The authors acknowledge the work that was done by the first author of the IoN-CCI model, Bart Vos&#8224;.

伦理声明:动物治疗和关怀根据委员会的研究和IASP 11的伦理问题的指导方针。该协议被批准的机构伦理委员会。 1.主题<ol><li>使用雄性SD大鼠（250-300g的到港）。 </li><li>房子只在一个殖民地的房间有40-60％的湿度和21±1℃的室温固底笼。 </li><li>使水和食物提供不限量。 </li><li>保持大鼠下，反向12时12小时黑暗/光周期（开灯20小时）。 </li></ol> 2.手术<ol><li>每只鼠，准备两片约6厘米铬肠结扎（5-0）长，并放置在无菌盐水中，以避免干燥和变得僵硬且脆。 </li><li>麻醉与戊巴比妥动物（60毫克/千克，IP），用阿托品（0.1毫克/千克，IP）。通过延长一条腿，pinchi监测麻醉水平纳克脚趾之间的皮肤上用指甲以确保有足够的压力被施加。确保动物不展示自己的肢体。如果有必要，给予额外的戊巴比妥钠。 </li><li>剃鼠的头部，使得中线切开头皮，可制成具有相等的距离前部和后部，​​对眼睛的中心约25毫米。 </li><li>修复老鼠的头一个立体框架或以其他方式固定老鼠的头部。放置在一个加热垫的大鼠，以保持体温。 </li><li>取适量涂抹于双眼眼药膏，以防止干燥损害。 </li><li>用酒精擦洗光头区域，然后优碘。 </li><li>做一个中线头皮切口，露出颅骨和鼻骨。 </li><li>使用的手术显微镜来执行步骤2.9至2.16。 </li><li>解剖轨道自由，由上颌窦，额窦，泪和颧骨骼形成的边缘，用棉签和一对杜蒙钳的。用棉签如此阿克补气血从可能的出血。 </li><li>为了让进入离子，打个擦边球用精密棉签眶内容物，注意不要过度扩张的筛前神经横跨优于离子。解剖离子自由从周围结缔组织，使用精密棉签和一对使用扩频运动杜蒙钳的。用棉签吸收血液可能出血。 </li><li>要执行结扎，推单片铬肠向下沿额骨的一端，内侧与离子和推进几毫米平行和劣于离子。该结扎现在在离子和额骨之间的地方举行。 </li><li>滑的下离子以45度倾斜的杜蒙钳尖端将其放置在靠近结扎。轻轻缩回离子侧面揭示钳结扎和小费。握钳结扎和横向下的离子撤回镊子。 </LI&gt; <li>从眶腔拉出结扎直到结扎的两端从离子或多或少等距。 </li><li>建立从结扎线的两端一个"活结"，让完美的控制收缩的程度和相对滑动的离子结。进一步滑动结以收缩离子，使得神经的直径减小一个可觉量。使在滑结的顶部上的正常结，使得收缩的量保持恒定（即，防止狭缝结打滑）。 </li><li>切连字留下约2毫米的离结自由端。 </li><li>重复同样的过程（步骤2.11至2.15），以从所述第一做一个第二结扎2毫米。 </li><li>对于假手术，执行步骤2.2到2.10。 </li><li>关闭采用涤纶缝线（4-0）头皮切口，让老鼠恢复上一个加热垫。不要让动物无人看管，直到它重新获得足够的利弊ciousness保持胸骨斜卧，并不动物返回给其他动物的公司，直到其完全恢复。 </li><li>为了避免对神经性疼痛的发展先发制人镇痛作用，不施用镇痛手术后疼痛。 </li></ol> 3.行为测试程序<ol><li>允许大鼠适应环境至少8天的时间手术前测试之前的居住条件。 </li><li>手术前测试之前每日三天至少一次，观察者大鼠测试过程。 </li><li>在黑暗的房间光线通过一个60瓦的红色灯泡提供行为测试暂停以上1米的试验区照明中心，但留下的圆周昏暗的房间黑暗的剩余部分的中心。 </li><li>确保有足够的背景噪音，以减少突发听觉刺激的干扰。如果需要的话，提供白噪声。 </li><li>面部护理行为观察<ol><li> Ťransport从殖民地一个老鼠的试验室有盖的塑料保持架没有被褥。注:理想情况下，这应该是最少的外部刺激的短途旅行。 </li><li>放置在有盖的，透明的塑料笼老鼠没有床上用品（LXWXH:24厘米×14厘米×17厘米）的镜像备份在摄像机前。 </li><li>做一个10分钟的记录动物的行为。在录制过程中，要确保实验者不存在于所述测试室。 </li><li>将下一个动物前，清洁观察笼。 </li><li>确保所记录的行为是由实验者谁是盲目的大鼠的实验条件下进行分析。 </li><li>使10分钟的录制过程中，每一面疏导集的记录。注意:面部护理被定义为其中前爪被带到与面部区域接触的运动模式。 </li><li>使两种类型的面梳理行为之间的区别。如果一个序列既不前面和后面由体修饰（即，梳理的身体区域脸部 ​​以外），分类的情节作为分离面的修饰。如果身体梳洗之前或面部美容后立即进行，分类情节脸部护理过程中身体疏导。 </li><li>确定的面部美容发作的次数。 <ol><li>归类面部美容动作之间的时间段不超过4秒为帧内集空间 （即，在单个情节面部美容动作之间的停顿）。 </li><li>归类超过4秒作为一个跨插曲空间 （即，脸部美容动作两集之间的完全中断）面梳理动作之间的时间段。 </li></ol></li></ol></li><li>机械性刺激试验<ol><li>运输大鼠达6只动物从菌落到测试室的基团在有盖的笼与寝具。确保这是最少的外部刺激的短途旅行。 </li><li>放置大鼠个别地置于透明塑料笼寝具（LXWXH:24厘米×14厘米×17厘米）的自由开闭，以便它可以容易地打开和关闭。 </li><li>使用分级系列五·冯·弗雷毛发。注意:弯曲毛发所需的力是0.015克，0.127克，0.217克，0.745克和2.150克。 </li><li> ，观察者大鼠的观察笼并到达运动10分钟。每30秒，打开盖子，轻轻地触摸笼壁用塑料棒。 </li><li>当动物处于嗅/无运动状态 （即，带有四个爪放置在地面上，既不移动也不冻结，但表现出嗅探行为），可应用所述第一的von Frey毛发离子境内靠近vibrissal垫的中心，对周围的mystacial触须毛茸茸的皮肤。 </li><li>评分动物对刺激的响应于属于下列响应类别4之一。 <ol><li>分类完全没有反应，作为比分0。 </li><li>分类的刺激检测（ 即鼠转头向激励对象，激励对象然后探索）的比分是1。 </li><li>分类取款反应（ 即 ，鼠转头慢慢远去，或发生拉它轻快地向后当刺激被应用，有时单个面擦同侧刺激区）的比分2。 </li><li>分类逃生/攻击响应（ 即 ，老鼠避免与刺激物进一步接触，无论是被动地通过移动身体远离刺激物承担对笼壁蹲伏的姿势，或主动通过攻击刺激物，使咬和抓的动作）作为得分3。 </li><li>分类不对称的脸修饰（ 即鼠显示一系列连续的朝向刺激的面部区域至少有三个洗脸笔）作为得分4。 </li><li>在每个动物，申请stimu李强度的升序排列。后一个刺激强度已经被应用到一侧，将其应用到另一侧移动到下一个刺激强度之前。随机化，其中，同侧和对侧侧面受到刺激的顺序。注意，动物必须在一个嗅探/无运动状态的每个刺激前。 </li></ol></li></ol></li></ol>

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The authors have nothing to disclose.

离子的CCI模型中最令人感兴趣的方面是，它提供了自发的，非诱发（神经性）疼痛的唯一措施。神经性疼痛的大多数动物实验中，使用脊神经模型，专门解决nocifensive 行为 （例如，发声和戒断反应），反映过敏机械或热的刺激12。然而，患者的主要临床抱怨是持续性疼痛，痛觉过敏没有异常性疼痛或13。 本文章介绍了神经性疼痛以下离子CCI，孤立的脸?...

损坏的体感神经最常导致感觉丧失。它不很好地理解为什么和怎样，在一些情况下，外周神经损伤引起的慢性疼痛。其结果是，痛苦神经病仍然是具有挑战性的条件来治疗1和导致大幅度减少生活2-3的患者的生存质量。动物模型是研究的现有的和新开发的药物的疗效，并确定参与神经性疼痛的发展和维持的病理生理机制的一个重要工具。在对平移疼痛研究的主要挑战是确定和衡量自发性疼痛的动物（ 即 ，生理，行为或其他表现，表明疼痛的动物的存在是不被用探测被敏锐地叠加在对象的基础条件刺激的挑战）。此过程的总体目标是手术诱导眶下神经损伤的大鼠，导致两者自发的发展和诱发可用于研究参与三叉神经性疼痛和其治疗机制nocifensive行为。 导演，孤立的脸修饰是大鼠自发性神经病理性疼痛唯一的措施。以下眶下神经的慢性挤压伤（CCI）（离子），大鼠表现出变化自发行为和响应于触觉刺激的，指示的持续性疼痛和机械异常性疼痛4。以下离子的CCI，大鼠显示出增加的和非对称面的修饰活性， 即 ，与洗面笔划主要涉及神经损伤离子领土。与此相反的面的伤害性刺激（例如，福尔马林注射）5，非疼痛感觉障碍（即，单侧触须削波，麻药眶下神经阻滞，矿物油对VIBRI应用SSAE）没有或只有非常简要（即，发病后的第一分钟）诱导梳理行为6面对一个显著变化。得出的结论是离子CCI后，这种不正常的疏导是在受伤的神经境内自发的，强烈的厌恶感觉一种行为表现。在离子CCI大鼠这种行为带有很强的相似观察患者自发性疼痛。进一步的研究发现面部修饰行为之间的一个重要区别是一个更一般的身体修饰行为的一部分（ 即"身体美容在脸上疏导"），这在很大程度上仍然不受离子CCI和nocifensive面部美容既不之前也不随后体修饰（即，"分离的面部美容"），其中离子的CCI 7-9后显著增加。药理学上，在身体护理面部护理构成良好的控制测量非特异性药物作用（ <em&gt;例如，镇静）可能损害运动功能。在两种类型的脸的修饰的前肢运动是完全一样的。 以下离子的CCI，大鼠也响应于触觉刺激的，指示机械异常性疼痛4，10的呈现的改变。在第一周离子CCI后（多个），大鼠不再到轻度或中度触觉（即，的von Frey响应）的刺激。这种低反应，然后突然用一种极端的高反应性，从而即使是很微弱的刺激强度挑起nocifensive行为所取代。高反应性的可发性大鼠之间变化，但经过三至四周手术后最大鼠都成为高反应性。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Chromic catgut</td>
			<td>Dynek&#160;</td>
			<td>CG504</td>
			<td></td>
		</tr>
		<tr>
			<td>Nembutal&#160; (pentobarbital)</td>
			<td>Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Atropine</td>
			<td>Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Clippers for small animals - Favorita II</td>
			<td>Aesculap</td>
			<td>GT104</td>
			<td></td>
		</tr>
		<tr>
			<td>Stereotaxic instrument</td>
			<td>Stoelting</td>
			<td>51600</td>
			<td></td>
		</tr>
		<tr>
			<td>Ophthalmic ointment (Liposic)</td>
			<td>Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Homeothermic monitor system</td>
			<td>Harvard Apparatus</td>
			<td>PY8 50-7221-F</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton applicator</td>
			<td>Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Precision cotton swab</td>
			<td>Qosina</td>
			<td>10225</td>
			<td></td>
		</tr>
		<tr>
			<td>Operation microscope</td>
			<td>Kaps</td>
			<td>SOM 62</td>
			<td></td>
		</tr>
		<tr>
			<td>Dumont #5 forceps</td>
			<td>Fine Science Tools</td>
			<td>11251-10</td>
			<td></td>
		</tr>
		<tr>
			<td>Dumont forceps - Micro-blunted tips (#5/45)</td>
			<td>Fine Science Tools</td>
			<td>11253-25</td>
			<td></td>
		</tr>
		<tr>
			<td>Scissors - blunt tips</td>
			<td>Fine Science Tools</td>
			<td>14574-09</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyester sutures - Mersilene (4-0)</td>
			<td>Ethicon</td>
			<td>R871H</td>
			<td></td>
		</tr>
		<tr>
			<td>Digital video camera</td>
			<td>Sony</td>
			<td>HDR-CX330E</td>
			<td></td>
		</tr>
		<tr>
			<td>Semmes-Weinstein Von Frey Aesthesiometer kit</td>
			<td>Stoelting</td>
			<td>58011</td>
			<td></td>
		</tr>
	</tbody>
</table>

chronic constriction injury of the rat's infraorbital nerve (ion-cci) to study trigeminal neuropathic pain

动物模型是研究的神经性疼痛的病理生理学和药理学的重要工具。这份手稿描述了外科手术和行为过程来研究三叉神经性疼痛的影响。满足三叉神经病疼痛综合症的特异性，眶下神经（离子）被松结扎神经经受慢性挤压伤（CCI）。一内部轨道的方式在这里呈现给揭露和结扎离子眶腔。离子结扎后，大鼠表现出变化自发行为和响应于的von Frey毛发刺激是表示持续性疼痛和机械异常性疼痛。两相可在的行为变化的发展来限定。在第一周离子CCI（阶段1），只显示出增加的和不对称的脸修饰活动， 即用洗面招主要针对神经损伤离子领土。它又分为脸部克之间进行ooming行为是更一般的身体梳理行为，这仍然基本不受离子的CCI的一部分，并且面对疏导既不是前面和后面由身体修饰，其中离子的CCI后显著增加。在此期间，响应于离子领土的机械刺激被降低。这种低反应突然由一个极端的高反应性，从而即使是很微弱的刺激强度惹nocifensive行为（第2阶段）所取代。这些行为改变和报道的面部疼痛征兆之间的相似性现象（即，响应于脸部的伤害性刺激）建议感觉迟钝/感觉异常和机械异常性疼痛在结扎离子领土的存在。

离子CCI大鼠表现出强烈的手术后增加的时间花费在分离面疏导（图1）的量。在第一手术后一周结束的增加的峰值，然后在接下来的数周内下降。最近的研究发现，面部修饰，以长达三个星期显著增加。在假手术组脸部美容的行为或多或少受到影响。 ION-CCI老鼠也表现出几乎完全没有反应的离子领土同侧机械刺激的第一个手术后一周（ 图2）中。在接?...

Watch this Scientific Journal Video about Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain at JoVE.com

Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat&#8217;s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia.

老鼠的眶下神经（ION-CCI）研究三叉神经性疼痛性损伤

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral ...

chronic-constriction-injury-rat-s-infraorbital-nerve-ion-cci-to-study

Research

JoVE Journal

Medicine

Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study Trigeminal Neuropathic Pain

19.3K 次观看.  University of Antwerp. This manuscript describes a rodent model to study trigeminal neuropathic pain. The methods described include surgical procedures to perform a chronic constriction injury of the rat’s infraorbital nerve and the post-surgical behavioral tests to measure the changes in spontaneous and evoked behavior that are indicative of persistent pain and allodynia. 

视频: Chronic Constriction Injury of the Rat's Infraorbital Nerve IoN-CCI to Study Trigeminal Neuropathic Pain

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).
The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.
Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.
This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

主动脉原位移植大鼠模型，研究慢性血管病变的发展

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

科研

医学

The Spared Nerve Injury (SNI) Model of Induced Mechanical Allodynia in Mice

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared nerve injury (SNI) model induces symptoms of neuropathic pain such as mechanical allodynia i.e. pain due to tactile stimuli that do not normally provoke a painful response [1]. 
The SNI mouse model involves ligation of two of the three branches of the sciatic nerve (the tibial nerve and the common peroneal nerve), while the sural nerve is left intact [2]. The lesion results in marked hypersensitivity in the lateral area of the paw, which is innervated by the spared sural nerve. The non-operated side of the mouse can be used as a control. The advantages of the SNI model are the robustness of the response and that it doesn&#x2019;t require expert microsurgical skills.
The threshold for mechanical pain response is determined by testing with von Frey filaments of increasing bending force, which are repetitively pressed against the lateral area of the paw [3], [4]. A positive pain reaction is defined as sudden paw withdrawal, flinching and/or paw licking induced by the filament. A positive response in three out of five repetitive stimuli is defined as the pain threshold. 
As demonstrated in the video protocol, C57BL/6 mice experience profound allodynia as early as the day following surgery and maintain this for several weeks.

The Spared Nerve Injury SNI Model of Induced Mechanical Allodynia in Mice

The Spared Nerve Injury animal model is described here as a mouse model of peripheral neuropathic pain following partial denervation of the sciatic nerve by lesioning the tibial and common peroneal nerve branches, leaving the remaining sural nerve intact. Behavioral modification resulting from mechanical allodynia is quantified by von Frey filaments.

幸免神经损伤（SNI）模型引起的机械触感小鼠

Peripheral neuropathic pain is a severe chronic pain condition which may result from trauma to sensory nerves in the peripheral nervous system. The spared ...

Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of the population1,2. Symptoms include spontaneous (tingling, burning, electric-shock like) pain, dysaesthesia, paraesthesia, allodynia (pain resulting from normally non-painful stimuli) and hyperalgesia (an increased response to painful stimuli). The sensory symptoms are co-morbid with behavioural disabilities, such as insomnia and depression. To study chronic neuropathic pain several animal models mimicking peripheral nerve injury have been developed, one of the most widely used is Bennett and Xie's (1988) unilateral sciatic nerve chronic constriction injury (CCI)3 (Figure 1). Here we present a method for performing CCI and testing pain hypersensitivity.
CCI is performed under anaesthesia, with the sciatic nerve on one side exposed by making a skin incision, and cutting through the connective tissue between the gluteus superficialis and biceps femoris muscles. Four chromic gut ligatures are tied loosely around the sciatic nerve at 1 mm intervals, to just occlude but not arrest epineural blood flow. The wound is closed with sutures in the muscle and staples in the skin. The animal is then allowed to recover from surgery for 24 hrs before pain hypersensitivity testing begins.
For behavioural testing, rats are placed into the testing apparatus and are allowed to habituate to the testing procedure. The area tested is the mid-plantar surface of the hindpaw (Figure 2), which falls within the sciatic nerve distribution. Mechanical withdrawal threshold is assessed by mechanically stimulating both injured and uninjured hindpaws using an electronic dynamic plantar von Frey aesthesiometer or manual von Frey hairs4. The mechanical withdrawal threshold is the maximum pressure exerted (in grams) that triggers paw withdrawal. For measurement of thermal withdrawal latency, first described by Hargreaves et al (1988), the hindpaw is exposed to a beam of radiant heat through a transparent glass surface using a plantar analgesia meter5,6. The withdrawal latency to the heat stimulus is recorded as the time for paw withdrawal in both injured and uninjured hindpaws. Following CCI, mechanical withdrawal threshold, as well as thermal withdrawal latency in the injured paw are both significantly reduced, compared to baseline measurements and the uninjured paw (Figure 3). The CCI model of peripheral nerve injury combined with pain hypersensitivity testing provides a model system to investigate the effectiveness of potential therapeutic agents to modify chronic neuropathic pain. In our laboratory, we utilise CCI alongside thermal and mechanical sensitivity of the hindpaws to investigate the role of neuro-immune interactions in the pathogenesis and treatment of neuropathic pain.

Due to the simplicity of surgery and the robust behavioural outcome, chronic constriction of the sciatic nerve is one of the pre-eminent animal models of neuropathic pain. Within 24 hrs following surgery, pain hypersensitivity is established and can be quantitatively measured using a von Frey aesthesiometer (mechanical test) and plantar analgesia meter (thermal test).

慢性缩窄大鼠坐骨神经疼痛过敏测试

Chronic neuropathic pain, resulting from damage to the central or peripheral nervous system, is a prevalent and debilitating condition, affecting 7-18% of ...

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Breathing-controlled Electrical Stimulation BreEStim for Management of Neuropathic Pain and Spasticity

The purpose is to present a new method, breathing-control electrical stimulation (BreEStim) for management of neuropathic pain and spasticity.

呼吸控制电气的刺激（BreEStim）的神经性疼痛和痉挛的管理

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. ...

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination, as well as nocturia and general pelvic pain, especially upon bladder filling or voiding. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. One such murine model is urinary bladder distension (UBD). In this model, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure, wires in the superior oblique abdominal muscles record electrical activity from the muscle. This activity is known as the visceromotor response (VMR) and is a reliable and reproducible measure of nociception. Here, we describe the steps necessary to perform this technique in mice including surgical manipulations, physiological recording, and data analysis. With the use of this model, the coordination between primary sensory neurons, spinal cord secondary afferents, and higher central nervous system areas involved in bladder pain can be unraveled. This basic science knowledge can then be clinically translated to treat patients suffering from IC/BPS.

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized in part by pelvic pain. In order to study nervous system contributions to the condition, a physiological model of urinary bladder pain is used in mice and rats.

膀胱胀诱发内脏运动反应为膀胱疼痛小鼠模型

Approximately 3-8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition ...

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the &#34;cuff model&#34; of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

Neuropathic pain is a consequence of a lesion or disease affecting the somatosensory system. The &#8220;cuff model&#8221; of neuropathic pain in mice consists of the implantation of a polyethylene cuff around the main branch of the sciatic nerve. Mechanical allodynia is tested using von Frey filaments.

神经病理性疼痛小鼠坐骨神经掴型号

Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in ...

Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration.

We present a surgical protocol detailing how to perform a cut or crush axotomy on the facial nerve in the mouse. The facial nerve axotomy can be employed to study the physiological response to nerve injury and test therapeutic techniques.

面神经干切断小鼠:模型，研究运动神经元损伤反应

The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and ...

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed.
This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

Treating chronic or neuropathic facial pain can be challenging when medical or standard treatment fails. Subcutaneous nerve field stimulation is the least invasive form of neuromodulation and is used for chronic back pain. We applied this technology to treat chronic and neuropathic trigeminal facial pain.

皮下三叉神经场刺激难治性面部疼痛

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. ...

Development of Recombinant Proteins to Treat Chronic Pain

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates for treating debilitating pain conditions due to their capacity to regulate aberrant neuro-immune interactions. However, physiologically they work in a network of various cytokines, and therefore their therapeutic effect may not be optimal when used as stand-alone drugs. To overcome this limitation, we developed a fusion protein of the anti-inflammatory cytokines IL4 and IL10. Here, we describe the methods for production and quality control of IL4-10 recombinant fusion protein and we test the effectiveness of the IL4-10 fusion protein to resolve pain in a mouse model of persistent inflammatory pain.

In this paper we provide details for the methods of production and quality control of an IL4-10 recombinant fusion protein. We also show how to test the effectiveness of this protein to resolve pain in a mouse model of inflammatory pain.

重组蛋白治疗慢性疼痛的研究进展

Chronic pain is difficult to treat and new approaches to resolve persistent pain are urgently needed. Anti-inflammatory cytokines are promising candidates ...

Employing the Forced Oscillation Technique for the Assessment of Respiratory Mechanics in Adults

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and diseased individuals. FOT, a complementary method to traditional pulmonary function testing, utilizes a range of oscillatory frequencies superimposed on tidal breathing to measure the functional relationship between airway pressure and flow. This passive assessment provides an estimate of respiratory system resistance (Rrs) and reactance (Xrs) that reflect airway caliber and energy storage and dissipation, respectively. Despite the recent increase in popularity and updated Technical Standards, clinical adoption has been slow which relates, in part, to the lack of standardization regarding the acquisition and reporting of FOT data. The goal of this article is to address the lack of standardization across laboratories by providing a comprehensive written protocol for FOT and an accompanying video. To illustrate that this protocol can be utilized irrespective of a particular device, three separate FOT devices have been employed in the case examples and video demonstration. This effort is intended to standardize the use and interpretation of FOT, provide practical suggestions, as well as highlight future questions that need to be addressed.

As the use of forced oscillation technique (FOT) is increasingly utilized to characterize respiratory mechanics, there is a need to standardize methods with respect to nascent technical guidelines and various manufacturer's recommendations. A detailed protocol is provided including FOT assessment and interpretation for two cases to facilitate the standardization of methods.

采用强制振荡技术评估成人呼吸力学

There is increasing interest in the use of the forced oscillation technique (FOT) or oscillometry to characterize respiratory mechanics in healthy and ...