13840110d2d515487e83b87 disadvantages of using rats in research

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. doi: 10.1016/s1474-4422(14)70102-4, Jensen, T. S., Gottrup, H., Sindrup, S. H., and Bach, F. W. (2001). Activation of opioid receptors in cutaneous nerve endings by conorphin-1, a novel subtype-selective conopeptide, does not mediate peripheral analgesia. Ann. 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). Typically, the sensation of warm is elicited at temperatures of 3437C, while the sensation of pain is elicited at temperatures of 4248C (Pertovaara et al., 1996; Defrin et al., 2006; Rolke et al., 2006). Pain 50, 355363. 9, 807819. 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). Rodents are placed individually in small cages with a mesh or barred floor. 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. 39, 18811890. The most common case of bias is a result of non-response. 120, 37603772. 4:165. doi: 10.3389/fnbeh.2010.00165, Kayser, V., and Christensen, D. (2000). An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways. (2009). Tags: CRISPR, CRISPR gene editing, Custom animal model, Share this: doi: 10.1016/j.jphs.2016.01.006, Yeomans, D. C., Pirec, V., and Proudfit, H. K. (1996). In addition to burrowing, other spontaneous behaviors can be assessed, including nesting construction and food hoarding (Deacon, 2006a; Rock et al., 2014). In the past, housing of rodents used for research was designed primarily to prevent Int. The only way to achieve 100 percent accurate results is to survey every single person who uses kitchen cleaners; however, as this is not feasible, you will need to survey as large a sample group as possible. Methods 25, 241250. doi: 10.1016/S0304-3959(01)00437-7, Menndez, L., Lastra, A., Hidalgo, A., and Baamonde, A. Lab. Frontiers | Methods Used to Evaluate Pain Behaviors in Rodents Methods Mol. This falls into one of five main categories: Computer or gaming addiction. Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. The clinical picture of neuropathic pain. A small sample size also affects the reliability of a survey's results because it leads to a higher variability, which may lead to bias. J. Vis. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: behavioral evidence. 9, 8998. Rodent Hypoxia-Ischemia Models for Cerebral Palsy Research: A Systematic Review. 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). J. Pharmacol. Behavioural and electrophysiological characterisation of experimentally induced osteoarthritis and neuropathy in C57Bl/6 mice. (2006). The Hargreaves test permits measurement of ipsilateral and contralateral heat thresholds, allowing each animal to serve as its own internal control in unilateral pain models. The CatWalk method: assessment of mechanical allodynia in experimental chronic pain. Thus, the hot plate test can produce greatly variable data, even within laboratories. (2010). Depending on the species and strain of rodent used, at least 12 different behaviors have been noted in the hot plate test, including sniffing, grooming, stamping of the legs, freezing, licking, leaning and jumping (Espejo and Mir, 1993). Anim. Originally the method was used on rat pups seven days after birth, when their brains are most similar to those of newborn babies. Vet. doi: 10.1016/s1063-4584(03)00163-8, Bradman, M. J., Ferrini, F., Salio, C., and Merighi, A. Nonetheless, consistent measurements are possible in acclimatized animals, although guarding or altered weight distribution may lead to errors. J. Pharmacol. doi: 10.1016/j.ejpain.2004.10.006, Wibbenmeyer, L., Sevier, A., Liao, J., Williams, I., Latenser, B., Lewis, R., et al. To obtain reliable data, animals need to be habituated to the restraint method and experimental apparatus, which can become very time-intensive. 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). PLoS One 9:e104458. 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. Almost all disease-linked human genes have counterparts in the rat. The HomeCageScan (CleverSys) uses automated video analysis to classify 38 pre-defined behaviors of mice in a home cage, including walking, rearing, sniffing, stretching, jumping, digging, foraging, sleeping, eating, drinking, hanging and grooming as well as distance traveled (Roughan et al., 2009). Chronic pain serves no protective purpose, and depending on the severity, can be a debilitating condition that is difficult to treat, with the currently available analgesics often lacking efficacy and suffering dose-limiting adverse effects. 2014. This can be achieved through a variety of techniques. Irwin, S., Houde, R. W., Bennett, D. R., Hendershot, L. C., and Seevers, M. H. (1951). Similarly, human scoring lends itself to bias, although this can be avoided with appropriate randomization, allocation concealment and blind outcome assessment (Hirst et al., 2014). (2011). (2010). 67, 705713. J. A Biol. 738, 111117. doi: 10.1021/acschemneuro.5b00113, Deuis, J. R., Zimmermann, K., Romanovsky, A. "Its brain is larger than that of a mouse, so it's easier to study the structures," said Joyce. Mice and Rats as Laboratory Animals - MSD Veterinary Manual 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. doi: 10.1016/j.jpain.2013.01.770, Ogren, S. O., and Berge, O. G. (1984). A burrow filled with a suitable substrate (such as food pellets, sand, or marbles) is made from a long tube sealed at one end, secured and lifted by screws on the other end to prevent non-burrowing behaviors from displacing the substrate inside (Figure 6B). This work was supported by an Australian Research Council Future Fellowship (IV). ECLAM Corporate VP, Veterinary and Professional Services BACKGROUND Laboratory rodents have been used in the United States as research animals since the late 1800s. doi: 10.1093/gerona/glr210, OBrien, D. E., Brenner, D. S., Gutmann, D. H., and Gereau, R. W. IV (2013). Lancet Neurol. Ethical Considerations in Mouse Experiments - PubMed A method for determining loss of pain sensation. Email: inquiry@genetargeting.com Pain 12:1744806916629049. doi: 10.1177/1744806916629049, Guilford, B. L., Ryals, J. M., and Wright, D. E. (2011). Colver A, Fairhurst C, Pharoah PO. (B) Hot plate test. Pain 96, 129140. Despite some degree of uncertainty about the validity of the anthropomorphization of pain in animals, the capacity to experience pain and distress, particularly resulting from procedures or conditions that would cause pain and distress in humans, must be assumed unless there is evidence to the contrary. 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. Sci. Animal studies in psychology - American Psychological Association 1, 118121. Lett. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. For example, in a rat model of carrageenan-induced inflammation, significantly altered plate preference was only observed for temperatures of 15C and 45C relative to the test plate maintained at 25C (Balayssac et al., 2014). 89% of scientists surveyed by the Pew Research Center were in favor of animal testing for scientific research. doi: 10.1016/s0165-0270(03)00241-3, Balayssac, D., Ling, B., Ferrier, J., Pereira, B., Eschalier, A., and Authier, N. (2014). FACTS and MYTHS - Animal Research at Stanford Randall, L. O., and Selitto, J. J. However, this requires the animals to be acclimatized to the apparatus to minimize ambulation so that withdrawal latencies can be accurately determined. While the underlying protocols and principles are different, it remains to be determined if electronic Von Frey activates a different subset of sensory neurons compared to manual Von Frey (e.g., high-threshold vs. low threshold mechanoreceptors). Pain measurement: an overview. J. Neurosci. (2011). Rodents are allowed to freely move along a liner or circular surface with a temperature gradient. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a. doi: 10.1089/neu.2010.1700, Scholz, J., Broom, D. C., Youn, D. H., Mills, C. D., Kohno, T., Suter, M. R., et al. J. Neurosci. DAmour, F. E., and Smith, D. L. (1941). Pain 10, 767773. Ishikawa, G., Nagakura, Y., Takeshita, N., and Shimizu, Y. In the cold plantar assay, the animal is placed in an enclosure with a clean glass floor. doi: 10.1016/0006-8993(86)91138-8, Jirkof, P., Cesarovic, N., Rettich, A., Nicholls, F., Seifert, B., and Arras, M. (2010). A Guide to Research Rodent Housing William J. 34, 17551762. doi: 10.1038/nrn2606, Moqrich, A., Hwang, S. W., Earley, T. J., Petrus, M. J., Murray, A. N., Spencer, K. S., et al. A major advantage of the thermal probe test is the reduced time required for acclimatization to the testing environment, enabling characterization of models or compounds with short duration of action, as well as testing of mechanical and thermal thresholds in the same enclosure. Methods 87, 185193. However, rodents do not vocalize in the audible range unless the pain is severe, making use vocalization as an endpoint ethically limited (Mogil, 2009). The ascending stimulus method provides an estimate of the mechanical withdrawal threshold. Behav. Stimulus-evoked methods, which include manual and electronic von Frey, Randall-Selitto and the Hargreaves test, were the first to be developed and continue to be in widespread use. Optimization of the mechanical nociceptive threshold testing with the Randall-Selitto assay. The test is carried out on mesh floor and acetone is dabbed or sprayed on the plantar surface of the hind paw (Figure 4A), eliciting cooling of the skin to innocuous temperatures of 1521C (Colburn et al., 2007; Leith et al., 2010), although the actual temperature varies with ambient temperature, skin temperature, and the amount of acetone applied. 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. 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. J. Pharmacol. Sci. Finally, whisker change refers to change in whisker position (may be backward, forward, or clumped together). A simple and inexpensive method for determining cold sensitivity and adaptation in mice. A burrow is placed in the cage of a rodent filled with a suitable substrate (such as food pellets, sand, or marbles). J. Pharmacol. 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. Mechanical pressure is applied focally to the dorsal or plantar surface of the hind paw or tail, which is placed between a pointed probe tip and a flat surface. 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. Rats as Pets Pros and Cons - HRF While forepaw withdrawal often occurs first, hind paw withdrawal or licking is considered to be a more reliable indicator of nociception, as the forepaws are frequently used in grooming and exploration and are not consistently in contact with the metal surface (Woolfe and Macdonald, 1944; Minett et al., 2011). Characterization of the foot withdrawal response to noxious radiant heat in the rat. Non-response occurs when some subjects do not have the opportunity to participate in the survey. Significant determinants of mouse pain behaviour. Scientists often cite the similarities between animals and humans as the rationale for animal experimentation. Res. Constraints on the tailflick assay: morphine analgesia and tolerance are dependent upon locus of tail stimulation. A radiant or infrared heat source is positioned underneath the animal and aimed at the plantar surface of the hind paw (Figure 3C). (D) Thermal probe test. Although animal research may have ethical concerns, the US has regulated its practice since 1966. It should be noted that the paw withdrawal threshold can be considered a measure of spinal reflex, with some researchers favoring vocalization as an end-point (Winter and Flataker, 1965; Kayser and Christensen, 2000; Santos-Nogueira et al., 2012). 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. Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain. 7. This shift was primarily instigated by the availability of a much . 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). The acetone evaporation test, first described in 1994, is a technique used to measure aversive behaviors triggered by evaporative cooling and is typically considered as a measure of cold allodynia (Carlton et al., 1994; Choi et al., 1994; Vissers and Meert, 2005). Nose bulge refers to the bulge noticeable on the bridge of the nose, whereas cheek bulge refers to the rounded projection of the cheek muscle compared to its typical appearance. is defined as the deposition of in renal tissue, although a variety of additional terms are sometimes employed to reflect the localization of the mineral in the cortex, medulla, and so on. If you've taken an introductory psychology class, then you have probably read about seminal psychological research that was done with animals: Skinner's rats, Pavlov's dogs, Harlow's monkeys. When rodents are unwell, the amount of material removed from the burrow is decreased. BBC - Ethics - Animal ethics: Experimenting on animals Obviously this cannot be done in rodents, making spontaneous pain difficult to quantify; however new methods to evaluate spontaneous pain are increasingly being reported, including grimace scales, burrowing assays, gait analysis, weight bearing and automated behavioral analysis (for a summary on behavioral tests used in non-stimulus evoked nociception, see Tappe-Theodor and Kuner, 2014). Evaluation of dynamic weight bearing for measuring nonevoked inflammatory hyperalgesia in mice. J. Pharmacol. B., and Hole, K. (1985). 2023 Leaf Group Ltd. / Leaf Group Media, All Rights Reserved. Experimental Rat - an overview | ScienceDirect Topics J. Neurosci. Pain Med. 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. Novel use of perineural pregabalin infusion for analgesia in a rat neuropathic pain model. This sample group should include individuals who are relevant to the survey's topic. 43, 1726. Exp. Skinner's Box Experiment | Behaviorism | Practical Psychology Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Protoc. The Laboratory Rat - 3rd Edition - Elsevier Pain is a multifaceted and diverse experience that can be categorized into a number of types and modalities, depending on the presentation and triggering stimulus of the pain event. In this test, monofilaments of varying forces (in this case 0.6, 1, 1.4, 2, 4 and 6 grams-force) are applied in ascending order an equal number of times (in this case five times) and the response to each trial is recorded. Adams, B. L., Guo, W., Gors, R. T., and Knopp, K. L. (2016). The Kantian view denies moral value to animals because they lack reason. Methods 255, 92103. Methods 219, 4151. Neurosci. The distinction between nociception and pain thus underlines a key difference in terminology when referring to communicating and non-communicating subjects. (2000). Nonetheless, the thermal probe test remains to be validated in other pain models that cause more pronounced mechanical allodynia. Unfortunately, many introductory . According to the replacement principle, the use of live animals should be replaced with in vitro or computational methods where possible, and if unavoidable, the use of non-sentient or less sentient animals is preferred. doi: 10.1016/j.pain.2013.05.032, Dixon, W. J. Handling and restraint: General principles | NC3Rs At least six responses around the estimated threshold are required for optimal calculation of the 50% threshold (Dixon, 1980). Pain 150, 340350. Sensory determinants of thermal pain. An additional advantage of the acetone drop test is the unilateral application of the thermal stimulus, enabling comparison to the contralateral side in unilateral models, and a perhaps more ethical stimulus in bilateral models. This test involved application of an increasing mechanical force to the surface of the paw or tail until withdrawal or vocalization occurs. In this experiment, a previously unafraid baby was conditioned to become afraid of a rat. doi: 10.1038/nprot.2006.19, Decosterd, I., and Woolf, C. J. In 2016 about 486,000 patients with burns in the United States presented to emergency departments 1; of which, 30,000 patients were admitted to one of the 128 burn centers in the United States. While validated using an incisional model of pain in rats, this method takes longer to perform than the normal Hargreaves test and is not available to purchase commercially. (2016). It should be noted that the absolute values obtained using manual and electronic Von Frey can differ significantly. 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. Anesth. The experiment begins by testing the response to a filament estimated to be close to the 50% withdrawal threshold. However, with the use of animal models come challenges relating to the appropriate quantification of behavioral responses that could be considered equivalent to pain in humans. Woolfe, G., and Macdonald, A. D. (1944). Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin. Cooling of the glass leads to unilateral exposure of the hind paws to a cooled surface, the temperature of which can be determined by attaching a thermocouple probe to the glass or skin. J. Neurosci. 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. 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. 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. The use of ultrasonic (inaudible) vocalization as an endpoint has also been studied, however it has not consistently been shown to increase in response to noxious stimuli (Han et al., 2005; Wallace et al., 2005; Williams et al., 2008). Gait analysis of C57BL/6 mice with complete Freunds adjuvant-induced arthritis using the CatWalk system. (2017). Pain 87, 149158. doi: 10.1016/0160-5402(91)90014-v, Touska, F., Winter, Z., Mueller, A., Vlachova, V., Larsen, J., and Zimmermann, K. (2016). Cartil. Adult mice multiply quickly. J. 97:e52640. Behaviors that are analyzed include locomotive activity (still, walking, trotting, running), distance traveled, velocity, grooming, posture, eating/drinking and foraging. Pain 9, 445452. Sci. 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. Front. Wistar rats are big rats. Ear position denotes the ears being pulled back and apart from their standard position (may feature vertical ridges). This alleviates the mosaicism common with targeting embryos, allowing for the production of specifically targeted germline rats in as little as 3 months. Water heated to 30C and applied the same way is usually used as a control (Carlton et al., 1994; Choi et al., 1994). Ultrasound vocalisation by rodents does not correlate with behavioural measures of persistent pain. (C) Weight bearing (incapacitance test). (2013). Becoming overdependent and even addicted to our gadgets is another of the main disadvantages in technology. 1. If an individual is on a company's website, then it is likely that he supports the company; he may, for example, be looking for coupons or promotions from that manufacturer. Differentiating thermal allodynia and hyperalgesia using dynamic hot and cold plate in rodents. Pain studies in humans are difficult to perform, are subjective, and are limited by ethical considerations, leading to the widespread use of animals as models to study pain, with the most commonly used species being mice and rats (Mogil, 2009). (2009). Assessment of pain and itch behavior in a mouse model of neurofibromatosis type 1. doi: 10.1080/23328940.2015.1135689, Vazquez, G., Alvarez, E., and Navaza, J. M. (1995). J. Clin. Mol. 43, 207213. 16, 13241332. While such behavioral changes may correlate to thermal allodynia or hyperalgesia, the contribution of additional sensations or complex behaviors to the preferred environmental temperature cannot be ruled out. doi: 10.1111/j.1749-6632.1983.tb53494.x, Espejo, E. F., and Mir, D. (1993). 43, 244258. Hyperalgesia is defined as an increased or exaggerated pain response to a normally noxious stimulus, while allodynia is defined as a painful response to a normally non-noxious or innocuous stimulus. 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). Cybersex and pornography addiction. Mol. Data 40, 611614. Simmons has worked as a freelance writer since 2009. A wide variety of other species make up the remaining 4%, from . The software records the duration of different behavior types, including movement, grooming and rearing behaviors. An estimated 71% of all NIH grant applications from 2008 to 2015 mentioned the keywords mus musculus, mouse, or mice. 6, 17511758. In addition, skin and ambient temperature, the location of stimulus application on the tail, as well as learnt avoidance behaviors can affect the withdrawal response (Yoburn et al., 1984; Berge et al., 1988).
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