我们感谢参加 "代表性成果" 部分的研究的病人。

这项议定书已在先前的随机对照试验中得到批准, 由荷兰的人类研究伦理委员会区域奈梅亨 (2004/239).
1. 测试准备
<ol><li>
知情同意:
	<ol>
<li>与患者一起复查知情同意表。</li>
		<li>回答病人可能对研究的任何问题。</li>
		<li>通过让病人签署知情同意书并亲自签署, 获得书面知情同意。</li>
	</ol>
</li>
	<li>
测试环境:
	<ol>
<li>在协议中执行所有的测量, 在一个刺激穷人和温度稳定环境 (〜21° c, 没有音乐, 没有被发现的窗口, 电话关闭)。 注意: 实验者的衣物必须尽可能中性, 即穿上实验室外衣, 在肘部下方赤裸, 不要佩戴首饰, 也不要佩戴香水。众所周知, 实验者相关因素可能对测量结果有影响。其中一些因素并非完全 standardizable (例如性), 但在准备测量的性能时应牢记这一点。</li>
		<li>在测量期间, 确保病人和研究员是唯一的人在房间里, 要求别人离开。</li>
		<li>将 "请勿打扰" 标志贴在门上, 以免在测量过程中受到干扰。</li>
		<li>与病人在床上的仰卧位进行所有的测试, 除了 CPM 测试, 这是与病人的坐姿。</li>
	</ol>
</li>
	<li>
测试站点:
	<ol>
<li>使用外科皮肤标记标记以下站点进行阈值测试: 在双肩 (C5 dermatome, 压力和电阈值) 下的大结节下的区域, 双边鱼际 (C6, dermatome, 压力), 双边髂嵴 (L1 dermatome, 压力和电), 双边在中期腋窝线乳癌手术切口的乳房高度或7厘米 (T4 dermatome, 压力和电阈值)。</li>
		<li>使用外科皮肤标记标记 CPM 测试站点:15 厘米以上的非显性身体部位的髌骨 (L3 dermatome, 压力)。</li>
		<li>使用外科皮肤标记标记一个测试运行站点, 例如, 在占主导地位的身体部位的髌骨上方15厘米。</li>
	</ol>
</li>
	<li>
电刺激配置:
	<ol>
<li>在每个电刺激试验场上的标记点的两侧涂抹两个自粘的皮肤电极。将电极放在它们的外径上, 这样它们就会在有标记的地方互相接触。</li>
		<li>设置 QST 刺激器提供强直刺激 (100 赫兹, 0.2 ms 方波)-图 1。将爬坡率设置为1毫安. 将初始电流设置为0毫安, 最大电流自动设置为50毫安, 以达到安全目的。</li>
	</ol>
</li>
</ol>2. 电痛阈值
<ol><li>
电力输送:
	<ol>
<li>使用 QST 刺激器。使用连接引线将自粘电极连接到刺激器。</li>
	</ol>
</li>
	<li>
视觉模拟量表 (VAS) 的测量:
	<ol>
<li>使用连接到 QST 刺激器的 vas 滑块获得 vas 分数。vas 滑块由一个表示 vas 的水平条上的移动拉杆组成的盒子构成。把滑块递给病人。</li>
		<li>向病人解释如何使用滑块: "控制单元有一个滑块。这个滑块可以移动, 以表明你如何体验刺激的规模, 不痛苦的最坏想象的痛苦.
</li>
	</ol>
</li>
	<li>测试运行:<ol>
<li>向患者解释电检测阈值 (EDT) 的过程: "我们将进行测试, 让您熟悉测量。刺激将开始时, 你按下按钮, 将逐渐增加, 并会立即停止后, 松开按钮。请按按钮, 当我告诉你这样做, 并放手时, 你有什么感觉. 注意: 所有指令都从手册中读取, 以帮助标准化。</li>
		<li>在测试运行站点上执行单个测试运行以演示过程。在测量表上记录结果-图 2。确保患者在执行测试时不能读取测量值。</li>
		<li>请病人用 VAS 滑块来说明他/她是如何经历刺激的, 并记下结果。</li>
		<li>解释的程序为电气疼痛阈值 (EPT) 病人: "我们将进行测试运行, 让您熟悉的测量。这项测试的目的是确定你的疼痛知觉响应电刺激。刺激将开始时, 你按下按钮, 将逐渐增加, 并会立即停止后, 松开按钮。当我告诉你这样做时, 请按下按钮, 当刺激变得痛苦的时候放手.
</li>
		<li>在测试站点上执行单个测试运行以演示过程。在测量表上记录结果。</li>
		<li>请病人用 VAS 滑块来说明他/她是如何经历刺激的, 并记下结果。</li>
	</ol>
</li>
	<li>
测量:
	<ol>
<li>使用2.3.1 的措辞, 再次向患者解释 EDT 的程序。</li>
		<li>测量在不同的研究地点的 EDT (首先 C5, 然后 T4, 然后 L1)。在每个测量站点执行 EDT 测量三次, 允许在测量之间至少15秒, 以避免饱和的影响。</li>
		<li>在每个站点的最后一次 EDT 测量后, 要求患者对 VAS 的相关疼痛进行评分。注意测量表上的电值和 VAS 分数。确保患者在执行测试时不能读取测量值。</li>
		<li>解释的程序, 以确定 EPT 再次使用的措辞从2.3.4。</li>
		<li>在不同的研究地点测量 EPT (先是 C5, 然后是 T4, 然后是 L1)。在每个测量站点执行 EPT 测量三次, 允许在测量之间至少15秒, 以避免饱和效果。</li>
		<li>在每个部位的最后一次 EPT 测量后, 要求患者对 VAS 的相关疼痛进行评分。</li>
		<li>注意测试测量表上的电值和 VAS 分数。确保患者在执行测试时不能读取测量值。</li>
	</ol>
</li>
</ol>3. 压力痛阈值
<ol><li>
交货压力:
	<ol>
<li>交付压力与压力 algometer 与 1.0 cm2探针在90°角度之下。通过手动调整施加的压力和显示器上的压力, 使用5米/秒的斜向速度。从 0 n 开始, 并申请最多 200 n 的安全目的。 注意: 小心不要让设备滑到皮肤上。为了防止 algometer 的打滑, 重要的是将探头垂直于皮肤, 并在缓慢增加压力的同时, 用双手支撑 algometer。研究人员应坚定地站出来, 以提供控制的压力增加。</li>
	</ol>
</li>
	<li>
测试运行:
	<ol>
<li>向病人解释程序: "我们将进行一个测试运行, 让您熟悉测量。这项测量的目的是确定你的感觉肌肉的压力疼痛。我会在你的肌肉上放一个压力测量装置, 并会逐渐增加压力。当压力感觉变得悸动、燃烧或痛苦时, 请告诉我 ' 现在 '.
</li>
		<li>在测试站点上执行单个测试运行。确保患者在执行测试时不能读取测量值。在测量表上记录结果。</li>
	</ol>
</li>
	<li>
测量:
	<ol>
<li>重复使用3.2.1 的措辞的病人的说明。</li>
		<li>将压力施加到不同的学习地点 (先是 C5, 然后 C6, 然后 T4, 然后 L1)。在每个测量站点上执行两次压力痛阈值 (PPT) 测量, 在测量之间至少允许15秒, 以避免饱和效果。</li>
		<li>在每个站点的最后一次 PPT 测量后, 要求患者对 VAS 的相关疼痛进行评分。</li>
		<li>注意测试压力值和测量表上的 VAS 分数。</li>
	</ol>
</li>
</ol>4. 适应的痛苦调制范例
<ol><li>
预适应测试刺激
	<ol>
<li>重复3.1.1。但使用 PPT 作为测试刺激。重复使用3.2.1 的措辞的病人的说明。</li>
		<li>在 CPM 测试站点上测量预调节 PPT (m。股骨直肌(L3) 在非显性侧, 15 厘米以上的髌骨)。要求患者对 VAS 滑块的相关疼痛进行评分。注意压力变得疼痛的值和相关的疼痛评分。</li>
		<li>向病人解释冰水的过程: "这是一个测试, 以获得关于你的身体处理不同的疼痛信号的方式在同一时间的信息。我会请你把手 submerse 在水桶里的冰水里。把你的手放在水里, 直到手腕和手指张开。请握住你的手在冰水中, 直到你不能再容忍它.
</li>
		<li>告诉病人在浸泡3分钟后将手从水中移开, 或在疼痛变得无法忍受的情况下更快。每10秒, 我就会要求你把疼痛率定在0到10的范围内, 其中0表示没有疼痛和10的痛苦。在你把你的手从冰水中取出后, 我们会再次测量你腿部的压力痛阈值, 类似于我们以前的做法.
</li>
	</ol>
</li>
	<li>
调节刺激:
	<ol>
<li>使用冷升压任务作为调节刺激。使用温度探头测量水温, 并注意温度 (目标温度介于1° c 和4° c 之间)。</li>
		<li>让病人在冰冷的水中浸泡支配的手。要求患者每10秒在 VAS 时对整个冷压任务的疼痛进行评分, 并记下结果。注意测量表上完成的浸泡时间 (最长为180秒, 平均为56±五十五年代8)。</li>
	</ol>
</li>
	<li>
确定测试刺激后的调节:
	<ol>
<li>在调节刺激后, 在 CPM 测试站点上测量 PPT。要求患者对 vas 的相关疼痛进行评分, 并将 PPT 和 vas 评分记录在纸上。</li>
	</ol>
</li>
</ol>5. 计算
<ol><li>
EPTs:
	<ol>
<li>计算 EDTs 和 EPTs 的每个测试位置的平均值。</li>
	</ol>
</li>
	<li>
PPTs:
	<ol>
<li>计算 PPTs 的每个测试位置的平均值。</li>
	</ol>
</li>
	<li>
cpm:
	<ol>
<li>通过在调节刺激10前后的 cpm 测试位置计算 PPT 中的相对变化 (%) 来确定 cpm 效果。 CPM = (ppt帖子– pptpre/ppt前) * 100 有条件的疼痛调制;PPT = 压力痛阈值。</li>
	</ol>
</li>
</ol>

<ol>
	<li>Macrae, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+post-surgical+pain:+10+years+on.">Chronic post-surgical pain: 10 years on.</a> Br J Anaesth. 101 (1), 77-86 (2008).</li><li>IASP Taxonomy Working Group. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Classification of Chronic Pain. , (2011).</li><li>Kehlet, H., Jensen, T. S., Woolf, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+postsurgical+pain:+risk+factors+and+prevention.">Persistent postsurgical pain: risk factors and prevention.</a> Lancet. 367 (9522), 1618-1625 (2006).</li><li>Steegers, M. A., Wolters, B., Evers, A. W., Strobbe, L., Wilder-Smith, O. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+axillary+lymph+node+dissection+on+prevalence+and+intensity+of+chronic+and+phantom+pain+after+breast+cancer+surgery.">Effect of axillary lymph node dissection on prevalence and intensity of chronic and phantom pain after breast cancer surgery.</a> J Pain. 9 (9), 813-822 (2008).</li><li>Yarnitsky, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+of+chronic+post-operative+pain:+pre-operative+DNIC+testing+identifies+patients+at+risk.">Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.</a> Pain. 138 (1), 22-28 (2008).</li><li>Hsu, E., Cohen, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Postamputation+pain:+epidemiology,+mechanisms,+and+treatment.">Postamputation pain: epidemiology, mechanisms, and treatment.</a> J Pain Res. 6, 121-136 (2013).</li><li>Franneby, U., Sandblom, G., Nordin, P., Nyren, O., Gunnarsson, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+factors+for+long-term+pain+after+hernia+surgery.">Risk factors for long-term pain after hernia surgery.</a> Ann Surg. 244 (2), 212-219 (2006).</li><li>van Helmond, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperalgesia+and+Persistent+Pain+after+Breast+Cancer+Surgery:+A+Prospective+Randomized+Controlled+Trial+with+Perioperative+COX-2+Inhibition.">Hyperalgesia and Persistent Pain after Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition.</a> PLoS One. 11 (12), e0166601 (2016).</li><li>Le Bars, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+whole+body+receptive+field+of+dorsal+horn+multireceptive+neurones.">The whole body receptive field of dorsal horn multireceptive neurones.</a> Brain Res Brain Res Rev. 40 (1-3), 29-44 (2002).</li><li>Yarnitsky, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+on+practice+of+conditioned+pain+modulation+(CPM)+testing.">Recommendations on practice of conditioned pain modulation (CPM) testing.</a> Eur J Pain. 19 (6), 805-806 (2015).</li><li>Rolke, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+sensory+testing:+a+comprehensive+protocol+for+clinical+trials.">Quantitative sensory testing: a comprehensive protocol for clinical trials.</a> Eur J Pain. 10 (1), 77-88 (2006).</li><li>Wilder-Smith, O. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> A Paradigm-Shift in Pain Medicine: Implementing a Systematic Approach to Altered Pain Processing in Everyday Clinical Practice. Based on Quantitative Sensory Testing. , (2013).</li><li>Nasri-Heir, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+pain+modulation+in+patients+with+persistent+postendodontic+pain.">Altered pain modulation in patients with persistent postendodontic pain.</a> Pain. 156 (10), 2032-2041 (2015).</li><li>Treede, R. D., Meyer, R. A., Raja, S. N., Campbell, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peripheral+and+central+mechanisms+of+cutaneous+hyperalgesia.">Peripheral and central mechanisms of cutaneous hyperalgesia.</a> Prog Neurobiol. 38 (4), 397-421 (1992).</li></ol>

作者没有利益冲突或任何财务利益的披露。

我们的方法, 量化压力疼痛阈值, 电子疼痛阈值, 和 CPM 可以成功地应用在临床的情况下, 因为它的短时间 (约20分钟)。我们先前已经表明, 术后早期获得的压力疼痛值可能对预测乳腺癌手术中长期随访的持续疼痛有价值8。在我们的研究中, 虽然电子疼痛阈值 CPM 并不能预测持续性疼痛, 但其他的则表明这些措施对于其他程序513可能有价值。使用电痛阈值的一个限制是它可能代表一种非自然刺激。然而, 它绕过了局部调制, 并且它提供了非常精确的强度和定时控制, 提高了重复性, 导致我们将它包含在当前的协议14中。替代性刺激模式, 如热, 可能被用来取代本议定书的电刺激。
我们希望详述一个限定的, 但有价值的, 定量的感官测试范式将导致更广泛的应用这些措施的背景下, 持续疼痛的研究乳腺癌。一旦更多的围手术期定量感觉测试数据成为可用, 它可能是可能的, 以确定亚群的病人, 有发展持续后疼痛的高风险, 并定制围治疗, 以尽量减少风险最终形成持续的疼痛。

慢性疼痛后手术, 持续后疼痛, 是一个重要的条件, 导致严重的症状负担和较低的生活质量1。持续的手术后疼痛仍未得到很好的理解, 但被广泛认为是手术后3月以上的疼痛2。这种情况是常见的, 其患病率的估计范围从10% 到50% 的所有后患者3。高危程序包括乳房手术4、开胸术的5、截肢6和疝气修复7。持续的后疼痛是相对难治的治疗, 从而引起了潜在的预防策略和治疗的兴趣。更好地了解预测和描述持续的术后疼痛, 将有助于确定可能需要额外治疗的患者的子集, 以优化其围手术期疼痛管理。
最近的研究表明, 在外科手术中, 疼痛阈值的异常变化可能对乳腺癌手术的长期持续疼痛的发展有预测价值8。其他人强调了条件性疼痛调制 (CPM) 效应在预测持续性术后疼痛方面的重要性, 例如, 在开胸手术后的持续疼痛5。CPM 是弥漫性有害抑制控制的行为关联, 一种生理现象, 来自外周 c 纤维的输入导致来自异位场的 c 纤维介导的所有传入刺激的脑干的弥漫性抑制9.CPM 效应是通过将阈值与有害刺激进行比较来衡量的, 这是在第二种不同刺激的应用前后测量的, 这被称为条件反射刺激10。
目前标准化的定量感官测试 (QST) 协议, 如德国研究网络神经病理性疼痛协议11是相当广泛, 可能不适合在外科病人的执行。本出版物的目的是详述一个简短和标准化的协议, 以获得疼痛阈值和 CPM 效果测量乳腺癌手术患者。本协议来自于我们大学与丹麦奥尔堡大学的合作协议12。

<table>
	<tbody>
		<tr>
			<td>Bed</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of hospital bed or medical exam table</td>
		</tr>
		<tr>
			<td>Desk</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available desk</td>
		</tr>
		<tr>
			<td>Office chair</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available office chair</td>
		</tr>
		<tr>
			<td>Force FPX 50 Pressure algometer</td>
			<td>Wagner Instruments, Greenwich, CT, USA</td>
			<td>N/A</td>
			<td>Pressure algometer with a 1.0 cm2 circular tip to deliver pressure to perform pressure pain threshold measurements</td>
		</tr>
		<tr>
			<td>Desktop computer</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available Windows computer to run QST-IV Stimulus Manager software on to control the QST-IV stimulator</td>
		</tr>
		<tr>
			<td>QST-IV Stimulus Manager</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>Software to control the settings of QST-IV electrical stimulator</td>
		</tr>
		<tr>
			<td>QST-IV Electrical Stimulator</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>Electrical quantitative sensory testing device with a patient operated switch. Device used to deliver electrical current to perform the electrical threshold measurements</td>
		</tr>
		<tr>
			<td>VAS Slider</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>The VAS slider consists of a box with a mobile lever on a horizontal bar that represents the VAS and is connected to the QST-IV.</td>
		</tr>
		<tr>
			<td>Kendall H34SG 50 x 45 mm</td>
			<td>Covidien, Mansfield, USA</td>
			<td>N/A</td>
			<td>Self-adhesive skin electrodes to apply to the measurement points on the skin to deliver electrical stimualtion</td>
		</tr>
		<tr>
			<td>Crushed Ice</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Ice generated by ice machine to cool water sufficiently for the cold pressor test</td>
		</tr>
		<tr>
			<td>Bucket</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available 10 L bucket</td>
		</tr>
		<tr>
			<td>Surgical skin marker</td>
			<td>Covidien, Mansfield, USA</td>
			<td>N/A</td>
			<td>Any type of commercially available surgical skin marker</td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available stopwatch</td>
		</tr>
		<tr>
			<td>Measurement form</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Score form provided in the manuscript</td>
		</tr>
		<tr>
			<td>Pencil</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available pencil</td>
		</tr>
		<tr>
			<td>Thermometer</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Thermometer to measure water temperature of ice water</td>
		</tr>
		<tr>
			<td>Ruler</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available ruler</td>
		</tr>
	</tbody>
</table>

a quantitative sensory testing paradigm to obtain measures of pain processing in patients undergoing breast cancer surgery

慢性疼痛后手术, 持续后疼痛, 是一个重要的高度普遍的情况下, 造成重大症状负担和降低生活质量。持续的后疼痛是相对顽固的治疗, 因此产生了很高的需要预防策略和治疗。因此, 确定患持续性疼痛的风险患者是一个积极进行的研究领域。最近有人证实, 中心疼痛处理的围手术期中断可能能够预测乳腺癌患者长期随访的持续后疼痛。本报告的目的是提出一个简短的协议, 以获得不同的刺激在多个地点的疼痛阈值, 并在乳腺癌患者的内源性镇痛措施。我们在临床上成功地运用了这一方法, 并从临床研究中得到了一些有代表性的结果。

在以前发表的临床试验中, 妇女 (N = 94) 接受乳腺癌手术, 我们使用本报告中描述的协议8测量了电和压痛阈值以及 CPM。我们在手术后的一年中, 在不同的时间点执行了测试范例。我们发现女性在乳腺癌手术后12月内持续后疼痛, 定义为 > 30 毫米的 VAS, 在手术后早期和晚期都表现出较低的压力痛阈值。图 3详细介绍了在手术后早期 (图 3A) 和晚期 (图 3B) 的压力痛阈值的变化。为了简单起见, 在不同测量部位的压力痛阈值是发货的, 并表示为变化与基线。使用逻辑回归, 我们发现, 在手术后5天的每10% 低阈值, 患者50% 更有可能出现慢性疼痛12月后手术 (置信区间10–100% 更可能, p = 0.01)。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56918/56918fig1v2.jpg"> 图 1:软件界面的屏幕截图和用于电气 QST 测量的适当设置.<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56918/56918fig1v2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56918/56918fig2v2.jpg"> 图 2:评分表.N: 牛顿;mA: 毫安;增值: 视觉模拟秤;EDT: 电检测门限;EPT: 电痛阈;CPM, 有条件的疼痛调制;PA: 压力 algometry;白板: 冰水桶试验。<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56918/56918fig2v2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56918/56918fig3.jpg"> 图 3: 在乳腺癌手术后一年内的压力疼痛阈值的变化.面板A和B分别显示了术后早期和晚期时间点的平均± SE。时间点被标记为与手术相关, 基线评估在手术前1周。分析采用因子 "时间" 和 "持续性疼痛" 的混合模型分析, Bonferroni 修正了临时对各个时间点的比较。* 术后12月无持续性疼痛患者 (α级 0.05), 具体: p = 0.02 天 5;p < 0.01 在15天;p < 0.01 在30天;p = 0.02 在3月;p ≤0.01 为6月, 并且;p = 0.03 在12月。此图已从 van 德et al中进行了修改。8.<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56918/56918fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

Watch this Scientific Journal Video about A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery at JoVE.com

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

持续的后疼痛可能与疼痛处理的变化有关。通过评估对标准化刺激的反应疼痛, 可以阐明疼痛处理的变化。我们提出的方法, 以获得不同刺激的疼痛阈值和一项措施内源性镇痛的病人进行乳腺癌手术。

一种定量感官检测方法在乳腺癌手术患者疼痛处理中的研究

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

a-quantitative-sensory-testing-paradigm-to-obtain-measures-pain

Nanyang Technological University

Research

JoVE Journal

Medicine

9.2K 次观看.  Radboud University Medical Center. 持续的后疼痛可能与疼痛处理的变化有关。通过评估对标准化刺激的反应疼痛, 可以阐明疼痛处理的变化。我们提出的方法, 以获得不同刺激的疼痛阈值和一项措施内源性镇痛的病人进行乳腺癌手术。

视频: A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

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

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

在接受深部脑刺激手术术中唤醒人类行为任务

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

Quantitative Autonomic Testing

Disorders associated with dysfunction of autonomic nervous system are quite common yet frequently unrecognized. Quantitative autonomic testing can be invaluable tool for evaluation of these disorders, both in clinic and research. There are number of autonomic tests, however, only few were validated clinically or are quantitative. Here, fully quantitative and clinically validated protocol for testing of autonomic functions is presented. As a bare minimum the clinical autonomic laboratory should have a tilt table, ECG monitor, continuous noninvasive blood pressure monitor, respiratory monitor and a mean for evaluation of sudomotor domain. The software for recording and evaluation of autonomic tests is critical for correct evaluation of data. The presented protocol evaluates 3 major autonomic domains: cardiovagal, adrenergic and sudomotor. The tests include deep breathing, Valsalva maneuver, head-up tilt, and quantitative sudomotor axon test (QSART). The severity and distribution of dysautonomia is quantitated using Composite Autonomic Severity Scores (CASS). Detailed protocol is provided highlighting essential aspects of testing with emphasis on proper data acquisition, obtaining the relevant parameters and unbiased evaluation of autonomic signals. The normative data and CASS algorithm for interpretation of results are provided as well.

Standardized, comprehensive and fully quantitative testing of autonomic functions is described. The autonomic tests consist of evaluation of all three major autonomic domains including cardiovagal, adrenergic and sudomotor. The severity and distribution of dysautonomia is quantitated using Composite Autonomic Severity Scores.

定量自主测试

Disorders associated with dysfunction of autonomic nervous system are quite common yet frequently unrecognized. Quantitative autonomic testing can be ...

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

危重病人中的应用手册肌力测试:下肢肌力测量方法

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

A comprehensive overview of the techniques involved in generating a mouse model of oral cancer and quantitative monitoring of tumor invasion within the tongue through multi-photon microscopy of labeled cells is presented. This system can serve as a useful platform for the molecular assessment and drug efficacy of anti-invasive compounds.

多光子成像在口腔鳞状细胞癌原位小鼠模型的肿瘤细胞的侵袭

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these techniques, patients hold their breath while radiotherapy is delivered, pushing the heart down and away from the radiotherapy field. Despite clear dosimetric benefits, these techniques are not yet in widespread use. One reason for this is that commercially available solutions require specialist equipment, necessitating not only significant capital investment, but often also incurring ongoing costs such as a need for daily disposable mouthpieces. The voluntary breath-hold technique described here does not require any additional specialist equipment. All breath-holding techniques require a surrogate to monitor breath-hold consistency and whether breath-hold is maintained. Voluntary breath-hold uses the distance moved by the anterior and lateral reference marks (tattoos) away from the treatment room lasers in breath-hold to monitor consistency at CT-planning and treatment setup. Light fields are then used to monitor breath-hold consistency prior to and during radiotherapy delivery.

The current priority in breast cancer radiotherapy is to reduce cardiac doses without compromising target tissue coverage. The voluntary breath-hold technique described here is a simple, inexpensive solution to this problem and capable of being instituted widely without the need for specialized equipment.

自愿屏气技术减少心脏剂量的左乳房放射治疗

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these ...

Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery (BCS). Optical imaging, in particular near-infrared fluorescence (NIRF) imaging, might reduce the frequency of positive surgical margins following BCS by providing the surgeon with a tool for pre- and intraoperative tumor localization in real-time. In the current study, the potential of NIRF-guided BCS is evaluated using tissue-simulating breast phantoms for reasons of standardization and training purposes.
Breast phantoms with optical characteristics comparable to those of normal breast tissue were used to simulate breast conserving surgery. Tumor-simulating inclusions containing the fluorescent dye indocyanine green (ICG) were incorporated in the phantoms at predefined locations and imaged for pre- and intraoperative tumor localization, real-time NIRF-guided tumor resection, NIRF-guided evaluation on the extent of surgery, and postoperative assessment of surgical margins. A customized NIRF camera was used as a clinical prototype for imaging purposes.
Breast phantoms containing tumor-simulating inclusions offer a simple, inexpensive, and versatile tool to simulate and evaluate intraoperative tumor imaging. The gelatinous phantoms have elastic properties similar to human tissue and can be cut using conventional surgical instruments. Moreover, the phantoms contain hemoglobin and intralipid for mimicking absorption and scattering of photons, respectively, creating uniform optical properties similar to human breast tissue. The main drawback of NIRF imaging is the limited penetration depth of photons when propagating through tissue, which hinders (noninvasive) imaging of deep-seated tumors with epi-illumination strategies.

Near-infrared fluorescence (NIRF) imaging may improve therapeutic outcome of breast cancer surgery by enabling intraoperative tumor localization and evaluation of surgical margin status. Using tissue-simulating breast phantoms containing fluorescent tumor-simulating inclusions, potential clinical applications of NIRF imaging in breast cancer patients can be assessed for standardization and training purposes.

组织鬼怪模拟，以评估乳癌手术潜在的近红外荧光成像中的应用

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery ...

In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose

High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the contribution of omental adipose tissue to ovarian cancer progression remains understudied. Omental adipose is unusual in that it contains structures known as milky spots, which are comprised of B, T, and NK cells, macrophages, and progenitor cells surrounding dense nests of vasculature. Milky spots play a key role in the physiologic functions of the omentum, which are required for peritoneal homeostasis. We have shown that milky spots also promote ovarian cancer metastatic colonization of peritoneal adipose, a key step in the development of peritoneal metastases. Here we describe the approaches we developed to evaluate and quantify milky spots in peritoneal adipose and study their functional contribution to ovarian cancer cell metastatic colonization of omental tissues both in vivo and ex vivo. These approaches are generalizable to additional mouse models and cell lines, thus enabling the study of ovarian cancer metastasis formation from initial localization of cells to milky spot structures to the development of widespread peritoneal metastases.

In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose

We outline a protocol that implements both in vivo and ex vivo approaches to study ovarian cancer colonization of peritoneal adipose tissues, particularly the omentum. Furthermore, we present a protocol to quantitate and analyze immune cell-structures in the omentum known as milky spots, which promote metastases of peritoneal adipose.

在体内和体外途径研究银河系结构现货卵巢癌转移定植腹膜脂肪

High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of ...

Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis

This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer metastasis. The 4T1 cells expressing GFP in combination with imaging and confocal microscopy are used to monitor tumor growth, track metastasizing tumor cells, and quantify the metastatic burden. These approaches are supplemented by digital histopathology that allows the automated and unbiased quantification of metastases. In this method the routinely prepared histological lung sections, which are stained with hematoxylin and eosin, are scanned and converted to the digital slides that are then analyzed by the self-trained pattern recognition software. In addition, we describe the flow cytometry approaches with the use of multiple cell surface markers to identify alveolar macrophages in the lungs. To determine impact of alveolar macrophages on metastases and antitumor immunity these cells are depleted with the clodronate-containing liposomes administrated intranasally to tumor-bearing mice. This approach leads to the specific and efficient depletion of this cell population as confirmed by flow cytometry. Tumor volumes and lung metastases are evaluated in mice depleted of alveolar macrophages, to determine the role of these cells in the metastatic progression of breast cancer.

Here we describe the model and approach to study functions of pulmonary alveolar macrophages in cancer metastasis. To demonstrate the role of these cells in metastasis, the syngeneic (4T1) model of breast cancer in conjunction with the depletion of alveolar macrophage with clodronate liposomes was used.

研究肺泡巨噬细胞的作用乳腺癌转移

This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer ...

A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as many as 50% of elderly patients suffer from neurologic complications like delirium. Also, the capacity to heal and regenerate tissue after surgery decreases with age, and can impact the quality of fracture repair and even osseous integration of implants. Thus, a better understanding of mechanisms that drive these age-dependent changes could provide strategic targets to minimize risk for such complications and optimize outcomes. Here, we introduce a clinically relevant mouse model of tibial fracture. The postoperative changes in these mice mimic some of the cognitive impairments commonly observed after routine orthopedic surgery in humans. Briefly, an incision is performed in the right hind limb under strictly aseptic conditions. Muscles are disassociated, and a 0.38-mm stainless steel pin is inserted into the upper crest of the tibia, inside the intramedullary canal. Osteotomy is then performed, and the wound is stapled. We have used this model to investigate the effects of surgical trauma on postoperative neuroinflammation and behavioral changes. By applying this fracture model in combination with parabiosis, a surgical model in which 2 mice are anastomosed, we have studied cells and secreted factors that systemically rejuvenate organ function and tissue regeneration after injury. By following our step-by-step protocol, these models can be reproduced with high fidelity, and can be adapted to interrogate many biologic pathways that are altered by surgical trauma.

This protocol describes a mouse model of orthopedic surgery that has been used to study mechanisms of postoperative neuroinflammation and behavioral changes, and when combined with parabiosis, to study tissue regeneration during aging.

骨科手术的小鼠模型研究术后认知功能障碍与组织再生

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and ...