In this test, animals are placed individually in small cages with a mesh or otherwise penetrable bottom. Spinal processing of noxious and innocuous cold information: differential modulation by the periaqueductal gray. ECLAM Corporate VP, Veterinary and Professional Services BACKGROUND Laboratory rodents have been used in the United States as research animals since the late 1800s. Oxaliplatin administration increases expression of the voltage-dependent calcium channel 2-1 subunit in the rat spinal cord. Lancet 383(9924): 1240-9. Accordingly, translation of research using experimental nociceptive assays to pain treatment in the clinic has met with some difficulties. 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. 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). doi: 10.3791/52640, Brodkin, J., Frank, D., Grippo, R., Hausfater, M., Gulinello, M., Achterholt, N., et al. Figure 2.Visual representation of the different methodological approaches used to determine mechanical sensitivity using manual Von Frey. 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/S0304-3959(01)00437-7, Menndez, L., Lastra, A., Hidalgo, A., and Baamonde, A. 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). Painful and painless channelopathies. doi: 10.1016/j.physbeh.2011.05.015, Tjolsen, A., Rosland, J. H., Berge, O. G., and Hole, K. (1991). 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). Eur. 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). Behavioral measures of pain thresholds. Methods 25, 241250. The sheep grimace scale as an indicator of post-operative distress and pain in laboratory sheep. Pinpointing these should help researchers to develop rat genetic models of human disease. Burrowing behavior as an indicator of post-laparotomy pain in mice. ILAR J. Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Of acute wounds, burns are one of the most devastating injuries known to mankind. J. Pharmacol. (2016). Methods 219, 4151. A number of endpoints can be obtained from the cold plate test, similar to the hot plate test. Picking up rats by the tail is stressful and should be avoided . 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. Rodent Hypoxia-Ischemia Models for Cerebral Palsy Research: A Systematic Review. These behavioral methods can be divided into stimulus-evoked or non-stimulus evoked (spontaneous) nociception, based on whether or not application of an external stimulus is used to elicit a withdrawal response. (1957). Berryman, E. R., Harris, R. L., Moalli, M., and Bagi, C. M. (2009). Adult mice multiply quickly. J. Neurosci. 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). The manual Von Frey test, developed by the physiologist Maximilian von Frey, is a method of evaluating mechanical allodynia in mice and rats. 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). Anim. 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). Behav. doi: 10.1152/physrev.00025.2008, Santos-Nogueira, E., Redondo Castro, E., Mancuso, R., and Navarro, X. Joint Bone Spine 72, 359371. The HomeCageScan has been validated in mouse models of post-surgical pain following vasectomy and laparotomy (Roughan et al., 2009, 2016). doi: 10.1016/j.jpain.2013.06.008, Griffioen, M. A., Dernetz, V. H., Yang, G. S., Griffith, K. A., Dorsey, S. G., and Renn, C. L. (2015). Behavioural and electrophysiological characterisation of experimentally induced osteoarthritis and neuropathy in C57Bl/6 mice. Water heated to 30C and applied the same way is usually used as a control (Carlton et al., 1994; Choi et al., 1994). (2011). Rodents are commonly used to study the pathophysiological mechanisms of pain as studies in humans may be difficult to perform and ethically limited. doi: 10.1097/fbp.0000000000000026, Banik, R. K., and Kabadi, R. A. Thus, pain is an experience that encompasses both sensory and emotional components; therefore the term pain is not interchangeable with nociception. Acetylsalicylic acid, paracetamol and morphine inhibit behavioral responses to intrathecally administered substance P or capsaicin. Their premise is based on the presumption that because we share similar biological processes, and because animals are whole, complex organisms, data obtained from an animal model can be extrapolated and . General adaptation syndrome was discovered accidentally by Selye whilst he was conducting experiments on rats at McGill University in Montreal, Canada. Brain Res. (2013). This continues until at least four readings are obtained after the first change of direction, and the sequence of outcomes ( for no response or + for response) is recorded (Figure 2A). Comparison of the antinociceptive action of and opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique. Thus, the term nociception is used to describe the peripheral neuronal response to noxious stimuli, which encompasses any stimuli, being mechanical, thermal, electrical or chemical, that have the potential to damage are damaging to tissue (Dubin and Patapoutian, 2010). To obtain reliable data, animals need to be habituated to the restraint method and experimental apparatus, which can become very time-intensive. The rat had historically been the preferred animal model for biomedical research due to genetic and physiological similarities to humans. However, the force required to trigger probe heating is low (~1 g), adjustable, and the surface of the heating probe is rather large compared to the punctate von Frey filaments. A small metal probe is applied to the hind paw, and heating is triggered by rotation of the handheld device until the mouse withdraws the paw. (2003). The assay is also capable of detecting side effects of analgesics, such as drowsiness, although it may be difficult to distinguish whether decreased burrowing arises from lack of efficacy or adverse effects unless additional behavioral tests or full dose-response curves are performed (Andrews et al., 2012). 30, 49334942. Quantitative sensory testing in the german research network on neuropathic pain (DFNS): standardized protocol and reference values. The most common case of bias is a result of non-response. Neurosci. 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. The increasing-temperature hot-plate test: an improved test of nociception in mice and rats. But the missing genes signal a problem for using gene editing to de-extinct species. Behav. It is now possible to more easily manipulate the rat genome to produce specific gene knockouts and knockins and apply results to our understanding of human genetic disorders. Animals 6:47. doi: 10.3390/ani6080047. A Biol. It remains to be determined whether pain behavior outcomes obtained using gait and weight-bearing analysis will translate more (or less) readily to the clinic compared to stimulus-evoked methods. While species such as saccharomyces cerevisiae, fruit flies, and zebrafish have been used for the study of cancer, organ development, recombination or large scale mutations, the rat model offers insights into human disease that the study of other species will not allow. (B) Electronic von Frey (MouseMet, TopCat Metrology). Analgesic effects of clinically used compounds in novel mouse models of polyneuropathy induced by oxaliplatin and cisplatin. Temperature 3, 7791. 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). Rodent models of cerebral palsy have been studied for almost forty years to fill the gaps in our knowledge, hopefully pointing the way to future treatments. Temperature preference assays are typically relatively fast and require little rodent handling or restraint (Morgan et al., 2012). Lancet Neurol. Diabetes Res. The same is likely to be true of other rodent species, many of . Neurosci. Burrowing in rodents: a sensitive method for detecting behavioral dysfunction. 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). Allowing rodents to have several trial runs prior to the actual experiment can increase burrowing behaviors and reduce variability (Deacon, 2006b). (C) Weight bearing (incapacitance test). Rev. Lancet 353, 19591964. However, irrespective of the method used, the endpoint is paw withdrawal to a stimulus that is not normally aversive, and thus both methods can measure mechanical allodynia. Rodents are allowed to freely move between a reference plate (neutral temperature) and test plate. 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. The force is increased by rotation of the handheld device until paw withdrawal occurs. J. It is plausible that differences in behavior may relate to the type of sensory fiber activated. Both the mouse and rat grimace scale are limited by the need for extensive training of the observer and a degree of subjectivity, which could lead to variability. Cybersex and pornography addiction. Biol. 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). Toxicol. Burns 43, 304309. 95% of all animals used in research are rats because their genetic, biological and behavioral characteristics are so similar to that of humans. Particular mention should also go to timely publication of data, be it positive or negative results, in order to reduce experimental duplication and unnecessary use of animals. Rotation of the handle of the hand-held device initiates heating from room temperature to 60C at a rate of 2.5C/s, which is terminated automatically by paw withdrawal, removal of the probe from the paw by the operator, or on reaching a predetermined cut-out (usually 60C; Figure 3D). 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. Several commercial automated gait analysis systems have been developed, including the CatWalk XT (Noldus) and GaitLab (ViewPoint Behavior Technology), which use internally reflected light to illuminate paw prints as an animal walks across an elevated glass floor (Figure 6D), and DigiGait (Mouse Specifics Inc.) and GaitScan/TreadScan (CleverSys), which use video recordings and automated software to analyze paw prints of animals walking on a transparent belt treadmill or clear floor walkway (Berryman et al., 2009; Parvathy and Masocha, 2013; Adams et al., 2016). Nat. Pain 123, 231243. In addition, while a pain face is apparent in some models of moderate duration (including acetic-acid induced writhing, the second phase of the formalin test, post-surgical pain and after intraplantar injection of mustard oil or zymosan) short nociceptive stimuli (including tail clip and tail-flick tests), and models of long-lasting neuropathic pain (including the chronic constriction injury and spared nerve injury model), are not associated with altered facial features (Langford et al., 2010). 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). doi: 10.1371/journal.pone.0098856, Huang, S. M., Li, X., Yu, Y., Wang, J., and Caterina, M. J. 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. 4:165. doi: 10.3389/fnbeh.2010.00165, Kayser, V., and Christensen, D. (2000). To evaluate thermal sensitivity, the time taken to settle in a temperature zone, as well as the temperature of the chosen zone, can be compared to control animals. Physiol. The burrowing assay has been validated for models of post-surgical pain in mice and in models of peripheral nerve injury, osteoarthritis and inflammation induced by CFA in rats (Jirkof et al., 2010; Andrews et al., 2012; Bryden et al., 2015). 27, 1368013690. J. Chem. (2011). 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. The clinical picture of neuropathic pain. 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. Influence of skin temperature on heat pain threshold in humans. 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). 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. Pain 150, 340350. Nurs. They helped shape the ideas of operant conditioning in behaviorism. Any long-term research involves mice and rats because of this unique aspect to the research. Research scientists worldwide agree that the use of rat models for disease research and experimentation has become more relevant in the past few years. Pain 154, 17491757. Pain Med. 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. Exceptionally adaptable, these rodents now inhabit almost all environments on Earth, especially near human settlements where they are often seen as pests. 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 . Pain 96, 129140. 14 Articles, This article is part of the Research Topic, Creative Commons Attribution License (CC BY). An estimated 71% of all NIH grant applications from 2008 to 2015 mentioned the keywords mus musculus, mouse, or mice. The sequenced genome will also unveil new targets for drug intervention.
Revere Police Log,
Sea Of Thieves Plunder Valley Riddle Colossal Bird Shrine,
Michelin Star Restaurants Oregon,
Articles OTHER