这项工作得到了比利时安特卫普大学医院 (UZA) 的多学科疼痛中心、麻醉学和危重护理医学部门的部门赠款的支持。此外, 还从安特卫普大学 (UA) 获得了一项教育补助金 (德豪斯 mandaat)。作者想感谢汤姆 Schepens 博士在修改本文时的专家帮助。

此单中心队列研究是根据 GCP 的道德标准和赫尔辛基宣言在比利时安特卫普大学医院的机构审查委员会和道德委员会批准后进行的 (研究标识符:16/33/334)。这项研究在 Clinicaltrials.gov (NCT02916004) 开始前注册。
所有包括的病人都是按照标准的医院镇静协议, 在学习报名前镇静剂。病人被滴定的里士满搅拌镇静秤 (RASS) 设置由 ICU 医生。患者在研究纳入 RASS 之前被镇静治疗4。所有患者例行滴定的行为疼痛量表 (BPS) 的3由 ICU analgosedation 协议。
注意: 不建议仅根据记录的疼痛反射的兴奋性来确定治疗措施。在解释测量时, 必须考虑反射弧的传出分支可能产生的影响。镇静或麻醉的患者比非镇静病人有更高的疼痛反射阈值。对于反射评估, 可能需要更高的电流。建议对生理参数 (心率、血压、呼吸率) 进行监测。
1. 安全防范措施
<ol><li>验证噪声控制的潜在混杂 (其他设备, 交替床垫)。</li>
	<li>验证环境温度是否在正常范围内。</li>
</ol>2. 主题的定位
<ol><li>将病人放置在床上, 保持臀部屈曲和膝部 130 160°的120°角。</li>
	<li>把手腕的手掌侧向上。</li>
	<li>确保非测量的眼睛在反射记录期间关闭。</li>
</ol>3. 制备电极用皮肤
注: 这将减少电极阻抗。
<ol><li>在应用场所修剪或剃毛。</li>
	<li>检查申请地点, 他们必须干净和干燥。如有必要, 用肥皂和水清洁皮肤, 用干洗布或纱布轻轻擦拭皮肤, 以去除任何身体乳液。</li>
	<li>擦伤使用可用磨料材料的应用现场。使用皮肤准备纸在一个大面积, 而不是只有一个单一的刷卡。</li>
	<li>在皮肤准备后立即应用每个电极。</li>
</ol>4. 电极的放置为瞳孔扩张反射 (民主共和国) 评估
注: 请参阅有关电极应用概述的数字。磁场和电场可能出现在测量轨迹中的背景噪声或其他文物。使用以下协议的最大可接受的噪声级别是从高于10µV 的值设置的. 在刺激之前区域的最大振幅 (即-130 ms 在刺激前达到-10 毫秒) 以上, 定义了高噪声水平, 超过了此可调阈值 ("最大可接受的噪音级别")。噪声值不被用来计算阈值, 刺激是重复的电流强度, 直到一个无噪音的肌电信号信号确定。要限制文物的发生, 请验证设备是否已更新到最新版本。可以通过最佳电极放置和皮肤准备来减少手工制品。
<ol><li>使用银 AgCl 电极与高导电性湿凝胶, 以确保最佳信号在反射记录。</li>
	<li>保持30毫米 (中心到中心) 之间的电极间距离。</li>
	<li>放置两个刺激电极为共和国录音, 在手腕上的皮肤区域支配的正中神经, 保持腕掌侧朝上向上。</li>
</ol>5. 电极的放置对伤害性屈曲反射 (NFR) 评估
注: 请参阅有关电极应用概述的数字。
<ol><li>在脚踝上使用两个刺激电极, 将电极置于侧踝远端, 刺激腓肠神经区。</li>
	<li>使用两个注册电极的肌电信号记录在股二头肌肌肉。将电极四指宽度在腘窝上方, 后侧到髂胫束带上。</li>
	<li>使用一个参考电极, 放置在四头肌肌腱。</li>
</ol>6. 安全检查
<ol><li>识别材料: 电池状态 (民主共和国工具), 附近的插头连接 (NFR 评估监视器) 的可访问性, 导线, 以及与标签设备插座的连接。</li>
	<li>识别病人: 病人数量, 病史, 当前药物, 行为疼痛量表, 镇静深度。</li>
</ol>7. 瞳孔扩张反射评估: 入门
<ol><li>将引线连接到手腕上的刺激电极上。验证黑色标记部件是否连接到最远端电极。</li>
	<li>打开红外线摄像机。</li>
	<li>选择测量协议: "瞳孔疼痛指数" (PPI), 通过菜单选择触摸屏显示。执行由有色符号指示的阻抗控制, 如有必要, 重复准备过程。</li>
	<li>用清水清洁照相机和眼睛驾驶室, 并对其进行消毒。</li>
</ol>8. 瞳孔扩张反射评估: 安装
<ol><li>打开眼睑, 将相机置于最佳位置。<ol>
<li>让橡胶眼罩在轨道上休息, 包围整个眼睛。</li>
		<li>验证是否正确设置了瞳孔检测并在必要时调整照相机。操作者可能需要提高眼睑。</li>
		<li>中心的瞳孔在屏幕中间, 并通过追求一个完全有色绿色的瞳孔来验证位置。</li>
	</ol>
</li>
	<li>关闭对侧眼睛, 减少一致的光反应。</li>
	<li>等待至少5秒钟开始测量, 确保学生住宿所需的稳定期 (暗测量环境)。</li>
</ol>9. 瞳孔扩张反射评估: 测量
<ol><li>按下触发器按钮开始测试。按住按钮直到瞳孔评估完成 (几秒钟)。确保整个测量周期由2个可听到的信号执行 (首先在开始时, 第二次测试结束时)<ol>
<li>测量时请勿移动摄像机;当刺激强度从10毫安增加到最大60毫安时, 屏幕上会显示倒计时。</li>
	</ol>
</li>
	<li>识别屏幕上15秒后自动显示的结果 基线瞳孔大小 (毫米) 在有害刺激之前 (黄色水平线)。 最大瞳孔大小 (毫米) 在有害刺激 (白色水平线) 以后。 不同级别的有害刺激的颜色带和价值。 最大瞳孔变异 (% 和毫米)。 PPI 评分</li>
	<li>在瞳孔评估后按下图标保存测量结果。</li>
</ol>10. 伤害屈曲反射评估: 入门
<ol><li>连接导线以进行刺激、记录和参考。验证黑色标记部件是否附着在最远端电极上;白色用于记录膝部的参考值。</li>
	<li>连接到电源时打开设备。如果需要数据存储, 请标识 USB 闪存驱动器。</li>
</ol>11. 伤害屈曲反射评估: 安装
<ol><li>按 "设置" 按钮转到 "配置" 菜单, 以验证在无意识镇静病人中反射测量的刺激设置和阈值确定程序。<ol>
<li>验证测量技术在阈值跟踪中。</li>
		<li>验证刺激类型是否确定为RIII 反射。</li>
		<li>当要求卢比输入时, 请选择 "关闭"。</li>
		<li>选择Z 峰值评分作为评价标准。</li>
		<li>使用 > 100 的刺激次数。</li>
		<li>启动刺激的强度为1毫安, 最小和最大步长为0.5 毫安。</li>
		<li>验证Interstimulus 间隔定义为8秒,反射范围为 90-180 毫秒。</li>
	</ol>
</li>
</ol>12. 伤害屈曲反射评估: 测量
<ol><li>开始测量,即自动反射阈值跟踪。</li>
	<li>通过重复皮肤准备协议, 在 "高噪声水平" 出现时减少阻抗。</li>
	<li>识别反射特征。<ol>
<li>确定应用于患者的电流和刺激的数量。</li>
		<li>通过大腿肌电图电极的刺激, 识别出200毫秒前显示的原始肌电图 300 ms。</li>
		<li>识别反射范围和反射阈值。参数以数字显示 (mA 中的值)。</li>
	</ol>
</li>
</ol>

作者没有什么可透露的。

本文介绍了两种伤害性反射装置在成人 ICU 患者客观 (患者独立) 疼痛评估中的应用。此外, 还介绍了 NFR 的评价和特征。
疼痛和谵妄在住院病人中很常见, 通常是结合在一起, 可能会对结果参数产生不利影响。在 ICU, 阿片类药物经常被管理, 有时与其他镇静剂结合, 以保护病人免受压力刺激, 如护理或各种诊断或治疗程序, 并改善机械通气治疗, 或他们可能是必要的, 因为严重的疾...

重症监护病房 (ICU) 中的许多危重病人在日常护理或诊断或治疗过程中往往会遇到疼痛。不符合标准的伤害评估和随后的次优疼痛管理可能会增加压力和焦虑1。持续性疼痛不仅增加循环儿茶酚胺, 损害组织灌注和减少氧传递2 , 但也激活代谢高代谢, 从而导致高血糖, 脂肪和肌肉损失。所有这些因素都损害了愈合过程, 并增加了感染的风险3,4,5,6。
正如国际疼痛研究协会 (IASP) 所指出的, 临床医生必须使用对所有患者都有效的疼痛评估工具, 自我报告仍然是疼痛评估的黄金标准。然而, 有许多情况下, 病人无法沟通, 特别是由于严重的疾病或当他们是机械通气 (MV)。随着对 ICU 患者相关结局措施的兴趣增加, 在病人无法报告疼痛和不适时, 需要有结构可靠的伤害性评估技术。由于缺乏具体、可重复和可行的监测工具, 解决这一需要的努力受到阻碍。近年来, 为医生提供更客观的伤害参数, 已有相当大的努力。然而, 在 ICU 中执行的许多研究都集中在使用生命体征作为疼痛评估的可能替代因素, 而不使用血压或心率作为疼痛7、8的具体参数。
正如先前的研究报告所报道的, 未经治疗的疼痛会严重损害患者的预后, 因此, 应始终独立评估生命体征, 评估不应受患者无法沟通7的影响, 8,9,10,11,12。由于疼痛已知的负面后果, 这种客观伤害评估方法得到了相当大的支持。特别是在 ICU 患者中, 生理和心理的影响可以是可观的和长期的, 可能会显著降低健康相关的生活质量13,14。
目前, 尚无客观的疼痛监测协议, 可以很容易地应用于一大群危重病患者。在 ICU 患者中实施客观评估工具, 可以优化疼痛管理, 防止中枢性敏化综合征的发展。此外, 阿片诱导的痛觉 (OIH), chronification 疼痛和长期疼痛相关的发病率可能会下降。最后, 应用伤害性反射评估工具可以提供一个独特的翻译平台, 新的药理镇痛化合物可以测试。
拟议方法的目的是提供技术要求的概览, 并详细说明用于评估非交际性 ICU 患者的伤害性反应的议定书。总的来说, 我们的目的是为在 ICU 和在其他情况下, 需要评估镇静剂或无意识的病人, 提供一个全面的指南, 以使用客观的疼痛测量工具。
从2016年10月到 2017年12月, 被纳入 ICU 的危重昏迷成人被筛选为研究对象。所有机械通气, 并接受了严格的 analgosedation 协议, 含有异丙酚/瑞芬太尼或异丙酚/舒芬太尼, 这是两个最常用的方案在我院。眼科手术病史, 已知瞳孔反射障碍, 霍纳或阿迪综合征, 前眼外伤, 颅神经损伤或急性颅内高压引起的颅脑损伤, 肿瘤压迫或出血, 暴发性中风,已知 (聚) 神经病变与糖尿病或其他神经疾病相关, 已知影响反射活动, 内或体外治疗 (起搏器, 主动脉内球囊泵, 体外生命支持), 慢性阿片类药物使用 (> 3 月), 年龄< 18 年来, 使用局部干扰眼药水 (阿托品, 肾上腺素), α2肾上腺素激动剂15, 使用其他 analgosedation 协议比描述的纳入标准或神经肌肉阻滞药被定义为排除标准。
从数字病人数据管理系统 (例如, Metavision) 提取了注册科目的人口统计学变量和医学数据, 包括简化的急性生理学评分 ii (sap ii),16 。
疼痛评估
ICU 患者被筛选为研究纳入, 这需要一个病史和入院诊断, 以评估纳入和排除标准上述。在现实生活条件下, 在 ICU 环境中评估生理反应: 没有对温度或噪声控制进行具体的修改。反射评估在日间工作时间在大约20°c 的单独患者房间执行了。当在触摸屏显示器上启用此功能时, 所有生成的数据 (反射特性) 都可以存储在两个设备中。
瞳孔扩张反射的测量
采用红外视频记录法对瞳孔扩张反射 (pupillometry) 进行定量瞳孔大小评价。对于标准伤害刺激的应用, 两个低阻抗的银 AgCl 电极被放置在皮肤区域支配由正中神经在左侧手臂后, 皮肤准备 (图 1)。电流固定在 60 milliampères (mA), 最大可接受电阻为5欧姆, 定义电压限制为300伏特 (V)。
通过内置的瞳孔疼痛指数 (PPI) 测量协议, 为动态瞳孔反射评估生成自动电刺激模式, 进行了民主评估。标准化的有害刺激被应用了以增加的强度 (从 10 ma 到 60 ma 以增量步 10 ma, 期间 1 s 和脉宽200µs) 直到瞳孔膨胀大于 13% ([最大直径最小直径]/最大直径 * 100) 或最大刺激 60 mA 达到。当达到定义的标准时, 刺激被自动中断, 并显示 PPI 评分 (表 1)。基线瞳孔大小 (标准的有害刺激之前), 瞳孔反射幅度 (PRA), 刺激强度和 PPI 评分记录。根据所需刺激的数量, 民主共和国的测量时间为2至16秒。
一些研究表明, pupillometry 在非交际性 ICU 成人中的应用。保卢斯等人表明, 民主评估可能预测的镇痛要求在气管吸入17。此外, 这种方法可能能够揭示不同程度的镇痛, 并可能有歧视性的性质, 对不同类型的有害程序18,19。最近, 由于其低刺激电流, 科学上的兴趣已经转向使用特定的《民主共和国评估议定书》。我们的方法中建议的 PPI 协议以前曾在麻醉成人中进行过调查, 揭示了民主共和国与阿片管理20之间的显著相关性。此外, Sabourdin等。21表明, 可用于指导个别术中瑞芬太尼的管理, 从而减少术中阿片的消耗和术后抢救镇痛的要求。
痛觉屈曲反射的测量
为了评估初级传入纤维在痛觉受器外周向交感神经链中的伤害信号传输中的作用, 评估了伤害性屈曲反射 (NFR)。反射诱导是介导的一个三角洲纤维被激活后, 神经元之间的复杂相互作用位于脊髓背角的22。Rhudy 和同事们描述了 RIII 反射, NFR 在 nociceptor 激活后, 以高阈值伤害性特征测量 electromyographically (肌电图) 的晚期反应。23
增加电刺激是通过皮肤银 AgCl 电极在侧踝, 触发单一感觉腓肠神经。通过肌电信号记录的时间和振幅来评估反射响应 (图 2;经博士批准转载. 1月 Baars, 董事总经理, Dolosys 有限公司。
跟随冷漠等, 使用描述的反射注册设置, 需要刺激强度引出 NFR (阈值跟踪) 可以作为一个客观伤害评估相关的主观疼痛评分24,25,26,27,28. 随后, 已进行了大量研究, 以确定反射性特征 (主要是反射阈值和振幅) 及其与有意识成人疼痛强度感觉的相关性。这些研究表明, 反射阈值和反应振幅与疼痛强度27、29、30密切相关。此外, 标准的 NFR 评分标准, 如反射峰和平均反射肌电图活动, 可作为可靠的标准, 以确定这 NFR23,31,32。根据最近的研究, 所定义的反射特性贡献的 NFR, 尽管他们的经验来源, 显示良好的测试重测信度33,34。NFR 记录的持续时间, 考虑到 (可变) 步长范围 (0.5 毫安-2 ma), interstimulus 间隔8秒, 间隔随机化 20%, 以避免在刺激90后 180-35 毫秒之间可能的适应和反射范围, 是在5和15分钟之间取决于必要的刺激强度, 以引出 NFR, 因此, 所需刺激性的数量 (最多 100 mA)。

<table><tbody><tr><td>Neurolight Algiscan</td><td>ID Med, Marseille, France&amp;nbsp;</td><td>Pupillometre 13235</td><td>Infra red camera for pupil dilation reflex measurement</td></tr><tr><td>Paintracker</td><td>Dolosys GmbH, Belin, Germany</td><td>Paintracker V1 2497</td><td>Nociception flexion reflex assessment tool</td></tr><tr><td>Red DotTrace Prep</td><td>3M, Ontario, Canada</td><td>CV-0001-7353-0</td><td>Skin surface preparation tape</td></tr><tr><td>Electrodes - BlueSensor N</td><td>Ambu, Ballerup, Denmark</td><td>BlueSensor N N-00-S/25&amp;nbsp;</td><td>Low-impedance Ag-AgCl skin electrodes</td></tr></tbody></table>

objective nociceptive assessment in ventilated icu patients: a feasibility study using pupillometry and the nociceptive flexion reflex

客观伤害评估和最佳疼痛管理的概念得到了越来越多的关注。尽管已知的疼痛或过度 analgosedation 的负面短期和长期后果, 但在非交际性的、危重的成年人中, 充分的伤害性监测仍然具有挑战性。重症监护病房 (ICU) 采用机械通气患者的行为疼痛量表 (BPS) 对护理人员进行常规伤害评估。这种评估受药物使用的限制 (例如,神经肌肉阻断剂) 和第三方伤害评估固有的主观特征。
在这里, 我们描述了使用两个伤害性反射测试设备作为工具, 客观的疼痛评估: 瞳孔扩张反射 (民主) 和伤害屈曲反射 (NFR)。这些测量工具是非侵入性和良好耐受性, 为临床医生和研究人员提供了关于两种不同伤害处理途径的客观信息: (1) 与疼痛相关的自主反应性和 (2) 体感系统的提升分量。目前, 使用共和国和 NFR 测量仅限于专门的疼痛诊所和研究机构, 因为这些印象表明, 这些技术要求很高或耗时, 甚至是因为缺乏对其存在。
本文通过对上述两种伤害性反射评估的研究, 评价其作为一种生理疼痛测量方法在日常实践中的可行性。采用新的技术来评估无意识患者的镇痛水平, 可以进一步改善个体的药理治疗和患者相关的结局指标。因此, 未来的研究必须包括在现实生活环境中进行的大型精心设计的临床试验。

我们使用先前描述的议定书, 在 ICU 部门总共用了40个严重不适通气对象 (38% 名女性) 进行反射评估。analgo 镇静的患者包括: 58% 为原发性呼吸功能不全, 23% 由于多器官衰竭, 10% 的患者有感染性休克, 9% 被定义为其他原因的镇静剂 (例如,心源性原因)。所有测量都由同一调查员执行。镇静剂剂量在评估期间从未被调整过。瞳孔特征和肌电图反应见表 2。
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Watch this Scientific Journal Video about Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex at JoVE.com

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

尽管开发了创新的客观疼痛评估工具, 但在麻醉病人中无法以任何方式与外界交流的疼痛评估仍然具有挑战性。本项目对危重、机械通气的成人患者进行瞳孔扩张反射和伤害屈曲反射的评估。

应用 Pupillometry 和伤害性屈曲反射的可行性研究--通气 ICU 患者的客观伤害评估

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and ...

objective-nociceptive-assessment-ventilated-icu-patients-feasibility

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SCIENTISTS IN ACTION

8.7K 次观看.  Antwerp University Hospital (UZA), University of Antwerp (UA). 尽管开发了创新的客观疼痛评估工具, 但在麻醉病人中无法以任何方式与外界交流的疼痛评估仍然具有挑战性。本项目对危重、机械通气的成人患者进行瞳孔扩张反射和伤害屈曲反射的评估。

视频: Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

An Experimental Paradigm for the Prediction of Post-Operative Pain (PPOP)

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in S&atilde;o Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery.
A significant number of women experience moderate or severe acute post-partum pain after vaginal and cesarean deliveries. 1 Furthermore, 10-15% of women suffer chronic persistent pain after cesarean section. 2 With constant increase in cesarean rates in the US 3 and the already high rate in Brazil, this is bound to create a significant public health problem. When questioning women's fears and expectations from cesarean section, pain during and after it is their greatest concern. 4 Individual variability in severity of pain after vaginal or operative delivery is influenced by multiple factors including sensitivity to pain, psychological factors, age, and genetics. The unique birth experience leads to unpredictable requirements for analgesics, from 'none at all' to 'very high' doses of pain medication. Pain after cesarean section is an excellent model to study post-operative pain because it is performed on otherwise young and healthy women. Therefore, it is recommended to attenuate the pain during the acute phase because this may lead to chronic pain disorders. The impact of developing persistent pain is immense, since it may impair not only the ability of women to care for their child in the immediate postpartum period, but also their own well being for a long period of time.
In a series of projects, an international research network is currently investigating the effect of pregnancy on pain modulation and ways to predict who will suffer acute severe pain and potentially chronic pain, by using simple pain tests and questionnaires in combination with genetic analysis. A relatively recent approach to investigate pain modulation is via the psychophysical measure of Diffuse Noxious Inhibitory Control (DNIC). This pain-modulating process is the neurophysiological basis for the well-known phenomenon of 'pain inhibits pain' from remote areas of the body. The DNIC paradigm has evolved recently into a clinical tool and simple test and has been shown to be a predictor of post-operative pain.5 Since pregnancy is associated with decreased pain sensitivity and/or enhanced processes of pain modulation, using tests that investigate pain modulation should provide a better understanding of the pathways involved with pregnancy-induced analgesia and may help predict pain outcomes during labor and delivery. For those women delivering by cesarean section, a DNIC test performed prior to surgery along with psychosocial questionnaires and genetic tests should enable one to identify women prone to suffer severe post-cesarean pain and persistent pain. These clinical tests should allow anesthesiologists to offer not only personalized medicine to women with the promise to improve well-being and satisfaction, but also a reduction in the overall cost of perioperative and long term care due to pain and suffering. On a larger scale, these tests that explore pain modulation may become bedside screening tests to predict the development of pain disorders following surgery.

An Experimental Paradigm for the Prediction of Post-Operative Pain PPOP

Diffuse noxious inhibitory control, temporal summation and wound hyperalgesia testing are demonstrated in the obstetric patient. These tests evaluate inhibitory and excitatory mechanisms of pain processing and are here utilized to evaluate endogenous analgesia at different time-points during pregnancy and the peripartum period to help reveal individual s risk for persistent pain.

用于预测手术后的疼痛的实验范式（PPOP）

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative ...

科研

医学

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 ...

行为学

Meal Duration as a Measure of Orofacial Nociceptive Responses in Rodents

A lengthening in meal duration can be used to measure an increase in orofacial mechanical hyperalgesia having similarities to the guarding behavior of humans with orofacial pain. To measure meal duration unrestrained rats are continuously kept in sound attenuated, computerized feeding modules for days to weeks to record feeding behavior. These sound-attenuated chambers are equipped with chow pellet dispensers. The dispenser has a pellet trough with a photobeam placed at the bottom of the trough and when a rodent removes a pellet from the feeder trough this beam is no longer blocked, signaling the computer to drop another pellet. The computer records the date and time when the pellets were taken from the trough and from this data the experimenter can calculate the meal parameters. When calculating meal parameters a meal was defined based on previous work and was set at 10 min (in other words when the animal does not eat for 10 min that would be the end of the animal&#39;s meal) also the minimum meal size was set at 3 pellets. The meal duration, meal number, food intake, meal size and inter-meal interval can then be calculated by the software for any time period that the operator desires. Of the feeding parameters that can be calculated meal duration has been shown to be a continuous noninvasive biological marker of orofacial nociception in male rats and mice and female rats. Meal duration measurements are quantitative, require no training or animal manipulation, require cortical participation, and do not compete with other experimentally induced behaviors. These factors distinguish this assay from other operant or reflex methods for recording orofacial nociception.

A lengthening in meal duration represents orofacial nociceptive behavior in rodents similar to the guarding behavior of humans with orofacial pain. Eating is a behavior that requires no training or animal manipulation, requires cortical participation, and is not competing with other experimentally induced behaviors, distinguishing this assay from alternative reflex or operant measurements.

膳食持续时间作为衡量啮齿动物的奥体非感知反应的指标

A lengthening in meal duration can be used to measure an increase in orofacial mechanical hyperalgesia having similarities to the guarding behavior of ...

Quantitative Assessment of Cortical Auditory-tactile Processing in Children with Disabilities

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess children&#39;s cortical processing of light touch, speech sounds and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing children discomfort. To accomplish this we developed a dual channel, time and strength calibrated air puff stimulator that allows both tactile stimulation and sham control. We combined this with the use of event-related potential methodology to allow for high temporal resolution of signals from the primary and secondary somatosensory cortices as well as higher order processing. This methodology also allowed us to measure a multisensory response to auditory-tactile stimulation.

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology to quantitatively assess infants and children&#39;s cortical processing of light touch, speech sounds, and the multisensory processing of the 2 stimuli, without requiring active subject participation or causing discomfort in vulnerable patients.

皮质听觉，触觉加工的残疾儿童定量评价

Objective and easy measurement of sensory processing is extremely difficult in nonverbal or vulnerable pediatric patients. We developed a new methodology ...

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs. Additionally, available testing methods could not be implemented acutely or when severe motor impairments existed, preventing studies of the development of SCI-induced allodynia3. Here we present two validated sensory testing methods using von Frey Hair (VFH) monofilaments which quantify changes in tactile sensory thresholds after SCI4-5. One test is the well-established Up-Down test which demonstrates high sensitivity and specificity across different SCI severities when tested chronically5. The other test is a newly-developed dorsal VFH test that can be applied acutely after SCI when allodynia develops, prior to motor recovery4-5. Each VFH monofilament applies a calibrated force when touched to the skin of the hind paw until it bends. In the up-down method, alternating VFHs of higher or lower forces are used on the plantar L5 dermatome to delineate flexor withdrawal thresholds. Successively higher forces are applied until withdrawal occurs then lower force VFHs are used until withdrawal ceases. The tactile threshold reflects the force required to elicit withdrawal in 50% of the stimuli. For the new test, each VFH is applied to the dorsal L5 dermatome of the paw while the rat is supported by the examiner. The VFH stimulation occurs in ascending order of force until at least 2 of 3 applications at a given force produces paw withdrawal. Tactile sensory threshold is the lowest force to elicit withdrawal 66% of the time. Acclimation, testing and scoring procedures are described. Aberrant trials that require a retest and typical trials are defined. Animal use was approved by Ohio State University Animal Care and Use Committee.

We describe two tactile sensory testing methods for acute or chronic periods of spinal cord injury in rats. These validated procedures can detect the development and maintenance of allodynia-like sensations.

在大鼠脊髓损伤后的急性和慢性触觉测试

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task&#160;battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.

Human pain models are valuable tools used to assess the analgesic potential of novel compounds and predict their clinical efficacy, especially when used in an integrated manner. Although implementation of these models is complex, with proper execution, the pain models described in this protocol can provide predictive and reliable results.

确定疼痛的检测和容忍阈值使用集成的，多模式疼痛任务电池

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify ...

Electrophysiological Measurements and Analysis of Nociception in Human Infants

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns.
The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord.
This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.

The assessment and treatment of pain in infants is difficult because infants cannot verbally report their experience. In this video we describe quantitative electrophysiological methods and analysis techniques that can be used to measure the response to noxious events from the infant nervous system.

在人类婴儿的伤害性电生理测量和分析

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are ...

神经科学

Pupillary Response as Assessment of Effective Seizure Induction by Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is reported to be effective for severe neuropsychiatric disorders. In ECT, electrical stimulation is applied to the brain, inducing seizure activity. Adequate seizure induction with ECT is associated with seizure duration, symmetrical high amplitude waveforms during slow-wave activity, postictal suppression, and activation of the sympathetic nervous system. Sympathetic nervous system activation is influenced by anesthetic agents or cardiovascular drugs during ECT. Pupillary responses can reflect sympathetic nervous activity or the degree of brain damage. Pupillary response measurement can be conducted in a simple, precise, and objective way using an automated infrared pupillometer, enabling the measurement of pupil diameter (mm) to two decimal places. The white light used for measuring light reflexes is not overly bright, and patients do not typically report discomfort. Pupillary light reflexes were measured before anesthesia induction and immediately after electrical stimulation using this equipment. Pupil diameter is typically enlarged after brain damage or sympathetic nervous activation. Adequate seizure induction using ECT could induce pupillary enlargement immediately after electrical stimulation. In the current method, the constriction ratio of pupil size was calculated automatically and compared with seizure quality. Pupillary responses immediately after electrical stimulation may provide a useful assessment of the efficacy of seizure induction with ECT.

Pupillary responses (light reflex) were measured for assessment of adequate seizure induction by electroconvulsive therapy using an automated infrared pupillometer immediately after electrical stimulation. Constriction ratio was calculated and compared with seizure quality.

电惊厥治疗有效癫痫发作诱导的瞳孔反应评估

Electroconvulsive therapy (ECT) is reported to be effective for severe neuropsychiatric disorders. In ECT, electrical stimulation is applied to the brain, ...

Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay

Pain has sensory and affective components. Unlike traditional, reflex-based pain assays, operant pain assays can produce more clinically relevant results by addressing the cognitive and motivational aspects of pain in rodents. This paper presents a protocol for assessing mechanical hypersensitivity following chronic constriction injury of the infraorbital nerves (CCI-ION) in rats using an orofacial operant pain system. Before CCI-ION surgery, rats were trained in an orofacial pain assessment device (OPAD) to drink sweetened condensed milk while making facial contact with the metal spiked bars and lick-tube.
In this assay, rats can choose between receiving milk as a positive reinforcer or escaping an aversive mechanical stimulus that is produced by a vertical row of small pyramid-shaped spikes on each side of the reward access hole. Following 2 weeks of training in the OPAD and before the CCI-ION surgery, baseline mechanical sensitivity data were recorded for 5 days for each rat during a 10 min testing session. During a session, the operant system automatically records the number of reward bottle activations (licks) and facial contacts, contact duration, and latency to the first lick, among other measures.
Following baseline measurements, rats underwent either CCI-ION or sham surgery. In this protocol, mechanical hypersensitivity was quantified by measuring the number of licks, latency to the first lick, the number of contacts, and the ratio of licks to facial contacts (L/F). The data showed that CCI-ION resulted in a significant decrease in the number of licks and the L/F ratio and an increase in the latency to the first lick, indicating mechanical hypersensitivity. These data support the use of operant-based pain assays to assess mechanical pain sensitivity in preclinical pain research.

This protocol describes the assessment of mechanical hypersensitivity in a rat model of neuropathic orofacial pain using an operant-based orofacial pain assessment device.

使用口面部操作性疼痛测定法评估大鼠神经损伤诱导的机械超敏反应

Pain has sensory and affective components. Unlike traditional, reflex-based pain assays, operant pain assays can produce more clinically relevant results ...

Electrophysiological Measurement of Noxious-evoked Brain Activity in Neonates Using a Flat-tip Probe Coupled to Electroencephalography

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. Those tools are subjective or determine secondary physiological indicators which also have certain limitations particularly when exploring the effectiveness of analgesia. As cortical processing is essential for pain perception, brain activity measures may provide a useful approach to assess pain in infants. Here we present a method to assess nociception with electrophysiological brain activity recordings optimized for the use in newborn infants. To produce highly standardized and reproducible noxious stimuli we applied mechanical stimulation with a flat-tip probe, e.g., PinPrick, which is not skin-breaking and does not cause behavioral distress. The noxious-evoked potential allows the objective measurement of nociception in non-verbal patients. This method can be used in newborn infants as early as 34 weeks of gestational age. Moreover, it could be applied in different situations such as measuring the efficacy of analgesic or anesthetic drugs.

Measuring pain in non-verbal patients is a challenge. In this study we combine EEG recording with stimulation using a flat-tip probe to detect noxious-evoked brain activity in an objective manner.

应用平板探针结合脑电图对新生儿有害诱发脑活动的电生理测量

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. ...