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Comparison of Thermal and Mechanical Pain Testing Modalities in Sprague Dawley and Fischer 344 Rats (Rattus norvegicus). Sprague Dawley 大鼠和 Fischer 344 大鼠(Rattus norvegicus)热痛和机械痛测试模式的比较。
Pub Date : 2024-03-08 DOI: 10.30802/AALAS-JAALAS-23-000094
James F McNew, Daniel J Davis, Kristin N Grimsrud, Elizabeth C Bryda

While rodents are used extensively for studying pain, there is a lack of reported direct comparisons of thermal and mechanical pain testing methods in rats of different genetic backgrounds. Understanding the range of interindividual variability of withdrawal thresholds and thermal latencies based on these testing methods and/or genetic background is important for appropriate experimental design. Testing was performed in two common rat genetic backgrounds: outbred Sprague-Dawley (SD) and inbred Fischer 344 (F344). Male and female, 10- to 14-wk-old F344 and SD rats were used to assess withdrawal thresholds in 3 different modalities: the Randall-Selitto test (RST), Hargreaves test (HT), and tail flick test (TFT). The RST was performed by using an operator-controlled handheld instrument to generate a noxious pressure stimulus to the left hind paw. The HT and the TFT used an electronically controlled light source to deliver a noxious thermal stimulus to the left hind paw or tail tip, respectively. Rats of each sex and genetic background underwent one type of test on day 0 and day 7. Withdrawal thresholds and thermal latencies were compared among tests. No significant differences were observed. Our findings can serve as a guide for researchers considering these nociceptive tests for their experiments.

虽然啮齿类动物被广泛用于疼痛研究,但缺乏对不同遗传背景大鼠的热痛和机械痛测试方法进行直接比较的报道。了解基于这些测试方法和/或遗传背景的戒断阈值和热潜伏期的个体间变异范围对于适当的实验设计非常重要。测试在两种常见的大鼠遗传背景中进行:近交种 Sprague-Dawley (SD) 和近交种 Fischer 344 (F344)。雄性和雌性、10 到 14 周大的 F344 和 SD 大鼠被用来评估三种不同模式的戒断阈值:兰德尔-塞利托试验(RST)、哈格里夫斯试验(HT)和弹尾试验(TFT)。RST 是使用操作员控制的手持仪器对左后爪产生有害的压力刺激。HT和TFT使用电子控制光源,分别对左后爪或尾尖产生有害的热刺激。每种性别和遗传背景的大鼠分别在第0天和第7天接受一种类型的测试。比较了不同测试的戒断阈值和热潜伏期。没有观察到明显的差异。我们的研究结果可作为研究人员考虑在实验中使用这些痛觉测试的指南。
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引用次数: 0
Differences in Fluid, Electrolyte, and Energy Balance in C57BL/6J Mice (Mus musculus) in Metabolic Caging at Thermoneutral or Standard Room Temperatures. C57BL/6J小鼠(Mus musculus)在中温或标准室温下代谢笼养过程中的体液、电解质和能量平衡差异。
Pub Date : 2024-03-01 Epub Date: 2024-01-08 DOI: 10.30802/AALAS-JAALAS-23-000091
Samuel Br Lawton, Connie C Grobe, John J Reho, Hershel Raff, Joseph D Thulin, Eric S Jensen, Colin Ml Burnett, Jeffrey L Segar, Justin L Grobe

The Guide for the Care and Use of Laboratory Animals recommends mice be pair or group housed and provided with nesting materials. These provisions support social interactions and are also critical for thermoregulatory behaviors such as huddling and burrowing. However, studies of fluid and electrolyte balance and digestive function may involve use of metabolic caging (MC) systems in which mice are housed individually on wire-mesh floors that permit quantitative collection of urine and feces. MC housing prevents mice from performing their typical huddling and burrowing behaviors. Housing in MC can cause weight loss and behavioral changes in rodents. Here, we tested the hypothesis that MC housing of mice at standard room temperature (SRT, 22 to 23 °C) exposes them to cold stress, which causes metabolic changes in the mice as compared with standard housing. We hypothesized that performing MC studies at a thermoneutral temperature (TNT, 30 °C) would minimize these changes. Fluid, electrolyte, and energy balance and body composition were assessed in male and female C57BL/6J mice housed at SRT or TNT in MC, static microisolation cages, or a multiplexed metabolic phenotyping system designed to mimic static microisolation cages (Promethion, Sable Systems International). In brief, as compared with MC housing at SRT, MC housing at TNT was associated with lower food intake and energy expenditure, absence of weight loss, and lower urine and fecal corticosterone levels. These results indicate that housing in MC at SRT causes cold stress that can be mitigated if MC studies are performed at TNT.

实验动物饲养和使用指南》建议小鼠应成对或成群饲养,并提供筑巢材料。这些规定有助于小鼠的社会交往,对小鼠的体温调节行为(如蜷缩和钻洞)也至关重要。不过,对体液和电解质平衡以及消化功能的研究可能需要使用代谢笼(MC)系统,在该系统中,小鼠被单独饲养在铁丝网地板上,以便定量收集尿液和粪便。代谢笼饲养系统使小鼠无法进行典型的蜷缩和钻洞行为。MC饲养会导致啮齿动物体重减轻和行为改变。在此,我们测试了一个假设,即在标准室温(SRT,22 至 23 °C)下饲养 MC 会使小鼠面临冷应激,与标准饲养相比,冷应激会导致小鼠的新陈代谢发生变化。我们假设在恒温(TNT,30 °C)下进行 MC 研究将最大程度地减少这些变化。我们对在 SRT 或 TNT 温度下饲养的雌雄 C57BL/6J 小鼠的体液、电解质和能量平衡以及身体成分进行了评估,这些小鼠分别饲养在 MC、静态微隔离笼或模拟静态微隔离笼设计的多重代谢表型系统(Promethion,Sable Systems International)中。简而言之,与SRT的MC饲养相比,TNT的MC饲养与较低的食物摄入量和能量消耗、无体重下降以及较低的尿液和粪便皮质酮水平有关。这些结果表明,在SRT饲养MC会造成寒冷应激,如果在TNT进行MC研究,则可减轻这种应激。
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引用次数: 0
Letter to the Editor Regarding "Assessing Methods for Replacement of Soiled Bedding Sentinels in Cage-level Exhaust IVC Racks" by Eichner and Smith. 致编辑的信,内容涉及 Eichner 和 Smith 撰写的 "评估更换笼级排气式 IVC 架中脏污垫料哨兵的方法"。
Pub Date : 2024-03-01 Epub Date: 2024-01-30 DOI: 10.30802/AALAS-JAALAS-23-000111
Chris Manuel, Kerith Luchins, Norman C Peterson, Aurore Dodelet-Devillers, Christina Pettan-Brewer, Lise Phaneuf, Joseph P Garner, Megan Lafollette
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引用次数: 0
Effects of Home Cage Tunnels on Within-cage Behaviors of Mice with Cranial Implants. 家笼隧道对颅骨植入小鼠笼内行为的影响
Pub Date : 2024-03-01 Epub Date: 2024-01-29 DOI: 10.30802/AALAS-JAALAS-22-000087
Marissa G Castronovo, Daniel W Wesson

Keeping tunnels in the home cages of mice used in research appears to both reduce handling-related stress and provide environmental enrichment. However, for mice that have surgical implants that extend beyond their body, having tunnels in the home cages could engender concerns for their welfare, including the possibility of them becoming stuck in the tunnel. The goal of this study was to determine how mice with different sizes of cranial implants interacted with a tunnel in their home cage. We used male and female mice with a C57BL/6J background in this study. The mice underwent a either a craniotomy in which they received either no implant (sham), an indwelling cannula used for drug delivery, or a ferrule-type implant. The number of mouse interactions with tunnels was recorded over a 30-min period while the mouse was in its home cage with its tunnel. We found that sham mice interacted significantly more with the tunnels than did mice with either cannulae or ferrule implants. On average sham mice interacted more with the tunnel by walking through or over it whereas mice with either type of implant rarely even touched the tunnel with their heads. Our results indicate that mice with implants do not enter in the tunnels, and thus the tunnel reduces accessible cage-space rather than providing enrichment benefits. These results raise the question of whether tunnels should be routinely available for mice with cranial implants.

在研究用小鼠的家笼内设置隧道似乎既能减少与操作相关的压力,又能提供丰富的环境。然而,对于手术植入物超出身体的小鼠来说,在家养笼中放置隧道可能会引起对其福利的担忧,包括它们可能会被隧道卡住。本研究的目的是确定颅骨植入物大小不同的小鼠如何与家笼内的隧道相互作用。我们在这项研究中使用了 C57BL.6J 背景的雄性和雌性小鼠。这些小鼠要么接受了开颅手术,要么没有接受植入物(假),要么接受了用于给药的留置插管,要么接受了卡套式植入物。我们记录了小鼠在30分钟的时间内与隧道互动的次数,当时小鼠正在笼子里与隧道互动。我们发现,假小鼠与隧道的互动次数明显多于植入套管或卡环的小鼠。平均而言,假小鼠与隧道的互动更多是通过走过或越过隧道,而植入任何一种植入物的小鼠甚至很少用头接触隧道。我们的研究结果表明,植入植入物的小鼠不会进入隧道,因此隧道减少了可进入的笼子空间,而不是提供了丰富的益处。这些结果提出了一个问题:是否应该为植入颅骨的小鼠提供常规隧道?
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引用次数: 0
Light: An Extrinsic Factor Influencing Animal-based Research. 光:影响动物研究的外在因素
Pub Date : 2024-03-01 Epub Date: 2024-01-11 DOI: 10.30802/AALAS-JAALAS-23-000089
Robert T Dauchy, John P Hanifin, George C Brainard, David E Blask

Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors-rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones. The rods and cones of the visual system, along with the ipRGCs of the nonvisual system, are species distinct in terms of opsins and opsin concentrations and interact with one another to provide vision and regulate circadian rhythms of neurohormonal and neurobehavioral responses to light. Here, we review a brief history of lighting technologies, the nature of light and circadian rhythms, our present understanding of mammalian photoreception, and current industry practices and standards. We also consider the implications of light for vivarium measurement, production, and technological application and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and well-being and, ultimately, improving scientific outcomes.

光是一种外在于动物自身的环境因素,它对包括研究动物在内的所有动物的昼夜节律、神经激素、新陈代谢和神经行为系统的调节产生深远影响。光的这些广泛的生物效应是由不同的光感受器介导的--构成传统视觉系统的视杆细胞和视锥细胞,以及与视杆细胞和视锥细胞相互作用的非视觉系统中含有黑视蛋白的固有光敏视网膜神经节细胞(ipRGCs)。视觉系统中的视杆细胞和视锥细胞,以及非视觉系统中的ipRGCs,在视蛋白和视蛋白浓度方面是不同的物种,它们相互影响,提供视觉,并调节神经激素和神经行为对光的反应的昼夜节律。在此,我们将简要回顾照明技术的历史、光和昼夜节律的本质、我们目前对哺乳动物光感的理解,以及当前的行业实践和标准。我们还考虑了光对活体测量、生产和技术应用的影响,并提供了有关人工照明的简单建议,供监管机构、照明制造商、设计师、工程师、研究人员和研究动物护理人员使用,以确保优化动物健康和福祉的最佳实践,并最终改善科学成果。
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引用次数: 0
Erratum: Evaluation and Refinement of a Spot-change-only Cage Management System for Mice. 勘误:小鼠仅定点换笼管理系统的评估与改进
Pub Date : 2024-03-01 DOI: 10.30802/AALAS-JAALAS-24-000012
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引用次数: 0
Evaluation of Vibration as an Extrinsic Variable in In Vivo Research. 将振动作为体内研究的外部变量进行评估。
Pub Date : 2024-03-01 Epub Date: 2024-01-05 DOI: 10.30802/AALAS-JAALAS-23-000050
Randall P Reynolds, John N Norton

Vibration is inherent in research animal facilities due to the mechanical systems and practices required for animal care and use. Ample evidence indicates that vibration can change behavior and physiology in multiple species, potentially altering the results of research studies. Although one cannot eliminate environmental vibration, its control is important in research animal environments to decrease the possibility of introducing a research variable due to vibration effects. To assess the potential for a vibration source to alter experimental results and variability, one must understand the principles of vibration, its likely sources, and control methods. The literature regarding the effects of vibration, as it applies in a practical sense, can be challenging to interpret because the vibration frequencies tested to date have often not been within or near the most sensitive ranges of the species being tested. Some previous studies have used unrealistic vibration magnitudes and provided insufficient detail to duplicate or build upon conclusions. Standardization is essential for research examining the effects of vibration on animals to validate knowledge of this extrinsic variable in animal research and identify ways to mitigate the variable in research facilities.

由于动物护理和使用所需的机械系统和操作方法,振动是研究动物设施中固有的现象。大量证据表明,振动会改变多个物种的行为和生理,从而可能改变研究结果。虽然我们无法消除环境振动,但在研究动物的环境中控制振动非常重要,这样可以减少因振动影响而引入研究变量的可能性。要评估振动源改变实验结果和变异性的可能性,必须了解振动原理、可能的振动源和控制方法。由于迄今为止测试的振动频率往往不在或接近被测物种的最敏感范围内,因此有关振动影响的文献在实际应用中很难解释。以前的一些研究使用了不切实际的振动幅度,并且没有提供足够的细节来重复或建立结论。标准化对于研究振动对动物的影响至关重要,它可以验证动物研究中这一外在变量的知识,并确定在研究设施中减轻该变量的方法。
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引用次数: 0
Extrinsic Environmental Variables: The Umwelt of Research Animals and the Implications for the 3Rs and Study Reproducibility. 外在环境变量:研究动物的生存环境及其对 3Rs 和研究可重复性的影响。
Pub Date : 2024-03-01 DOI: 10.30802/AALAS-JAALAS-24-000024
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引用次数: 0
A Comparison of Three Anesthetic Drug Combinations for Use in Inducing Surgical Anesthesia in Female Guinea Pigs (Cavia porcellus). 比较用于诱导雌性豚鼠(Cavia porcellus)手术麻醉的三种麻醉药物组合。
Pub Date : 2024-03-01 Epub Date: 2024-01-05 DOI: 10.30802/AALAS-JAALAS-23-000064
Janelle A Avelino, Courtney A Walsh, Keely Nicole Wharton, Dinesh Ekanayake, Dil Ekanayake-Alper

Guinea pigs are often used in translational research, but providing them with safe and effective anesthesia is a challenge. Common methods like inhalant anesthesia and injectable ketamine/xylazine induce surgical anesthesia but can negatively affect cardiovascular, respiratory, and thermoregulatory systems and complicate the interpretation of research outcomes. Several alternative anesthetic regimens have been investigated, but none have consistently achieved a surgical plane of anesthesia. Therefore, identifying an anesthetic regimen that achieves a stable state of the surgical plane of anesthesia while preserving cardiorespiratory function would be a valuable contribution. To address this issue, we compared the efficacy of 3 anesthetic combinations in female Dunkin-Hartley guinea pigs: 1) alfaxalone, dexmedetomidine, and fentanyl (ADF); 2) alfaxalone, midazolam, and fentanyl (AMF); and 3) alfaxalone, midazolam, fentanyl, and isoflurane (AMFIso). We monitored anesthetic depth, heart rate, oxygenation, respiratory rate, respiratory effort, blood pressure, and body temperature every 15 min from injection to recovery. We also recorded the time to loss of righting reflex, duration of anesthesia, and time to achieve a surgical plane. The results showed no statistically significant differences in induction and recovery times among the groups. In the AMFIso group, 100% of the animals achieved a surgical plane of anesthesia, whereas only 10% of the animals in the AMF group reached that level. None of the animals in ADF group reached a surgical plane of anesthesia. Respiratory rate was significantly lower in the AMFIso as compared with the ADF group (P < 0.001) but was not different between the AMF and ADF groups. Temperature was significantly lower in the AMFIso group as compared with both the ADF and AMF groups (P < 0.001). In conclusion, both combinations of solely injectable anesthetics assessed in this study can be used for short, nonpainful procedures without significant cardiorespiratory depression. However, for mildly to moderately painful surgical procedures, the addition of an inhalant anesthetic like isoflurane is necessary for female guinea pigs.

豚鼠经常被用于转化研究,但为它们提供安全有效的麻醉是一项挑战。吸入麻醉和注射氯胺酮/恶嗪等常用方法可诱导手术麻醉,但会对心血管、呼吸和体温调节系统产生负面影响,并使研究结果的解释复杂化。目前已对几种替代麻醉方案进行了研究,但没有一种方案能持续达到手术麻醉的效果。因此,确定一种既能实现稳定的手术麻醉平面状态,又能保护心肺功能的麻醉方案将是一项有价值的贡献。为了解决这个问题,我们比较了 3 种麻醉组合在雌性 Dunkin-Hartley 豚鼠身上的疗效:1)阿法沙隆、右美托咪定和芬太尼(ADF);2)阿法沙隆、咪达唑仑和芬太尼(AMF);3)阿法沙隆、咪达唑仑、芬太尼和异氟醚(AMFIso)。从注射到恢复,我们每 15 分钟监测一次麻醉深度、心率、血氧饱和度、呼吸频率、呼吸强度、血压和体温。我们还记录了右反射消失的时间、麻醉持续时间和达到手术平面的时间。结果显示,各组在诱导和恢复时间上没有明显的统计学差异。在AMFIso组中,100%的动物达到了手术麻醉平面,而在AMF组中只有10%的动物达到了这一水平。ADF组没有一只动物达到手术麻醉平面。AMFIso组的呼吸频率明显低于ADF组(P < 0.001),但AMF组与ADF组之间没有差异。与 ADF 组和 AMF 组相比,AMFIso 组的体温明显降低(P < 0.001)。总之,本研究中评估的两种纯注射麻醉剂组合均可用于短时间、无痛苦的手术,不会对心肺功能造成明显抑制。不过,对于轻度至中度疼痛的手术过程,雌性豚鼠有必要添加异氟醚等吸入性麻醉剂。
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引用次数: 0
Effect of Cage Change Frequency on Perinatal Mortality in C57BL/6J Mice. 换笼频率对 C57BL/6J 小鼠围产期死亡率的影响
Pub Date : 2024-03-01 Epub Date: 2023-12-07 DOI: 10.30802/AALAS-JAALAS-23-000055
Keely N Wharton, Courtney Walsh, Tory J Bauer-Pisani, Peter C Smith, Steven R Wilson

Perinatal mortality is a common problem in mouse breeding colonies. Few studies have examined the influence of environmental changes on mouse pup survival. In this study, monogamous breeding cages of C57BL/6J mice were set up and randomized into 3 cage change groups: 1) cage change at 8 d after parturition, 2) cage change at 3 d after parturition, or 3) cage change at 3 d after parturition with the addition of a polycarbonate hut in the cage. Pairs were bred to produce a minimum of 4 litters. Pup survival to weaning relative to experimental cage change date, and survival rates after cage change were evaluated. The results revealed no significant differences between experimental groups. The majority of pup loss occurred within the first 24 h after birth for those pups that were alive at birth. Overall, the postpartum day of cage change did not affect the perinatal survival of mouse pups.

围产期死亡是小鼠繁殖群中的一个常见问题。很少有研究探讨环境变化对小鼠幼仔存活率的影响。在本研究中,我们设置了一夫一妻制的 C57BL/6J 小鼠繁殖笼,并将其随机分为 3 个换笼组:1)产后 8 d 换笼;2)产后 3 d 换笼;或 3)产后 3 d 换笼,并在笼中添加聚碳酸酯小屋。配对繁殖至少产下 4 胎。评估了与换笼日期相关的幼仔断奶存活率和换笼后的存活率。结果显示,实验组之间没有明显差异。对于出生时存活的幼崽来说,大部分损失发生在出生后的 24 小时内。总体而言,产后换笼日对幼鼠围产期存活率没有影响。
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引用次数: 0
期刊
Journal of the American Association for Laboratory Animal Science : JAALAS
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