这项研究是支持的，部分由美国国立卫生研究院资助（NIH / NINDS R01NS060774的NIH / NICHD / NCMRR的R24 HD050821-08根据分包芝加哥康复研究所）。作者感谢克雷格Ditommaso，MD为他的编辑和有益的建议。

以下BreEStim协议可应用于两个手指的屈肌痉挛和神经性疼痛管理。主要的区别在于表面电极放置和调整刺激强度。这些差异是为每个应用程序中详细解释。 1。主题准备和安装<ol><li>舒适座椅的主题。将武器和双手舒适的治疗表上。 </li><li>识别和定位感兴趣的区域的表面电极放置。 <ol><li>的手指伸肌痉挛的管理，触诊腹部肌肉电刺激确认。 </li><li>疼痛管理中，找到穴位的前臂24内关和Weiguan对同侧侧的利益， 例如 ，截肢17，或侧面，更多的症状， 例如 ，SCI。内关穴是位于约3指宽以上的掌侧腕关节皱折d在前臂（ 即 ，远端前臂的1/6）24（ 图3）的内侧和外侧板之间的中间。 Weiguan是对应的内关穴，位于中的前臂背侧24。 </li></ol></li><li>修剪到约2厘米x 2cm见方的每个自粘电极到重点和孤立的电刺激。 <ol><li>痉挛的管理，将阴极手指伸肌肌腹（ 图4）。的阳极​​连接到一个站点1〜2厘米到阴极的远端。优化的网站时，在阳极和阴极引出最大的和孤立的手指与最小的手腕响应扩展响应。 </li><li>疼痛管理，将内关穴，阴极电极和阳极电极上Weiguan。 </li></ol></li><li>连接表面电极到电刺激（Digitimer DS7A，英国， <a href="http://www.digitimer.com" target="_blank">www.digitimer.com</a> ）。 </li><li>固定到位口罩。仔细选择尺寸的口罩，以适应个人的脸，以防止空气泄漏，并提供舒适的戴面具（ 图5）。 </li><li>面罩连接到描记系统（系列1110A，汉斯·Rodolph公司;美国密苏里州堪萨斯城， <a href="http://www.rudolphkc.com" target="_blank">http://www.rudolphkc.com</a> ）。 </li></ol> 2。教学对自愿呼吸自愿呼吸，特别是自愿吸入，这种干预起着至关重要的作用。吸入被定义为自愿付出努力的深入和快速吸入。指导的对象接受一个单一的孤立深深吸了一口气，类似常规深呼吸，更快，更强的。有没有必要执行自愿呼气强迫吸入在一个呼吸周期前。让被摄体有8〜10个实践试验，以了解的说明。 3。电刺激SettiNGS <ol><li>作为一个单一的方波脉冲0.1ms的时间设置一个单一的电刺激。电刺激的强度是不同的应用程序不同。由于单个电刺激每次交付，有没有必要设置的频率参数。 </li><li>痉挛的管理，确定1）孤立的手指延长反应时，最低限度地参与腕关节的反应引起的电刺激的强度; 2）主题可以容忍的最高级别。刺激强度的绝对量可能会有所不同不同科目。鼓励强度最高的主题可以容忍，以达到最佳的结果。 </li><li>疼痛管理，让被摄体确定的增量变化的刺激强度。的起始强度为零。最高级别是最大的刺激或输出的主题可以容忍的水平。然而，明确指示SUBJECT，不适或困苦，甚至是"厌恶"的电刺激治疗的一部分，因此，鼓励主体选择的主题可以容忍的最高级别。 </li></ol> 4。控制电刺激<ol><li>写一个自定义的LabVIEW（美国国家仪器，奥斯汀，德克萨斯州）的程序来控制提供电刺激在两个方面:BreEStim和电刺激。 </li><li>呼吸控制的电的刺激（BreEStim）（ 图6）: <ol><li>确定气流速度峰值在自愿吸入， 即在最深和最快速的吸入。 </li><li>确定阈值是40％，气流速度峰值。值得注意的是，在正常呼吸，以鼓励更多更快地自愿呼吸的气流速度高于设定的阈值。 </li><li>然后设置触发功能。当一个孤立的自愿吸入的瞬时气流速率达到或超过阈值，第ËLabVIEW程序触发，并提供一个单一的电刺激与预设的持续时间和强度16。允许休息时要求的主题。 </li></ol></li><li>随机触发电刺激（电刺激）: <ol><li>允许这个问题没有具体说明，呼吸正常呼吸。 </li><li> LabVIEW程序随机提供了一个单一的电刺激与预设的持续时间和强度，每4至7秒。同样，休息时要求的主题。 </li></ol></li></ol> 5。剂量BreEStim 建议每个会话的治疗有100至120 BreEStim的刺激。它持续约30-40分钟。 6。记录和监控<ol><li>请确保没有空气泄漏口罩，因为自愿吸入在本协议中起着重要的作用。 </li><li>监控低氧血症，过度通气的迹象时的主题戴口罩。铝用于此目的的当事人的要求低休息。 </li><li>记录任何副作用，耐受性的自愿通过面罩呼吸，和任何的心理和社会影响。 </li><li>疼痛管理，记录， 即任何减少疼痛视觉模拟评分（VAS）57和效果的持续时间。使用修改后的增值服务（MVAS）进一步量化的效果，减轻疼痛，减少多大的痛苦和持续多久（"减少"×小时）。也记录了每个会话的平均强度电刺激的强度变化，因为在每个会话的处理。 </li><li>痉挛的管理，记录修改的Ashworth量表（MAS）的目标肌肉和其他临床测量值，包括力量，感觉和运动范围。 </li></ol>

呼吸控制的电子模拟的骨骼肌肉（发明者:SL，正在申请的专利，申请号12146176）的方法和设备。

呼吸控制电气的刺激（BreEStim）的，在上述两种情况下，已经证明在上述病人与慢性中风患者痉挛的管理和后续的手部功能恢复16，以及管理中心起源的神经性疼痛的临床疗效脊髓损伤或周边起源于膝盖以上截肢病人17。这种增强的临床疗效和更广泛的临床应用BreEStim是由于其独特的方法。在短窗口的自愿呼吸相关的皮层和皮层下激活40-51电刺激有针对性的干预可增强其临床疗效，通过内在的生理耦合， 例如 ，呼吸电机联轴器痉挛管理16。在这种干预，自愿的呼吸变得至关重要，特别是自愿的灵感。患者教育<html>正确的呼吸技巧和精确的测量呼吸参数（ 例如 ，不漏气）的BreEStim干预措施，以防止故障。 新的干预措施协议 - BreEStim，有几个好处，除了更好的疗效和更广泛的应用。 BreEStim以病人为中心的。BreEStim鼓励患者积极参与，因为需要自愿呼吸17。患者感觉他们积极参与管理他们的痛苦，而不是一个被动的参与者在自己的照顾"。例如，病人控制电刺激的强度，从零起来的最高水平，患者能耐受17。这可能会提高其治疗依从性。肌电触发电刺激还涉及积极参与36，但病人无法控制的电刺激的强度。 ntent"&gt; BreEStim需要一个综合的，系统的方法。在以前的研究[17]表明，不同的疼痛的应对机制集成到一个协议，包括电刺激，针灸，厌恶性刺激，自愿的呼吸和全身的影响。 ，患者是能够忍受高的电刺激，从而增强镇痛作用。使用这种综合的，系统的方法，这种积极的反馈循环（活化的奖励制度）的结果在更大的临床疗效。自愿呼吸的某些信号也可以被用来识别系统之间的交互的时间窗。因此，BreEStim可以施加到严重痉挛患者，这些患者通常无法执行自主收缩力，从而"干净"的的EMG信号从目标肌肉不可在EMG触发电刺激，肌电图信号有针对性的肌肉（&lt;em&gt;的如手指伸肌）需要触发电刺激。因此，应用程序有轻度到中度痉挛患者的肌电触发电刺激是有限的。 BreEStim是一种非侵入性，非药物治疗，这是非常重要的，因为病人往往需要长期使用药物，慢性疼痛和痉挛的药物有副作用，有时是非常严重的。可能的副作用包括成瘾，过量服用，停药后症状，便秘等，这些潜在的副作用是可以避免的在BreEStim治疗。 BreEStim是另一种选择，另一种非药物治疗有较好的止痛效果是很重要的，尤其是在神经性疼痛是难以管理。例如，只有7％的被调查者神经性疼痛的药物治疗是有效的，以下SCI在问卷调查58。 总之，这样的呼吸驱动的的刺激，BreEStim，根据新发现的耦合激活内在的生理现象，在自主呼吸。 BreEStim协议已经证明神经性疼痛的临床疗效和中风后痉挛管理。进一步的研究是必要的检查背后的机制介导的干预作用。更重要的是，有可能是尚未分辨的其他应用程序。

电刺激（电刺激类）是指肌肉或神经施加电流，以实现功能和治疗目标。它已被广泛用于各种临床设置， 例如 ，经皮神经电刺激（TENS）的疼痛管理1，腓总神经电刺激足下垂，神经肌肉电刺激（NMES）激活和加强肌肉瘫痪或削弱。当NMES用于实现一个功能的任务，它被称为功能性电刺激（FES）4。肌电图（EMG）触发的神经肌肉刺激已用于增加电刺激的有效性在电机恢复5-14和痉挛减少中风后7天，15。在本文中，一个新的电刺激协议 - 呼吸控制的电刺激（BreEStim）介绍，根据最近的研究结果对systemiC EFFECT自愿呼吸16，17。 经皮神经电刺激（TENS）是一种非药物疼痛管理方式1。 TENS是无创，价廉，安全和易于使用的18。 TENS通常适用于不同的频率，强度和刺激的脉冲持续时间为规定的治疗时间。 TENS已被应用到各种疼痛病况，包括神经性疼痛。的临床效果TENS是有争议的，特别是在脊髓损伤（SCI），截肢（见点评1，19，20）。其机制可能是闸门控制学说21和释放内源性阿片类药物22，23。从中国传统医学针灸的疼痛管理是另一种非药物的方式。它已被广泛接受中西医24。在现代针灸，已取代了传统的针灸针表面元素ctrode（或同等学历）。一个专门的电极是比传统的穴位电刺激传递。本变形例中被称为电针25，26。针灸和电都是有效的镇痛通过释放内源性阿片类药物27，28。电的影响通常是可靠的，但效果是依赖于交付电刺激的强度和频率。不同频率的电刺激产生不同的内源性阿片类药物，镇痛效果是纳洛酮可逆26，27。最近，它已被发现，重复的痛苦刺激（厌恶）导致显着的疼痛衰减。引起的疼痛衰减是不纳洛酮可逆的29。整合这些痛苦应对机制（针灸，电刺激厌恶），一个可能的新的干预措施，可以提高其临床疗效。 5-10，12-14，34。中风患者手部功能的恢复是非常重要的，却又是非常具有挑战性的。大约三分之一的所有的人发生中风的人，都会有一些残留的上肢30-32减值，手部功能的主要障碍在33。肌电触发的神经肌肉电刺激干预协议涉及一个特定的运动的自愿性收缩的伸肌开始，直到肌肉活动达到阈值水平。尽快EMG活动达到目标阈值，一个辅助的电刺激开始，以方便的动作。这种干预的协议是优于定期NMES运动功能恢复6，7。蔡并于35指出，所有随机对照研究报告使用这种干预可以改善运动功能协议，轻度至中度受损的患者改善最。它是最有可能的是，这种干预优势，积极参与病人（通过设置一个目标EMG阈值），这导致复苏的可测量的变化，以及改变皮质6，7。这是所支持的最近的功能性磁共振成像研究显示，一个NMES组治疗后，在同侧体感皮层，皮质强度显着增加，较对照组36。此外，电刺激可能也有助于减轻痉挛中风后7天，15，但效果是短暂的，大约30分钟后，电刺激37。相比之下，我们的呼吸控制的电刺激（BreEStim）最近发明的一个长期持久的影响痉挛减少，即使在单届治疗16。 人的呼吸是一个非常独特的电动机行为。它可以控制本能地（自动呼吸）， 例如 ，在睡眠过程中，还主动在需要时（自愿的呼吸）， 例如 ，唱歌，演讲等，在自愿的呼吸，人类需要主动通过自愿皮层激活抑制自主呼吸控制（ "皮质呼吸中枢"）38，39。脑成像研究40-51表现出了广泛的呼吸有关的双边皮质区，包括初级运动皮层（M1），前运动皮层，辅助运动区，小学和中学的体感皮层，脑岛，前扣带皮层参与杏仁核和背外侧前额叶皮层。岛被称为具有较强的连接到脑干的中心，并参与疼痛处理52。在自主呼吸过程中，灵感是积极的，而呼气是被动的，主要是靠后坐力的胸壁。同样，意志灵感激活呼吸系统相关的皮质和皮质下区域相比，意志期满46。这些在自主呼吸激活的皮质和皮质下区域也参与了不同的功能53，如肌肉紧张，疼痛，姿势，情绪，言语等，因此，也不是没有道理，在呼吸调节等功能的交互关联。 最近，我们已经发现，在自主呼吸的呼吸和运动系统之间存在相互作用。具体而言，存在手指伸展启发耦合16，54-56。当电刺激传递到手指伸肌在自愿呼吸的吸气阶段，一个长期持久的效果，减少手指屈肌痉挛（肌肉张力）在慢性中风患者观察16。在另一项研究中17，命中率幻肢痛的病人与上述千牛电子工程的截肢消失后，治疗的BreEStim，但再28天后出现意外后持续电刺激。本案例研究提供了一个独特的机会，了解伤害性刺激的神经性疼痛（拍摄幻肢痛）的情感成分被修改的BreEStim处理，但后来一个偶然的刺激所引发的。这些语气和减轻疼痛的观察表明，自愿的呼吸，尤其是灵感，可以集成到电刺激在神经性疼痛管理和中风后痉挛的管理范式来提高其疗效。 案例介绍案例1:中风后痉挛性管理患者是一名69岁男性，右侧肢体偏瘫继发于22个月前中风。他病情稳定，已出院门诊物理和占用pational治疗方案。无脑成像效果在实验的时间。他的弱点在他的右侧，但能独立行走，没有辅助设备。他有残余自愿的手指屈伸，但活动范围有限，在他的右掌指关节（MCP）的运动，从90°到70°，MCP屈曲， 即不能够充分地打开他的手和手指的功能使用。他的右手手指屈肌肌张力适度增加。改良Ashworth量表（MAS）是1 +。 ，然而，他的右手和手指的感觉是完整的光触摸。 ，他收到约30分钟BreEStim，到手指伸肌。他的手指屈肌痉挛减少到最低限度（MAS = 0）和自愿的手指延伸成为接近正常后，立即处理。以及这名患者恢复了他的手部功能。他报告说，他能切肉刀和按钮衬衫，他受损的手。铁道部Ë引人注目的是，在恢复期间保留至少8周的随访（ 图1）。 案例2:神经性疼痛管理患者是一名40岁的男性遭遇了4.5年前在车祸脊髓损伤，导致T8 ASIA脊髓损伤。病人主诉的神经性疼痛的伤害，而他没有其他有效的医疗问题。他一直稳定在疼痛制度前2个星期的治疗。他接受电刺激（每天连续五天的一次会议），等待1周为一个冲刷，然后用相同剂量（一个会话，连续5天）​​每天收到BreEStim。每个疗程120的刺激（电刺激或BreEStim）的。表面电极置于腧穴（内关Weiguan）的右前臂。改进的视觉模拟评分法（MVAS）使用，比较各项干预措施的效果（电刺激BreEStim）的。由于SHOWN 图2中，BreEStim在BreEStim有减轻疼痛的效果比电刺激，但第2天，当病人有尿路感染（UTI）成功地用抗生素治疗。电刺激的强度之间电刺激和BreEStim的（ 图2）相似。他两种干预耐受以及（从刺激的最大输出强度的被使用），即使在泌尿道感染。在整个实验期间（4周），主体保持相同的止痛药的剂量和疗程。进行BreEStim和电刺激治疗会在同一天的时间（上午11点至中午之间），这样，在疼痛等级的变化可能是由于刺激作用，没有昼夜变化。

<table border="1"><tbody><tr><td> 的试剂/材料名称 </td><td> 公司 </td><td> 目录编号 </td><td> 评论 </td></tr><tr><td>起搏器</td><td> Digitimer </td><td> DS7A </td><td> <a href="http://www.digitimer.com/" target="_blank">http://www.digitimer.com</a> </td></tr><tr><td>的呼吸系统</td><td>汉斯Rodolph公司</td><td>系列1110A </td><td> <a href="http://www.rudolphkc.com/" target="_blank">http://www.rudolphkc.com</a> </td></tr></tbody></table>

breathing-controlled electrical stimulation (breestim) for management of neuropathic pain and spasticity

电刺激（电刺激类）是指肌肉或神经施加电流，以实现功能和治疗目标。它已被广泛用于在不同的临床设置。根据相关的系统性影响自愿在自主呼吸的呼吸和内在的生理系统之间的相互作用最近发现，一个新的电刺激协议，呼吸控制的电气的刺激（BreEStim），已被开发，以增加电刺激。在BreEStim，单脉冲电刺激触发和交付给一个孤立的自愿的启示的气流速率达到阈值时，该目标区域。 BreEStim集成了内在的生理作用，在自主呼吸被激活，并显示了良好的临床疗效。代表性应用，BreEStim报告与详细的管理协议:中风后手指弯曲或痉挛和神经性疼痛的脊髓损伤。

管理神经病理性疼痛的脊髓损伤和中风后手指屈肌痉挛，呼吸控制的电的刺激（BreEStim）已显示出良好的临床疗效。痉挛减少后BreEStim治疗取决于预处理条件的严重程度。正如图1中所示，手指的屈肌痉挛BreEStim治疗后大大降低。从MAS 1 +手指屈肌痉挛已经减少到最低限度（MAS = 0）。病人可以开他的手和手指功能的使用。重要的是要注意，其他病人可能不具有相同程度的痉挛减少和功能的改善。在患者体内有严重的手指屈肌痉挛（MAS = 3）和无残余自愿手指延伸（如在图4中所示），手指的屈肌痉挛减少MAS = 1。这使得它更容易为病人到她的手指范围内，但不还原功能使用她公顷第二。 BreEStim还演示了更好和更长疼痛的削减效果。 图2示出 ，相似的电刺激的强度，BreEStim有更好的结果，而不是规律的电刺激。然而，BreEStim并不会影响第2天疼痛评分，当病人有尿路感染。这表明，BreEStim没有疼痛减轻疼痛的效果，当感染混淆。 在BreEStim自愿呼吸起着关键的作用。重要的是要选择适合病人口罩（ 图5），以防止空气泄漏。的气流速度是比较低的，在正常的呼吸（1.6升/秒， 图6）。有力的自愿吸入会大大增加的空气流率（约8升/秒）。表面电极的放置也很重要。中详细描述，并在图3和图4所示，安置的疼痛和痉挛管理是不同的。这是必要的，要注意该位置的手指伸肌的肌腹的结果可能会改变萎缩，中风后的畸形。 <img alt="图1" src="/files/ftp_upload/50077/50077fig1.jpg" /> 图1的手姿势前和后BreEStim的比较。中风患者开他的手后BreEStim。 <img alt="图2" fo:content-width="4.5in" fo:src="/files/ftp_upload/50077/50077fig2highres.jpg" src="/files/ftp_upload/50077/50077fig2.jpg" /> 图2。减轻疼痛的BreEStim和电刺激的影响。 <img alt="图3" src="/files/ftp_upload/50077/50077fig3.jpg" /> 图3。针内关穴的位置。请注意，内关外关是对应的的前臂背侧。 <img alt="图4" src="/files/ftp_upload/50077/50077fig4.jpg" /> 图4。的手指伸肌表面电极的位置。 <img alt="图5" src="/files/ftp_upload/50077/50077fig5.jpg" /> 图5。的患者在BreEStim。表面电极被放置在关和外关。 <img alt="图6" fo:content-width="4.5in" fo:src="/files/ftp_upload/50077/50077fig6highres.jpg" src="/files/ftp_upload/50077/50077fig6.jpg" /> 图6。实时测量空气流速，在自愿的灵感和休息的灵感。请注意，气流率要高得多，在自愿的灵感不是依赖灵感。值得注意的是，患者的呼吸被中断由电刺激。

Watch this Scientific Journal Video about Breathing-controlled Electrical Stimulation BreEStim for Management of Neuropathic Pain and Spasticity at JoVE.com

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

其目的是为了提出了一种新的方法，呼吸控制电气的刺激（BreEStim）的管理神经性疼痛和痉挛。

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. ...

breathing-controlled-electrical-stimulation-breestim-for-management

Research

JoVE Journal

Medicine

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

22.9K 次观看.  University of Texas Health Science Center at Houston. 其目的是为了提出了一种新的方法，呼吸控制电气的刺激（BreEStim）的管理神经性疼痛和痉挛。

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

Programmed Electrical Stimulation in Mice

Genetically-modified mice have emerged as a preferable animal model to study the molecular mechanisms underlying conduction abnormalities, atrial and ventricular arrhythmias, and sudden cardiac death.1 Intracardiac pacing studies can be performed in mice using a 1.1F octapolar catheter inserted into the jugular vein, and advanced into the right atrium and ventricle. Here, we illustrate the steps involved in performing programmed electrical stimulation in mice. Surface ECG and intracardiac electrograms are recorded simultaneously in the atria, atrioventricular junction, and ventricular myocardium, whereas intracardiac pacing of the atrium is performed using an external stimulator. Thus, programmed electrical stimulation in mice provides unique opportunities to explore molecular mechanisms underlying conduction defects and cardiac arrhythmias.

Programmed electrical stimulation provides the ability to determine conduction properties of the heart, and the possibility to induce and terminate cardiac arrhythmias using various pacing protocols. Using a transvenous catheter, intracardiac electrogram recordings can be obtained in mice following programmed electrical stimulation protocols to identify arrhythmogenic substrates.

程控电刺激小鼠

Genetically-modified mice have emerged as a preferable animal model to study the molecular mechanisms underlying conduction abnormalities, atrial and ...

科研

医学

Using Visual and Narrative Methods to Achieve Fair Process in Clinical Care

The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is respect for patient's values, preferences, and expressed needs. Yet specific approaches to gaining this understanding and translating it to quality care in the clinical setting are lacking. From a patient perspective quality is not a simple concept but is best understood in terms of five dimensions: technical outcomes; decision-making efficiency; amenities and convenience; information and emotional support; and overall patient satisfaction. Failure to consider quality from this five-pronged perspective results in a focus on medical outcomes, without considering the processes central to quality from the patient's perspective and vital to achieving good outcomes. In this paper, we argue for applying the concept of fair process in clinical settings. Fair process involves using a collaborative approach to exploring diagnostic issues and treatments with patients, explaining the rationale for decisions, setting expectations about roles and responsibilities, and implementing a core plan and ongoing evaluation. Fair process opens the door to bringing patient expertise into the clinical setting and the work of developing health care goals and strategies. This paper provides a step by step illustration of an innovative visual approach, called photovoice or photo-elicitation, to achieve fair process in clinical work with acquired brain injury survivors and others living with chronic health conditions. Applying this visual tool and methodology in the clinical setting will enhance patient-provider communication; engage patients as partners in identifying challenges, strengths, goals, and strategies; and support evaluation of progress over time. Asking patients to bring visuals of their lives into the clinical interaction can help to illuminate gaps in clinical knowledge, forge better therapeutic relationships with patients living with chronic conditions such as brain injury, and identify patient-centered goals and possibilities for healing. The process illustrated here can be used by clinicians, (primary care physicians, rehabilitation therapists, neurologists, neuropsychologists, psychologists, and others) working with people living with chronic conditions such as acquired brain injury, mental illness, physical disabilities, HIV/AIDS, substance abuse, or post-traumatic stress, and by leaders of support groups for the types of patients described above and their family members or caregivers.

This paper illustrates an innovative visual approach (photovoice or photo-elicitation) to achieve fair process in clinical care for patients living with chronic health conditions, illuminate gaps in clinical knowledge, forge better therapeutic relationships, and identify patient-centered goals and possibilities for healing.

利用视觉和叙事方法，以实现公平的进程中，在临床护理

The Institute of Medicine has targeted patient-centeredness as an important area of quality improvement. A major dimension of patient-centeredness is ...

A Murine Model of Muscle Training by Neuromuscular Electrical Stimulation

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional capacity. Transcutaneous surface stimulation of skeletal muscle involves a current flow between a cathode and an anode, thereby inducing excitement of the motor unit and the surrounding muscle fibers. 
NMES is an attractive modality to evaluate skeletal muscle adaptive responses for several reasons. First, it provides a reproducible experimental model in which physiological adaptations, such as myofiber hypertophy and muscle strengthening6, angiogenesis7-9, growth factor secretion9-11, and muscle precursor cell activation12 are well documented. Such physiological responses may be carefully titrated using different parameters of stimulation (for Cochrane review, see 13). In addition, NMES recruits motor units non-selectively, and in a spatially fixed and temporally synchronous manner14, offering the advantage of exerting a treatment effect on all fibers, regardless of fiber type. Although there are specified contraindications to NMES in clinical populations, including peripheral venous disorders or malignancy, for example, NMES is safe and feasible, even for those who are ill and/or bedridden and for populations in which rigorous exercise may be challenging. 
Here, we demonstrate the protocol for adapting commercially available electrodes and performing a NMES protocol using a murine model. This animal model has the advantage of utilizing a clinically available device and providing instant feedback regarding positioning of the electrode to elicit the desired muscle contractile effect. For the purpose of this manuscript, we will describe the protocol for muscle stimulation of the anterior compartment muscles of a mouse hindlimb.

A murine model of neuromuscular electrical stimulation (NMES), a safe and inexpensive clinical modality, to the anterior compartment muscles is described. This model has the advantage of modifying a readily available clinical device for the purpose of eliciting targeted and specific muscle contractions in mice.

一个小鼠模型，通过神经肌肉电刺激肌肉训练

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional ...

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 ...

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

Animal models are important tools to study the pathophysiology and pharmacology of neuropathic pain. This manuscript describes the surgical and behavioral procedures to study trigeminal neuropathic pain in rats. To meet the specificity of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is subjected to a chronic constriction injury (CCI) by loosely ligating the nerve. An intra-orbital approach is presented here to expose and ligate the IoN in the orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior and in response to von Frey hair stimulation that are indicative of persistent pain and mechanical allodynia. Two phases can be defined in the development of the behavioral changes. During the first week following IoN-CCI (phase 1), rats show an increased and asymmetric face grooming activity, i.e., with face wash strokes primarily directed to the nerve-injured IoN territory. A distinction is made between face grooming behavior that is part of a more general body grooming behavior, which remains largely unaffected by IoN-CCI, and face grooming that is neither preceded nor followed by body grooming, which is significantly increased after IoN-CCI. During this period, responsiveness to mechanical stimulation of the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an extreme hyperresponsiveness whereby even very weak stimulus intensities provoke nocifensive behavior (phase 2). The phenomenological similarities between these behavioral alterations and reported signs of facial pain (i.e., responses to noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia and mechanical allodynia in the ligated IoN territory.

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 ...

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. ...

Spontaneous and Evoked Measures of Pain in Murine Models of Monoarticular Knee Pain

Pain is the main cause of disability from arthritis. There is currently an unmet need for adequate treatments for arthritis pain. Pre-clinical models are necessary and useful for studying the mechanisms of pain and for evaluating efficacy of arthritis therapies. Measuring pain in animal models of arthritis is challenging. We have developed methods for measuring evoked and spontaneous pain in three models of murine arthritis. We quantitate the evoked pain responses of mice subjected to firm palpation of a painful knee. We also evaluate spontaneous pain by the proportion of weight and the amount of time placed on each of their 4 limbs after induction of arthritis pain in one knee. Joint pain in these mouse models produces a significant increase in evoked pain responses and an alteration in weight bearing. Since mice are quadrupeds, they offload the painful limb to the contralateral limb, to the forelimbs, or some combination. These methods are simple, require minimal equipment, and are reproducible and sensitive for detecting pain. They are useful for studying both disease-modifying arthritis treatments and analgesics in mice.

We have developed an evoked measure of arthritis pain and coupled it with a standardized method for measuring spontaneous pain in different murine models of chemically induced arthritis. These measures are sensitive and reproducible for different types of joint pain.

单关节膝关节疼痛小鼠模型疼痛的自发性和诱发性测量

Pain is the main cause of disability from arthritis. There is currently an unmet need for adequate treatments for arthritis pain. Pre-clinical models are ...

Updated Technique for Reliable, Easy, and Tolerated Transcranial Electrical Stimulation Including Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of brain stimulation presents several potential advantages compared to other techniques, as it is noninvasive, cost-effective, broadly deployable, and well-tolerated provided proper equipment and protocols are administered. Even though tDCS is apparently simple to perform, correct administration of the tDCS session, especially the electrode positioning and preparation, is vital for ensuring reproducibility and tolerability. The electrode positioning and preparation steps are traditionally also the most time consuming and error-prone. To address these challenges, modern tDCS techniques, using fixed-position headgear and pre-assembled sponge electrodes, reduce complexity and setup time while also ensuring that the electrodes are consistently placed as intended. These modern tDCS methods present advantages for research, clinic, and remote-supervised (at home) settings. This article provides a comprehensive step-by-step guide for administering a tDCS session using fixed-position headgear and pre-assembled sponge electrodes. This guide demonstrates tDCS using commonly applied montages intended for motor cortex and dorsolateral prefrontal cortex (DLPFC) stimulation. As described, selection of the head size and montage-specific headgear automates electrode positioning. Fully assembled pre-saturated snap-electrodes are simply affixed to the set position snap-connectors on the headgear. The modern tDCS method is shown to reduce setup time and reduce errors for both novice and expert operators. The methods outlined in this article can be adapted to different applications of tDCS as well as other forms of transcranial electrical stimulation (tES) such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). However, since tES is application specific, as appropriate, any methods recipe is customized to accommodate subject, indication, environment, and outcome specific features.

When administering transcranial direct current stimulation (tDCS), reproducible electrode preparation and placement are vital for a tolerated and effective session. The purpose of this article is to demonstrate updated modern setup procedures for the administration of tDCS and related transcranial electrical stimulation techniques, such as transcranial alternating current stimulation (tACS).

用于可靠、简单和耐受的颅内电刺激（包括颅内直流刺激）的更新技术

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of ...

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted&#160;quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The &#8220;working heart&#8221; measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.

This article presents an efficient method to perform myocardial ischemia and subsequent chronic reperfusion in rats using a minimally invasive approach. In addition, left ventricular hemodynamic function of rats is assessed by echocardiography and isolated working heart methods.&#160;

诱导大鼠心肌梗死的半微创方法及独立工作心脏系统对心脏功能的评估

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. 
Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. 
To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.

Partial sciatic nerve ligation induces long-lasting chronic neuropathic pain, characterized by exaggerated responses to thermal and mechanical stimuli. This mouse model of neuropathic pain is commonly used to study innovative therapies for pain management. This article describes in detail the surgical procedure to improve standardization and reproducibility.

部分坐骨神经结扎术:慢性神经性疼痛的小鼠模型，用于研究新疗法的抗伤害感受作用

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. ...