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doi: 10.1111/ejn.12643, Tetreault, P., Dansereau, M. A., Dor-Savard, L., Beaudet, N., and Sarret, P. (2011). Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice. Attenuated cold sensitivity in TRPM8 null mice. 95% of all animals used in research are rats because their genetic, biological and behavioral characteristics are so similar to that of humans. opportunities for species-specific behaviour), handling, procedures at daytime in nocturnal species, changes in groups for randomization, and too many male animals caged together. (1980). Woolfe, G., and Macdonald, A. D. (1944). Why use the mouse in research? - YourGenome J. This book provides detailed information on a number of methodologies that can be used in The Rat: A Model Used in Biomedical Research A simple and inexpensive method for determining cold sensitivity and adaptation in mice. Toxicol. A Guide to Research Rodent Housing William J. doi: 10.1523/JNEUROSCI.2203-07.2007, Yalcin, I., Charlet, A., Freund-Mercier, M. J., Barrot, M., and Poisbeau, P. (2009). Methods 25, 241250. While not in routine clinical use, quantitative sensory testing has the potential to improve patient outcomes by classifying pain based on the mechanism and choosing treatments that target that mechanism (Baron et al., 2010; Cruz-Almeida and Fillingim, 2014). 738, 111117. If the response rate is 40% or more (i.e., withdrawal response is elicited in two or more out of five applications) testing stops and the force of the last von Frey filament is designated as the mechanical withdrawal threshold (in this case 2 grams-force). The test begins by assessing the response to a filament estimated to be close to the 50% withdrawal threshold (in this case 1 grams-force). ACS Chem. The three Rs are a set of principles that scientists are encouraged to follow in order to reduce the impact of research on animals. The larger size when compared to mice makes handling, sampling and performing procedures easier. doi: 10.1016/j.pain.2006.01.041, Roughan, J. V., Bertrand, H. G., and Isles, H. M. (2016). doi: 10.1016/s0304-3959(00)00276-1, Defrin, R., Ohry, A., Blumen, N., and Urca, G. (2002). Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing. Similarly, as it cannot be said that the animal feels pain, analgesia and analgesic intervention cannot take placeonly anti-nociception and anti-nociceptive interventions can. They know how to use their own litter tray at home. Facial expressions of mice can be used to score the subjective intensity of pain. Pain 1:36. doi: 10.1186/1744-8069-1-36, Andrews, N., Legg, E., Lisak, D., Issop, Y., Richardson, D., Harper, S., et al. However, as the testing surface can influence the results of von Frey, it is possible that values obtained using MouseMet or RatMet are not directly comparable to other methods (Pitcher et al., 1999). Figure 6.Methods used to assess non-stimulus evoked pain behaviors in rodents. Weight bearing evaluation in inflammatory, neuropathic and cancer chronic pain in freely moving rats. Res. A soft transducer ensures minimal vibration and reduces touch-on responses. FACTS and MYTHS - Animal Research at Stanford Pain 10, 767773. A caveat is, however, that no pain-specific behaviors are captured, leading to potential interference from drug or phenotype effects that could mask nociception, or anti-nociception. Response latencies in the tail-flick test depend on tail skin temperature. 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. doi: 10.1097/BCR.0b013e3182033359. PLoS One 12:e0175839. Burn Care Res. Arch. Cold thresholds in humans can be determined in a similar manner to heat thresholds, where a metal probe is applied to skin that decreases in temperature (usually starting at 32C) until a cooling sensation or pain threshold is reached. 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. All we can possibly learn from high-dose experiments is what might happen in overdose situations. In this experiment, a previously unafraid baby was conditioned to become afraid of a rat. Mol. Anim. 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). Pain 7:37. doi: 10.1186/1744-8069-7-37, Hunskaar, S., Fasmer, O. 47, 810. Neuro Oncol. Dynamic mechanical allodynia and hyperalgesia can be assessed by brushing the skin with a cotton bud, paintbrush or cotton ball, and in the case of allodynia, can be evoked by the brushing of clothing, bed sheets or towels against the skin (Jensen and Finnerup, 2014). Neurosci. Figure 2.Visual representation of the different methodological approaches used to determine mechanical sensitivity using manual Von Frey. doi: 10.1016/j.jneumeth.2004.07.005, Hargreaves, K., Dubner, R., Brown, F., Flores, C., and Joris, J. doi: 10.1038/nature05413, Cruz-Almeida, Y., and Fillingim, R. B. This test involved application of an increasing mechanical force to the surface of the paw or tail until withdrawal or vocalization occurs. Experimenters experienced in the technique are able to distinguish between touch on or false positive responses, however, this can be difficult for inexperienced researchers and extensive training is usually required to produce high quality data. doi: 10.1016/s0140-6736(99)01307-0.