Name: back mechanical sensitivity assessment in the rat for mechanistic investigation of chronic back pain
Uploaded: 2022-08-30T13:00:00
Description: Watch this Scientific Journal Video about Back Mechanical Sensitivity Assessment in the Rat for Mechanistic Investigation of Chronic Back Pain at JoVE.com

这项工作得到了魁北克脊椎基金会和加拿大自然科学与工程研究理事会（MP：grant #06659）的资助。香港的贡献得到了魁北克三河大学（PAIR计划）的支持。BP的贡献得到了魁北克健康研究基金会（FRQS）和魁北克脊椎基金会的支持。TP的贡献得到了加拿大自然科学和工程研究理事会的支持。NE和EK的贡献得到了魁北克脊椎基金会的支持。MP 的贡献得到了 FRQS 的支持。

该实验方案得到了魁北克三河大学动物护理委员会的批准，并符合加拿大动物护理理事会的指导方针和国际疼痛研究协会（IASP）的研究和伦理问题委员会的指导方针。本研究使用了六只雄性Wistar大鼠（体重：320-450克;年龄：18-22周）。这些动物是从商业来源获得的（见 材料表）。这些大鼠的数据来自先前研究30的较大样本。
1. 实验准备</stron...

<ol>
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关键步骤 BMS测试是一种评估大鼠背部机械敏感性的简单方法，无论是在一个时间点还是在几天或几周内重复，当预期会发生变化（疼痛模型）或在药物或非药物干预后。该方法的关键问题包括测试笼，其尺寸必须确保大鼠舒适但不会移动太多。动物的背部必须通过网状天花板保持可接近，以实现可重复的机械刺激。为了限制阈值评估的变异性，必须剃掉被研究的背部区域，以便将?...

腰痛（LBP）是全球残疾的主要原因，具有严重的个人，经济和社会后果1，2，3，4。每年，约有37%的人口受到LBP5的影响。腰痛通常在几周内消退，但在 24%-33% 的个体中复发，在 5%-10% 的病例中变为慢性2.为了了解LBP的机制和影响以及不同治疗干预的效果，已经使用了几种LBP动物模型，模拟临床条件或LBP6的某些成分。这些小鼠和大鼠模型可分为以下一个或多个类别：（1）椎间盘性LBP7，8，，（2）根性LBP 8，9，10，11，（3）小关节骨关节炎12和（4）肌肉诱导的LBP13，14.由于疼痛不能直接在非人类物种中测量，因此已经开发了许多测试来量化这些模型中的类似疼痛的行为8。这些测试评估由有害刺激（机械力15，16，17，热刺激18，19，20，21，22，23，24，25）或自发产生的行为26，27，28，29。
使用机械刺激的方法包括冯弗雷检验15，16和兰德尔-塞利托检验17。使用热刺激的方法包括尾部轻弹测试18、热板测试19、哈格里夫斯测试20和热探针测试21。使用冷刺激的方法包括冷板试验22、丙酮蒸发试验23和冷足底试验24。自发行为的方法包括鬼脸秤26，挖洞27，负重和步态分析28，以及自动行为分析29。尽管有这么多可用的测试，但没有一个是专门为背痛模型设计的。
这项研究的目的是制定一个简单易用的测试来评估大鼠背部的机械敏感性。该技术主要基于应用于后爪足底表面的冯弗雷测试15，16。冯弗雷测试的基本原理是使用一系列单丝到感兴趣的区域，提供恒定的预定力。如果大鼠表现出伤害性行为，则反应被认为是积极的。然后可以根据引起响应的细丝计算机械阈值。在本研究中，提供了一种基于冯弗雷测试的简单易行的方法来确定大鼠背部的机械敏感性。

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	<tbody>
		<tr>
			<td>Aerrane (isoflurane, USP) - Veterinary Use Only</td>
			<td>Baxter</td>
			<td>NDC 10019-773-60</td>
			<td>Inhalation Anaesthetic ; DIN 02225875, for inducing anasthesia</td>
		</tr>
		<tr>
			<td>Complete Freund Adjuvant (CFA)</td>
			<td>Fisher Scientific</td>
			<td>#77140</td>
			<td>Water-in-oil emulsion of Complete Freund Adjuvant (CFA) with killed cells of Mycobacterium butyricum.</td>
		</tr>
		<tr>
			<td>Male Wistar Rats</td>
			<td>Charles River Laboratories</td>
			<td></td>
			<td>body weight: 320&#8211;450 g; age: 18-22 weeks.</td>
		</tr>
		<tr>
			<td>Penlon Sigma Delta Vaporizer</td>
			<td>Penlon</td>
			<td>990-VI5K-SVEEK</td>
			<td>Penlon Sigma Delta Vaporizer used for anasthesia</td>
		</tr>
		<tr>
			<td>Sharpie Permanent Marker</td>
			<td>Sharpie</td>
			<td>BC23636</td>
			<td>Permanent Marker, Fine Point, Black</td>
		</tr>
		<tr>
			<td>Test cage</td>
			<td>Custom-made</td>
			<td></td>
			<td>Width: 20 cm;&#160; Length: 50 cm; Height from the bottom to the top: 40 cm; Height from the bottom mesh to the top of the cage: 7 cm; Wall thickness: 5 mm; Mesh: 1 mm wire with an 8 mm inter-wire distance&#160;&#160;&#160;</td>
		</tr>
		<tr>
			<td>Von Frey Filaments</td>
			<td>Aesthesio, Precise Tactile Sensory Evaluator</td>
			<td>514000-20C</td>
			<td>Filaments from 0.07 g to 26 g</td>
		</tr>
		<tr>
			<td>Wahl Professional Animal, ARCO Cordless Pet Clipper, Trimmer Grooming&#160;</td>
			<td>Wahl</td>
			<td>Kit #8786-1201</td>
			<td>Animal hair trimmer, for shaving purposes, zero blade&#160;</td>
		</tr>
	</tbody>
</table>

back mechanical sensitivity assessment in the rat for mechanistic investigation of chronic back pain

腰痛是全世界残疾的主要原因，具有严重的个人、经济和社会后果。为了开发新的治疗方法，需要动物模型从转化角度检查新疗法的机制和有效性。在当前的研究中使用了几种啮齿动物的背痛模型。然而，令人惊讶的是，没有标准化的行为测试被验证来评估背痛模型中的机械敏感性。这对于确认推定背痛的动物对伤害性刺激存在局部超敏反应以及在旨在缓解背痛的干预措施期间监测敏感性至关重要。这项研究的目的是制定一个简单易用的测试来评估大鼠背部的机械敏感性。专门为这种方法制造了一个测试笼;长 x 宽 x 高：50 x 20 x 7 厘米，顶部有不锈钢网。该测试笼允许在背部施加机械刺激。为了进行测试，在感兴趣的区域剃掉动物的背部，并根据需要标记测试区域以在不同日期重复测试。机械阈值是通过将冯弗雷细丝应用于椎旁肌肉来确定的，使用前面描述的上下方法。积极的反应包括（1）肌肉抽搐，（2）拱起（背部伸展），（3）颈部旋转（4）抓挠或舔背部，以及（5）逃跑。该行为测试（背部机械敏感性（BMS）测试）可用于啮齿动物背痛模型的机制研究，以开发预防和管理背痛的治疗干预措施。

该方法用于先前的研究，其中提供了完整的数据和统计数据，以比较CFA和对照大鼠之间的机械敏感性30。来自先前研究中包含的六只大鼠的代表性个体数据（左右阈值的平均值）如图 3 和 表1所示。在基线时，两组之间的机械敏感性相似。在腰肌肌内注射CFA导致CFA注射后机械敏感性从7天显着增加到28天。相比之下，对照（CTL）大鼠没有表现出这?...

Watch this Scientific Journal Video about Back Mechanical Sensitivity Assessment in the Rat for Mechanistic Investigation of Chronic Back Pain at JoVE.com

Back Mechanical Sensitivity Assessment in the Rat for Mechanistic Investigation of Chronic Back Pain

为了开发预防和管理背痛的新型治疗干预措施，需要动物模型从转化角度检查这些疗法的机制和有效性。本协议描述了BMS测试，这是一种评估大鼠背部机械敏感性的标准化方法。

大鼠背部机械敏感性评估用于慢性背痛的机制研究

Low back pain is the leading cause of disability worldwide, with dramatic personal, economic, and social consequences. To develop novel therapeutics, ...

该协议可用于测试背部的机械灵敏度。对于慢性背痛大鼠模型中的纵向设计特别有趣，其目标是检查干预措施的有效性，以降低对有害刺激的背部敏感性。该方法简单易用，并且在训练有素的实验人员中产生可重复的结果。它主要基于冯弗雷测试，该测试通常用于评估后爪的机械敏感性。至于任何其他行为测试，实验者应该练习标准化细丝的应用，直到机械刺激产生的行为很容易与其他行为区分开来。测试很简单，否则，使用它应该没有大的困难。演示该程序的将是我实验室的博士生Nasim Eskandari。为了引起大鼠的慢性背痛，将完全弗氏佐剂或CFA肌内注射到背部肌肉中。使用 27 号针头，单侧或双侧将 150 微升即用型油包油中 CFA 乳液注射到椎旁肌肉中。将针头固定到位至少三分钟。接下来，通过将两个连续的室安装在四个 33 厘米长的有机玻璃腿上，为两只动物制造一个测试笼，包括每只动物的一个腔室。使用透明有机玻璃作为房间的墙壁，并使用黑色有机玻璃分隔房间以防止动物看到彼此。然后使用由一毫米线制成的不锈钢网制作测试笼的地板和天花板，线间距离为八毫米。在第一次测试之前，每天让大鼠熟悉测试笼30分钟，连续五到七天。在异氟醚麻醉下的俯卧位，使用动物毛发修剪器在大约 10 个椎体水平上剃掉感兴趣区域的后毛。对于重复措施，每三天剃一次背毛，无需行为评估，以确保刺激始终直接施加在皮肤上。用永久性记号笔在皮肤上画一个标记，以确保在不同日期重复测试时始终将细丝应用于同一区域。在测试当天，在测试前将大鼠放入测试笼中 15 到 30 分钟，直到大鼠平静下来。然后垂直于背面涂抹冯弗雷细丝，始终从两克长丝开始并使用向上/向下方法。当大鼠清醒时，用四只爪子站立并且不动时，每15至30秒将细丝双向施加到距脊柱10毫米的感兴趣区域两秒钟。如果在施加灯丝时没有观察到响应，请以更大的力施加系列中的下一根灯丝。如果观察到积极的反应，例如拱背、舔舐、肌肉抽搐、远离细丝或旋转，请使用系列中力较小的下一根细丝。继续该过程，直到在第一次行为改变后获得四个读数。在这项研究中，研究了CFA和对照大鼠之间的背部机械敏感性。在基线时，两组之间的机械敏感性相似。在腰肌中肌内注射CFA导致机械敏感性从7天显着增加到28天。相比之下，对照大鼠没有表现出任何显着的变化。此外，组织学检查证实注射CFA的肌肉中存在慢性炎症变化，白细胞浸润清晰。肌内注射生理盐水后来自受控大鼠的健康背部肌肉作为参考。除了背部肌肉外，还通过标准冯弗雷测试在后爪观察到机械超敏反应。确保灯丝始终以垂直于背部的相同方式施加非常重要，并且在应用时动物不会移动。实验者还应该有信心区分现代运动的行为反应。

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Research

JoVE Journal

Behavior

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

We present an operant system for the detection of pain in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) assesses pain behaviors in a more clinically relevant way by not relying on reflex-based measures of nociception. Food fasted, hairless (or shaved) rodents are placed into a Plexiglas chamber which has two Peltier-based thermodes that can be programmed to any temperature between 7 &deg;C and 60 &deg;C. The rodent is trained to make contact with these in order to access a reward bottle. During a session, a number of behavioral pain outcomes are automatically recorded and saved. These measures include the number of reward bottle activations (licks) and facial contact stimuli (face contacts), but custom measures like the lick/face ratio (total number of licks per session/total number of contacts) can also be created. The stimulus temperature can be set to a single temperature or multiple temperatures within a session. The OPAD is a high-throughput, easy to use operant assay which will lead to better translation of pain research in the future as it includes cortical input instead of relying on spinal reflex-based nociceptive assays.

Use of the Operant Orofacial Pain Assessment Device OPAD to Measure Changes in Nociceptive Behavior

We present a user-friendly, high-throughput operant system for the evaluation of pain behaviors in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) can assess pain through a reward/conflict paradigm thus providing a more humane way of testing. This protocol will yield more clinically relevant and translational data from rodents.

使用操作性口面疼痛评估设备（OPAD）测量伤害行为的变化

We present an operant  system for the detection of pain in awake, conscious rodents. The Orofacial  Pain Assessment Device (OPAD) assesses pain behaviors ...

科研

行为学

A Protocol of Manual Tests to Measure Sensation and Pain in Humans

Numerous qualitative and quantitative techniques can be used to test sensory nerves and pain in both research and clinical settings. The current study demonstrates a quantitative sensory testing protocol using techniques to measure tactile sensation and pain threshold for pressure and heat using portable and easily accessed equipment. These techniques and equipment are ideal for new laboratories and clinics where cost is a concern or a limiting factor. We demonstrate measurement techniques for the following: cutaneous mechanical sensitivity on the arms and legs (von-Frey filaments), radiant and contact heat sensitivity (with both threshold and qualitative assessments using the Visual Analog Scale (VAS)), and mechanical pressure sensitivity (algometer, with both threshold and the VAS). The techniques and equipment described and demonstrated here can be easily purchased, stored, and transported by most clinics and research laboratories around the world. A limitation of this approach is a lack of automation or computer control. Thus, these processes can be more labor intensive in terms of personnel training and data recording than the more sophisticated equipment. We provide a set of reliability data for the demonstrated techniques. From our description, a new laboratory should be able to set up and run these tests and to develop their own internal reliability data.

The goal of this procedure is to demonstrate a battery of quantitative techniques for sensory and pain measurement in humans. The equipment and techniques described are commonly found in pain clinics or are easy to obtain.

手动测试的协议来衡量感觉和疼痛人类

Numerous qualitative and quantitative techniques can be used to test sensory nerves and pain in both research and clinical settings. The current study ...

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is fairly simple and can be completed over 3 days: habituation day, training day, and testing day. During training, the mouse is allowed to explore 2 identical objects. On test day, one of the training objects is replaced with a novel object. Because mice have an innate preference for novelty, if the mouse recognizes the familiar object, it will spend most of its time at the novel object. Due to this innate preference, there is no need for positive or negative reinforcement or long training schedules. Additionally, the ORT can also be modified for numerous applications. The retention interval can be shortened to examine short-term memory, or lengthened to probe long-term memory. Pharmacological intervention can be used at various times prior to training, after training, or prior to recall to investigate different phases of learning (i.e., acquisition, early or late consolidation, or recall). Overall, the ORT is a relatively low-stress, efficient test for memory in mice, and is appropriate for the detection of neuropsychological changes following pharmacological, biological, or genetic manipulations.

The object recognition test (ORT) is a simple and efficient assay for evaluating learning and memory in mice. The methodology is described below.

小鼠学习记忆研究的新对象识别实验

The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is ...

Treating Low Back Pain in Failed Back Surgery Patients with Multicolumn-lead Spinal Cord Stimulation

Failed back surgery syndrome (FBSS) refers to persistent, chronic pain following spinal surgery. Spinal cord stimulation with dorsal epidural leads can be used to treat back and leg pain in FBSS patients. This paper presents a detailed protocol for using spinal cord stimulation with surgical leads in FBSS patients. In our department, with the patient under general anesthesia, we place the lead in the epidural space by means of a small laminectomy at the 10th thoracic level. Placement of the lead is followed by a 1 month trial period with an externalized lead. If pain relief is greater than 50% at the end of this 1 month stimulation trial (required by Belgian reimbursement criteria), an internal pulse generator is then placed under the skin and connected to the lead in a second surgical procedure. We have demonstrated that using this technique in rigorously selected FBSS patients can significantly improve back pain, leg pain, patient activity, and quality of life for a sustained period of time.

This paper presents a method that uses spinal cord stimulation with a multicolumn lead to treat neuropathic low back pain in failed back surgery patients.

多列铅脊髓刺激术后腰痛的治疗

Failed back surgery syndrome (FBSS) refers to persistent, chronic pain following spinal surgery. Spinal cord stimulation with dorsal epidural leads can be ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

诱导小鼠快感缺失的不可预测慢性轻度应力协议

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Multi-Modal Signals for Analyzing Pain Responses to Thermal and Electrical Stimuli

The assessment of pain relies mostly on methods that require a person to communicate. However, for people with cognitive and verbal impairments, existing methods are not sufficient as they lack reliability and validity. To approach this problem, recent research focuses on an objective pain assessment facilitated by parameters of responses derived from physiology, and video and audio signals. To develop reliable automated pain recognition systems, efforts have been made in creating multimodal databases in order to analyze pain and detect valid pain patterns. While the results are promising, they only focus on discriminating pain or pain intensities versus no pain. In order to advance this, research should also consider the quality and duration of pain as they provide additional valuable information for more advanced pain management. To complement existing databases and the analysis of pain regarding quality and length, this paper proposes a psychophysiological experiment to elicit, measure, and collect valid pain reactions. Participants are subjected to painful stimuli that differ in intensity (low, medium, and high), duration (5 s / 1 min), and modality (heat / electric pain) while audio, video (e.g., facial expressions, body gestures, facial skin temperature), and physiological signals (e.g., electrocardiogram [ECG], skin conductance level [SCL], facial electromyography [EMG], and EMG of M. trapezius) are being recorded. The study consists of a calibration phase to determine a subject&#8217;s individual pain range (from low to intolerable pain) and a stimulation phase in which pain stimuli, depending on the calibrated range, are applied. The obtained data may allow refining, improving, and evaluating automated recognition systems in terms of an objective pain assessment. For further development of such systems and to investigate pain reactions in more detail, additional pain modalities such as pressure, chemical, or cold pain should be included in future studies. Recorded data of this study will be released as the &#8220;X-ITE Pain Database&#8221;.

This article focuses on the experimental elicitation of pain through heat (thermal) and electrical stimulation while recording physiological, visual, and paralinguistic responses. It aims at collecting valid multimodal data for analyzing pain based on its intensity, quality, and duration.&#160;

分析疼痛对热和电刺激反应的多模态信号

The assessment of pain relies mostly on methods that require a person to communicate. However, for people with cognitive and verbal impairments, existing ...

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats

Complex regional pain syndrome type-I (CRPS-I) is a neurological disease that causes severe pain among patients and remains an unresolved medical condition. However, the underlying mechanisms of CRPS-I have yet to be revealed. It is known that ischemia/reperfusion is one of the leading factors that causes CRPS-I. By means of prolonged ischemia and reperfusion of the hind limb, the rat chronic post-ischemia pain (CPIP) model has been established to mimic CRPS-I. The CPIP model has become a well-recognized animal model for studying the mechanisms of CRPS-I. This protocol describes the detailed procedures involved in the establishment of the rat model of CPIP, including anesthesia, followed by ischemia/reperfusion of the hind limb. Characteristics of the rat CPIP model are further evaluated by measuring the mechanical and thermal hypersensitivities of the hind limb as well as the nocifensive responses to acute capsaicin injection. The rat CPIP model exhibits several CRPS-I-like manifestations, including hind limb edema and hyperemia in the early stage after establishment, persistent thermal and mechanical hypersensitivities, and increased nocifensive responses to acute capsaicin injection. These characteristics render it a suitable animal model for further investigation of the mechanisms involved in CRPS-I.

Provided here is a protocol that details steps to establish an animal model of chronic post-ischemia pain (CPIP). This is a well-recognized model mimicking human complex regional pain syndrome type-I. Mechanical and thermal hypersensitivities are further evaluated, as well as capsaicin-induced nocifensive behaviors observed in the CPIP rat model.

大鼠复杂区域疼痛综合征I型慢性缺血后疼痛模型

Complex regional pain syndrome type-I (CRPS-I) is a neurological disease that causes severe pain among patients and remains an unresolved medical ...

Assessment of Memory Function in Pilocarpine-induced Epileptic Mice

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals&#8217; basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice.

This article presents experimental procedures for assessing memory impairments in pilocarpine-induced epileptic mice. This protocol can be used to study the pathophysiologic mechanisms of epilepsy-associated cognitive decline, which is one of the most common comorbidities in epilepsy.

皮洛卡平诱导癫痫小鼠记忆功能评估

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal ...

Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

在小鼠的 Y-Maze 障碍任务中，慢性应力转移与工作量相关的选择行为

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that ...

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

Published assays for mechanical nociception in Drosophila have led to variable assessments of behavior. Here, we fabricated, for use with Drosophila larvae, customized metal nickel-titanium alloy (nitinol) filaments. These mechanical probes are similar to the von Frey filaments used in vertebrates to measure mechanical nociception. Here, we demonstrate how to make and calibrate these mechanical probes and how to generate a full behavioral dose-response from subthreshold (innocuous or non-noxious range) to suprathreshold (low to high noxious range) stimuli. To demonstrate the utility of the probes, we investigated tissue damage-induced hypersensitivity in Drosophila larvae. Mechanical allodynia (hypersensitivity to a normally innocuous mechanical stimulus) and hyperalgesia (exaggerated responsiveness to a noxious mechanical stimulus) have not yet been established in Drosophila larvae. Using mechanical probes that are normally innocuous or probes that typically elicit an aversive behavior, we found that Drosophila larvae develop mechanical hypersensitization (both allodynia and hyperalgesia) after tissue damage. Thus, the mechanical probes and assay that we illustrate here will likely be important tools to dissect the fundamental molecular/genetic mechanisms of mechanical hypersensitivity.

An Improved Assay and Tools for Measuring Mechanical Nociception in Drosophila Larvae

The goal of this protocol is to show how to perform an improved assay for mechanical nociception in Drosophila larvae. We use the assay here to demonstrate that mechanical hypersensitivity (allodynia and hyperalgesia) exists in Drosophila larvae.

测量 果蝇 拉瓦的机械结节的改进的检测和工具

Published assays for mechanical nociception in Drosophila have led to variable assessments of behavior. Here, we fabricated, for use with Drosophila ...