13840110d2d515487e83b87 disadvantages of using rats in research

In the case of rats specifically, their particular DNA and physiology has allowed scientists to explore a variety of physiological and pathophysiological mechanisms that would not be possible in a mouse model. doi: 10.1093/ilar.43.4.244, Gabriel, A. F., Marcus, M. A., Walenkamp, G. H., and Joosten, E. A. In contrast to other Von Frey setups, animals are housed in individual enclosures with bars, rather than mesh, to help maximize the surface area of the hind paw available for application of the filament. Brain Res. (2017a). Behav. 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). It is a low-cost, single-use product made from sterilized quarry sand and treated with a hydrophobic coating. The criterion that constitutes a positive response to a filament varies between laboratories, with 20%40% withdrawal response rates over 510 applications being used typically (Scholz et al., 2005; Minett et al., 2011). This sample group should include individuals who are relevant to the survey's topic. Nurs. Rats are an ideal choice for many labs due to their physiological similarity to humans. doi: 10.1016/j.neulet.2012.07.017. Temperature 3, 199207. In humans, acute pain is defined as short-lasting (36 months) and is directly related to injury or tissue damage, such as a cut, burn or broken bone. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. Age-related neurodegenerative diseases are largely limited to humans and rarely occur spontaneously in animals. This falls into one of five main categories: Computer or gaming addiction. J. Neurosci. The larger size when compared to mice makes handling, sampling and performing procedures easier. Cartil. Unilateral hot plate test: a simple and sensitive method for detecting central and peripheral hyperalgesia in mice. 43, 244258. Xing, H., Chen, M., Ling, J., Tan, W., and Gu, J. G. (2007). Sample size determination. J. Neurosci. doi: 10.1111/j.1749-6632.1983.tb53494.x, Espejo, E. F., and Mir, D. (1993). Neurosci. 1. | All rights reserved. Phone: +1 (631) 468-8530 To conduct a survey properly, you need to determine your sample group. doi: 10.1016/j.joca.2015.05.001, Buys, M. J., and Alphonso, C. (2014). Disord. Analgesic treatment of ciguatoxin-induced cold allodynia. This suggests that the tail flick response may be impacted by changes in motor processing (Chapman et al., 1985). Almost all disease-linked human genes have counterparts in the rat. Burns 43, 304309. Pain 68, 133140. In addition, the experimental time is dramatically reduced, as few applications (usually 34) are needed to determine the paw withdrawal threshold (Deuis et al., 2014, 2015). In fact, it is a requirement for publication of in vivo data in high quality journals that relevant standards and guidelines are strictly adhered to (McGrath et al., 2010). Assoc. Pain 123, 231243. 406, 128132. This problem can be overcome by restraining the rodent and only placing the plantar surface of a one hind paw on the metal surface and recording the time to withdrawal, however this method requires significant handling and associated stress (Menndez et al., 2002). Methods used to assess mechanically evoked pain like behaviors in rodents. Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. doi: 10.1016/S0304-3959(01)00437-7, Menndez, L., Lastra, A., Hidalgo, A., and Baamonde, A. Pain measurement: an overview. The dynamic weight-bearing test is able to detect reduced weight bearing behaviors of the affected hind limb in multiple pain models, including CFA-induced inflammation, chronic constriction injury, bone cancer pain and antigen-induced arthritis (Tetreault et al., 2011; Robinson et al., 2012; Quadros et al., 2015). doi: 10.1523/JNEUROSCI.2203-07.2007, Yalcin, I., Charlet, A., Freund-Mercier, M. J., Barrot, M., and Poisbeau, P. (2009). The term nociception was coined by Charles Sherrington in the early 1900s to distinguish the sensation of paina result of central nervous system processingfrom the physiological phenomenon of the peripheral nervous system responding to potential harmful stimuli (Dubner, 1983; Coutaux et al., 2005). In addition, welfare benefits in form of testing of unrestrained mice and exposure of only a single hind paw to a noxious heat stimulus are favorable. The Hargreaves test is usually carried out using a glass bottom enclosure, which can be heated to minimize errors arising from heat sink effects. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a. Methods 219, 4151. doi: 10.1177/0023677214559084, Minett, M. S., Eijkelkamp, N., and Wood, J. N. (2014). Scientists recovered most of the Christmas Island rat's genome. A simple and inexpensive method for determining cold sensitivity and adaptation in mice. doi: 10.1016/j.jneumeth.2004.07.005, Hargreaves, K., Dubner, R., Brown, F., Flores, C., and Joris, J. Similarities in pain descriptions of four different ethnic-culture groups. doi: 10.1093/ilar.43.4.207, Deuis, J. R., Dekan, Z., Wingerd, J. S., Smith, J. J., Munasinghe, N. R., Bhola, R. F., et al. J. Monofilaments of differing forces are applied perpendicularly to the hind paw. 13, 924935. Neurosci. If the response rate is less than 40% (i.e., a withdrawal response is elicited in none or one out of five applications) the next filament is tested. Pain 22, 130136. Three main ethical attitudes towards animals are reviewed here. 95% of animals used in experiments are not protected by the federal Animal Welfare Act (AWA), which excludes birds, rats and mice bred for research, and cold-blooded animals such as reptiles and most fish. (2007). Analgesic effects of clinically used compounds in novel mouse models of polyneuropathy induced by oxaliplatin and cisplatin. Despite these advantages of automation, experimenters still need to be experienced to distinguish true responses from touch-on responses and ambulation. J. Neurosci. ingenious was very competitively priced compared to other reputable transgenic companies. Mechanical hyperalgesia and allodynia can be further subdivided into dynamic (triggered by brushing), punctate (triggered by touch) and static (triggered by pressure). Protoc. However, as animals cannot be said to be reporting pain, any reaction to such stimuli does not necessarily evidence experience of pain (Sandkhler, 2009). doi: 10.1371/journal.pone.0175839, Han, J. S., Bird, G. C., Li, W., Jones, J., and Neugebauer, V. (2005). For example, paw licking is diminished by opioids but not other analgesics, while other behaviors can also be affected by other classes of analgesics (Ankier, 1974; Hunskaar et al., 1985). Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. The device automatically records the temperature that paw withdrawal occurred (in this case 50C). The software records the duration of different behavior types, including movement, grooming and rearing behaviors. Pain 5:18. doi: 10.1186/1744-8069-5-18, Hirst, J. Of acute wounds, burns are one of the most devastating injuries known to mankind. - J. Braz. Readership. Sci. 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. Gene editing technologies allow scientists to use rats more often in their research. 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. Rodents may also respond to initial contact with a filament with a touch-on response. doi: 10.3791/52640, Brodkin, J., Frank, D., Grippo, R., Hausfater, M., Gulinello, M., Achterholt, N., et al. New hot plate tests to quantify antinociceptive and narcotic antagonist activities. However, replacement or substitution of animals for nonsentient materials is difficult in pain research due to the nature of the behavioral experiments. Irwin, S., Houde, R. W., Bennett, D. R., Hendershot, L. C., and Seevers, M. H. (1951). 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. doi: 10.1016/0304-3959(94)90090-6, Carter, R. B. Thus, the hot plate test can produce greatly variable data, even within laboratories. doi: 10.1093/neuonc/nou048, Deuis, J. R., and Vetter, I. Testing should also be avoided while the animal is engaged in grooming behaviors, as this can produce false negative responses. (2010). doi: 10.1016/j.pain.2013.06.015, Keywords: pain, rodent, hyperalgesia, allodynia, spontaneous pain, mechanical, heat, cold, Citation: Deuis JR, Dvorakova LS and Vetter I (2017) Methods Used to Evaluate Pain Behaviors in Rodents. Assessing hoarding in mice. Neurosci. White, V.M.D., M.S., DACLAM, Dipl. Static weight bearing or incapacitance assays measure the distribution of weight across the hind paws and typically involve placing the animal in an inclined holder forcing placement of the hind paws on two independent pressure sensors (Figure 6C). Behav. doi: 10.1097/01.ajp.0000154048.68273.d8, Dell, R. B., Holleran, S., and Ramakrishnan, R. (2002). 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. Lab. The Practical Mouse Despite the advantages rats have over mice as human analogs, mice have dominated the modern genetic and biomedical research landscape. The Rat Grimace Scale is able to detect spontaneous pain induced by intraarticular kaolin-carrageenan, intraplantar Complete Freunds Adjuvant (CFA), and post-surgical pain. (2016). doi: 10.1371/journal.pone.0125822, Lu, R., and Schmidtko, A. J. doi: 10.1016/j.jneumeth.2013.06.005, Baron, R., Binder, A., and Wasner, G. (2010). 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. Adams, B. L., Guo, W., Gors, R. T., and Knopp, K. L. (2016). This raises a moral issue in animal experimentation. Protoc. A phobia is an irrational fear, that is out of proportion to the danger. doi: 10.1016/0160-5402(91)90014-v, Touska, F., Winter, Z., Mueller, A., Vlachova, V., Larsen, J., and Zimmermann, K. (2016). Am. Wistar rats are big rats. Meloxicam prevents COX-2-mediated post-surgical inflammation but not pain following laparotomy in mice. Response latencies in the tail-flick test depend on tail skin temperature. Osteoarthr. Anim. The experiment begins by testing the response to a filament estimated to be close to the 50% withdrawal threshold. *Correspondence: Irina Vetter, i.vetter@uq.edu.au, View all Biol. (2013). Computerized analysis of audible and ultrasonic vocalizations of rats as a standardized measure of pain-related behavior. (1957). For example, in models of burn pain, chemotherapy-induced neuropathy, and intra-articular carrageenan, changes in mechanical allodynia as measured by Von Frey and changes in gait parameters do not always correlate (Gabriel et al., 2009; Boehmerle et al., 2014; Yin et al., 2016; Deuis et al., 2017b). Pain 9, 445452. (A) Grimace scales. Neuropharmacology 23, 915924. doi: 10.1038/nprot.2006.171, Deacon, R. M. (2006b). J. The spectrometer is capable of recording 23 different types of behaviors in real time, including ambulation (still, walking, trotting, running), grooming behaviors, and rearing behaviors, as well as distance traveled and average velocity (Brodkin et al., 2014). (2011). Stimulus-evoked pain can be evaluated in humans using quantitative sensory testing. doi: 10.1016/j.burns.2016.09.001, Deuis, J. R., Lim, Y. L., Rodrigues de Sousa, S., Lewis, R. J., Alewood, P. F., Cabot, P. J., et al. 524, 107110. Phenotypic changes in diabetic neuropathy induced by a high-fat diet in diabetic C57BL/6 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. Rep. 5:14648. doi: 10.1038/srep14648. Abstract The laboratory rat was the first mammal domesticated for research purposes. The sequenced genome will also unveil new targets for drug intervention. Non-response occurs when some subjects do not have the opportunity to participate in the survey. A., Howick, J., Aronson, J. K., Roberts, N., Perera, R., Koshiaris, C., et al. Arthritis Rheum. To quantify temperature sensitivity, the time the animal spends on the test plate relative to the reference plate is measured over a set period and is then compared to control animals. Mouse Biol. 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. Consistent application of acetone can be challenging, as acetone has a lower surface tension than water (25.2 mN/m and 72.8 mN/m respectively), making it difficult to form uniform drops with a pipette or syringe (Vazquez et al., 1995), with some laboratories opting to use a spray instead (Yamamoto et al., 2016). This book condenses information from many sources on topics related to the care and use of rats in research. The Randall-Selitto test can be performed using bench-top (e.g., Analgesy-Meter, Ugo Basile; Paw and Tail Pressure Meter; Harvard Apparatus) or hand-held devices (e.g., Paw Pressure Test Apparatus, IITC) with animals either restrained in a hammock that provides access to the hind paws, a towel, or in a plastic cone or cylinder. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Data quality is usually improved if the time to occurrence of any behavior, rather than specific behavior types, is recorded, and if lower temperatures are used (Carter, 1991; Plone et al., 1996). Efficient analysis of experimental observations. | 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. J. Pharmacol. In its simplest form, the animal can choose between two adjacent areas maintained at different temperatures. doi: 10.1016/j.ejpain.2011.07.012, Ankier, S. I. Repeated exposure to sham testing procedures reduces reflex withdrawal and hot-plate latencies: attenuation of tonic descending inhibition? The force at which this response occurs is recorded automatically by the apparatus and is designated as the paw withdrawal threshold. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. The advantage of this approach is that each animal receives the same number and type of stimuli, although the number of tests per hind paw could exceed 50 (e.g., five different von Frey filaments each applied 10 times), which is not only time consuming, but potentially exposes animals with mechanical hind paw sensitivity to a disproportionate number of more aversive stimuli. Importantly, the pain appears to be spontaneous, with no identifiable stimulus. Boehmerle, W., Huehnchen, P., Peruzzaro, S., Balkaya, M., and Endres, M. (2014). Methods Mol. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Animals are stressed - there are many reasons for stress in the animals: transportation, insufficient time for adapting, cages without enrichment (e.g. Mice are placed individually in small cages with a barred floor. J. Med. They helped shape the ideas of operant conditioning in behaviorism. 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. The evaluation of the analgesic action of pethidine hydrocholoride (Demerol). The power of mouse models proved to be so clear however that the same abilities in rat continued to be desired and pursued. 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. 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). As the animal is unaware of the researcher and neither needs to be restrained or trained, this technique eliminates operator subjectivity and reduces animal stress. Pain Headache Rep. 18:456. doi: 10.1007/s11916-014-0456-x, Jensen, T. S., and Finnerup, N. B. This sample - and the results - are biased, as most workers are at their jobs during these hours. However the distinction between stimulus-evoked and non-stimulus evoked pain may be difficult to make clinically, as arguable it could be allodynia occurring from an unidentified stimulus. The study of nonhuman animals has actually played a huge role in psychology, and it continues to do so today. Similarly, the terms nociception and pain are often used interchangeably, although the term pain is rarely appropriate to use in reference to animal studies. 97:e52640. The hypoxia-ischemia model, first published in 1981, has brain damage similar to that observed in cerebral palsy patients. Thus, pain is an experience that encompasses both sensory and emotional components; therefore the term pain is not interchangeable with nociception. A touch-on reaction is more likely to occur if the filament is not applied perpendicularly, if the filament is not applied smoothly, or if the filament moves horizontally during application, inducing scratching. J. Neurosci. Unequal weight distribution between the ipsilateral and contralateral paw are interpreted as a natural adjustment to the degree of nociception experienced, and have been observed in a number of models including monosodium iodoacetate (MIA)-induced osteoarthritis, bone cancer-induced pain, carrageenan-induced inflammation and sciatic nerve crush injury (Schtt et al., 1994; Medhurst et al., 2002; Bove et al., 2003; Buys and Alphonso, 2014). Therefore, the results of the survey will be skewed to reflect the opinions of those who visit the website. (B) Continuous temperature gradient assay. Burn Care Res. doi: 10.1146/annurev.pa.20.040180.002301, Dubin, A. E., and Patapoutian, A. Behavioral measures of pain thresholds. doi: 10.1016/j.jpain.2013.01.770, Ogren, S. O., and Berge, O. G. (1984). 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). Quantitative sensory testing in the german research network on neuropathic pain (DFNS): standardized protocol and reference values. The exception is use of the test on the tail of mice (Minett et al., 2014), although this may not be useful to assess nociceptive behaviors in commonly used models that are localized to the hind paw. Exp. Facebook Direct intrathecal drug delivery in mice for detecting in vivo effects of cGMP on pain processing. The thermal probe test: a novel behavioral assay to quantify thermal paw withdrawal thresholds in mice. J. Pharmacol. Now, researchers no longer have to choose between the anatomical advantages of rats and the genetic tractability of mice, due to new methods for introducing genetic modifications into the rat genome. 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. Pain 7:37. doi: 10.1186/1744-8069-7-37, Hunskaar, S., Fasmer, O. Accordingly, as pain cannot be directly measured in rodents, it has been necessary to develop indirect methods to quantify and evaluate pain-like behaviors in non-anesthetized animals which are reliable, reproducible, sensitive and specific (Mogil, 2009). The framework for these standards and guidelines are based on the principles of the 3Rs (replacement, reduction, refinement). In terms of the diseases that they are used to study, rats are usually not the model of choice when it comes to disorders related to neoplasms, blood and immune function. (B) Burrowing assay. Methods 113, 9197. 6, 17511758. opportunities for species-specific behaviour), handling, procedures at daytime in nocturnal species, changes in groups for randomization, and too many male animals caged together. Rats have since been used to answer a wide range of basic science questions related to common human diseases in the fields of physiology, immunology, pharmacology, toxicology, nutrition, behavior and learning. The purpose of pain in the above cases is to alert an individual to withdraw from immediate tissue damaging stimuli and to prevent further damage to the site of injury during the healing process. While the Randall-Selitto test often results in similar types of outcomes to the Von Frey filament tests (Santos-Nogueira et al., 2012), the mechanical stimulation differs fundamentally from Von Frey filaments, which may also activate low-threshold mechanoreceptors in addition to nociceptors. 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. (2014). The rat had historically been the preferred animal model for biomedical research due to genetic and physiological similarities to humans. The mouse has many similarities to humans in terms of anatomy, physiology and genetics. Ear position denotes the ears being pulled back and apart from their standard position (may feature vertical ridges). Tags: CRISPR, CRISPR gene editing, Custom animal model, Share this: In line with this, the uptake of grimace scales to study pain in the scientific community has been low, with approximately 30 studies published using the method in rodents since its introduction by Langford et al. Models and mechanisms of hyperalgesia and allodynia. Studying ongoing and spontaneous pain in rodentschallenges and opportunities. A rat model of bone cancer pain. (2015). 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. Animal models of pain: progress and challenges. The most common case of bias is a result of non-response. Its characterized primarily by motor impairment, but there are also a range of accompanying conditions such as seizure disorders and cognitive defects. Lab. Randall, L. O., and Selitto, J. J. Toxicol. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Figure 4.Methods used to assess cold-evoked pain like behaviors and temperature preference in rodents. Osteoarthr. The Randall-Selitto or paw pressure test was developed as a tool to assess response thresholds to mechanical pressure stimulation and is often considered a measure of mechanical hyperalgesia (Figure 1C; Randall and Selitto, 1957). Constraints on the tailflick assay: morphine analgesia and tolerance are dependent upon locus of tail stimulation. 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. 56, 171176. In addition to burrowing, other spontaneous behaviors can be assessed, including nesting construction and food hoarding (Deacon, 2006a; Rock et al., 2014). (C) Hargreaves test. Simmons has worked as a freelance writer since 2009. Non-response occurs when some subjects do not have the opportunity to participate in the survey. Automated behavioral analysis can be performed in a dedicated apparatus (Behavioral Spectrometer, Behavioral Instruments) or in a home cage (HomeCageScan, CleverSys; PhenoTyper, Noldus), using automated video analysis, vibration sensors, photobeams, and combinations thereof. The time taken to flick or withdraw the tail from the heat stimulus is recorded. Ther. 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). Using the horse grimace scale (HGS) to assess pain associated with acute laminitis in horses (Equus caballus). Our goal is to make science relevant and fun for everyone. 7. doi: 10.1016/0304-3959(94)90051-5, Yeomans, D. C., and Proudfit, H. K. (1996). J. Vis. Figure 1. doi: 10.1523/JNEUROSCI.1526-05.2005, Schtt, E., Berge, O. G., Angeby-Mller, K., Hammarstrm, G., Dalsgaard, C. J., and Brodin, E. (1994). 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. The need for randomization in animal trials: an overview of systematic reviews. Surface tension of alchol water + water from 20 to 50 degrees celcius. 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). Researchers and scientists conducting surveys and performing experiments must adhere to certain procedural guidelines and rules in order to insure accuracy by avoiding sampling errors such as large variability, bias or undercoverage. Unfortunately, no accurate figures are available to determine precisely how many animals are used in experiments in the U.S. or worldwide. (2009). Life Sci. (C) Randall-Selitto test (handheld device). Pain 88, 5360. J. Musculoskelet. doi: 10.1016/j.jneumeth.2013.12.010, Bryden, L. A., Nicholson, J. R., Doods, H., and Pekcec, A. (B) Electronic von Frey (MouseMet, TopCat Metrology). Neurosci. Practical mechanical threshold estimation in rodents using von Frey hairs/Semmes-Weinstein monofilaments: towards a rational method. Winter, C. A., and Flataker, L. (1965). J. One way to evaluate nociception in non-communicating subjects is through observation of behavior. Cerebral palsy. J. Pharmacol. Behaviors tend to occur on a spectrum of intensity, but are usually scored in binary as either present or absent. Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin. It's a little like tossing a rat into a vat of gasoline and then concluding that gasoline causes drowning. Exp. doi: 10.1371/journal.pone.0039765, Brenner, D. S., Golden, J. P., Vogt, S. K., and Gereau, R. W. (2015). B., and Hole, K. (1985). J. Neurosci. Prior to the development of automated digitized platforms, this test was performed by coloring the animals paws with ink; the animal was then allowed to walk freely on a paper, which could be scanned for analysis (Ishikawa et al., 2014). 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. (2011). The behavioral methods used to measure nociception in rodents can be divided into stimulus-evoked (and further subdivided by the stimulus modalitymechanical, heat, cold) and non-stimulus evoked, with the most commonly used methods discussed in this review article. This sample group should include individuals who are relevant to the survey's topic. In the conventional hot plate test, an unrestrained mouse or rat is placed on a metal surface maintained at a constant temperature, usually between 50C and 55C, and the response latency, which is the time taken to observe a nocifensive behavior, is recorded by the investigator (Figure 3B). ILAR J. Eur. (1988). McGrath, J. C., Drummond, G. B., McLachlan, E. M., Kilkenny, C., and Wainwright, C. L. (2010). This test involved application of an increasing mechanical force to the surface of the paw or tail until withdrawal or vocalization occurs. Mouse Model: Pros and Cons Ankita Das Chetana Tamadaddi Prashant Waiker Indian Institute of Science Education & Research Bhopal ; MOUSE : Mammalian model organism ; Genome Mammalian 20 chromosomes 2.6 Gb ~25000 genes 99% have human counterpart Strains Inbred Outbred Recombinant inbred Consomic Fluorescent Life Cycle 4-day oestrus 20-day gestation 4-8 pups per litter 2 .

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