporate VP, Veterinary and Professional Services BACKGROUND Laboratory rodents have been used in the United States as research animals since the late 1800s. Pain 20, 231240. This normally protective response, which is absent in these individuals, leads to frequent injuries and often results in higher mortality rates early in life (Bennett and Woods, 2014). Ann. A burrow is placed in the cage of a rodent filled with a suitable substrate (such as food pellets, sand, or marbles). Click the button below to get a quote! 2014. Lab. Exposure of the hind paw to acetone does not evoke paw withdrawal in lightly anesthetized animals (unlike the tail flick assay), while ethyl chloride application achieves skin temperatures approaching 5C or less, and is generally considered a noxious cold stimulus (Leith et al., 2010). While several systems are commercially available, the Dynamic Plantar Aesthesiometer (Ugo Basile) and MouseMet or RatMet (TopCat Metrology) are particularly robust and user-friendly systems. Monkeys, rabbits, cats, ferrets, pigs, sheep and chimpanzees are just some of the animals used for biomedical experiments, science education, and product and cosmetics testing. Front. Ther. (B) Hot plate test. Osteoarthr. As the test is performed in relatively unrestrained rodents, it relies heavily on the animal freely taking up the correct stance, which can be difficult to achieve in mice. The mouse has many similarities to humans in terms of anatomy, physiology and genetics. Similar to the Hargreaves test, the thermal probe tests enables quantification of ipsilateral and contralateral heat thresholds in unrestrained mice, but with a shorter habituation time of 510 min. Mouse model: Pros & Cons. J. Neurotrauma 29, 898904. It is estimated that more than 50 million animals are used in experiments each year in the United States. The 50% threshold is then calculated using the formula: 50% threshold (g) = 10(X+kd)/104, where X = the value (in log units) of the final von Frey filament, k = tabular value for the response pattern (see Appendix 1 in Chaplan et al., 1994) and d = the average increment (in log units) between von Frey filaments. An advantage of this method is that it avoids excessive application of Von Frey filaments that elicit aversive behaviors. Sci. In this test, the unrestrained mouse or rat is placed on a metal surface starting at a non-noxious temperature (<42C), and the temperature is increased at a constant rate until a nocifensive behavior is observed. The same methods that allow this to be so in mice have failed in rats. The severity of these expressions varies with the severity of perceived pain, and is graded on a scale with 0 being normal, 1 being moderately, and 2 being severely changed features. Quantitative somatosensory testing of warm and heat-pain thresholds: the effect of body region and testing method. Temperature 3, 199207. doi: 10.1016/s0140-6736(99)01307-0. doi: 10.1523/JNEUROSCI.2203-07.2007, Yalcin, I., Charlet, A., Freund-Mercier, M. J., Barrot, M., and Poisbeau, P. (2009). Veterinarians are required to inspect the living conditions of the animals. These people will not be included in the survey, and the survey's accuracy will suffer from non-response. Quantitative sensory testing in the german research network on neuropathic pain (DFNS): standardized protocol and reference values. Rodents are allowed to freely move along a liner or circular surface with a temperature gradient. This test can be carried out using the same mouse enclosures as the electronic von Frey test (MouseMet) and is based on the application of a 2 mm thermal probe to the hind paw. While paw withdrawal temperature can be derived from the time to withdrawal (Hargreaves et al., 1988), the actual temperature applied to the skin would need to be experimentally determined by attaching a thermocouple probe to the skin. The tail flick test, first described in 1941, involves application of a heat stimulus to the tail of mice and rats, and the time taken for the tail to flick or twitch is recorded (DAmour and Smith, 1941; Figure 3A). Whether you need help solving quadratic equations, inspiration for the upcoming science fair or the latest update on a major storm, Sciencing is here to help. This review article provides an overview, as well as discussion of the advantages and disadvantages of the most commonly used behavioral methods of stimulus-evoked and non-stimulus-evoked nociception used in rodents. An additional confounding factor in the hot plate test is the tendency for learned behavioral responses, which lead to diminished reaction times during subsequent exposures to the hot plate (Gamble and Milne, 1989; Plone et al., 1996). The three Rs are: Reduction, Refinement, Replacement.. Unlike the tail flick test, the hot plate test and other tests that apply heat stimuli to the hind paws are considered to integrate supraspinal pathways, as rats with spinal transection do not withdraw the hind limbs in the hot plate test (Giglio et al., 2006). An estimated 71% of all NIH grant applications from 2008 to 2015 mentioned the keywords mus musculus, mouse, or mice. While rats tend the habituate quickly (<15 min), mice can take up to an hour or more to settle in the cage before testing can begin, which can be time consuming (Chaplan et al., 1994; Minett et al., 2011). Similarly, if a stimulus is applied that does normally evoke a withdrawal response, but the animal withdraws with an exaggerated response, the animal is considered to have hyperalgesia. The study of nonhuman animals has actually played a huge role in psychology, and it continues to do so today. For detailed protocols of these methods see Minett et al. The rodent is placed in an inclined holder with the hind paws resting on two separate pressure sensors. The clinically translatability of the tail flick test is therefore unclear. The Practical Mouse Despite the advantages rats have over mice as human analogs, mice have dominated the modern genetic and biomedical research landscape. Under the direction of the researcher, the apparatus applies a von Frey (0.5 mm) filament to the plantar surface, increasing the force incrementally (050 g) until the paw withdrawal threshold is reached. (C) Randall-Selitto test (handheld device). Neurosci. Use of dynamic weight bearing as a novel end-point for the assessment of Freunds Complete Adjuvant induced hypersensitivity in mice. (2005). Deacon, R. M. (2006a). 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). They helped shape the ideas of operant conditioning in behaviorism. This therefore provides measure of paw withdrawal threshold on a continual scale, as the force is applied continuously and not in steps. A novel behavioral assay for measuring cold sensation in mice. In the conventional hot plate test the rodent is placed on a metal surface maintained at a constant temperature (in this case 54C) and the time taken to elicit a nocifensive behavior (e.g., hind paw withdrawal or licking) is recorded. Brain Res. A cold stimulus is delivered by applying a cut off syringe filled with dry ice (for temperature ranges of 512C) or wet ice (temperature of 17C) to the glass underneath the paw (Brenner et al., 2012, 2015; Figure 4B).
13840110d2d515487e83b87 disadvantages of using rats in research Share this content
13840110d2d515487e83b87 disadvantages of using rats in researchYou Might Also Like
13840110d2d515487e83b87 disadvantages of using rats in researchhow much does a partner make at kpmg?
13840110d2d515487e83b87 disadvantages of using rats in researchkendrick farris no longer vegan
