作者承认以下资金来源:杜肯大学教师发展基金的拨款颁发给金佰利Szucs博士和Alex Kranjec博士和本笃Kolber博士和马修Kostek，博士学位。我们也承认雷切尔Sweetnich从授予Sweetnich（导师:Szucs和Kostek）杜肯大学本科疼痛体验的研究实验计划援助和资金。

以人类为对象所有测试应该由机构审查委员会在个别机构的批准。对于目前的研究中描述的所有测试人体试验是经杜肯大学机构审查委员会。培训和各措施说明如下: 1.皮肤机械敏感性测定13 注:已登记的参与者被要求在椅子上坐下，与为下肢支持进行测试。该法包括确定无害皮肤刺激灵敏度阈值。刺激设置有标准的感官评估的von Frey长丝（见设备部分）。这些小尼龙长丝每个应用单一力（从0.078万（0.008英寸七）4.08万（1.0克））。 <ol><li>第一个实验试验开始之前，请允许参与者感受和操控细丝。给网络感叹的参与者，让他们轻轻地弯曲，对他们的手皮肤。 </li><li>在每一次试验，让拍摄对象从看他们的前臂或小腿了。适用灯丝主体的前臂或小腿，直到鞠躬，并询问他们是否觉得灯丝。 </li><li>用最小的灯丝启动（0.078 MN;低于人体检测的感觉阈限），开展关于这个问题的前臂或小腿每个灯丝五位审判。 <ol><li>与各灯丝（ 例如，0.078 MN长丝），应用灯丝四次的"正"的试验。 </li><li>对于其他审判，不适用灯丝，但还是问这个问题，如果他们觉得灯丝。 注:此"负"试将随机插入四个"积极"试验和旨在测试为假的反应（ 即主题认为，他们觉得即使没有刺激应用的东西）。这是必要的感觉阈TESTIN克，因为在感觉系统和/或其它刺激（ 如，有微风）随机噪声会导致错误的响应。 </li></ol></li><li>如果主体检测阳性试验和灯丝0负试验≥3，然后录制长丝作为数据表单上的主题的"机械感觉阈限"。 </li><li>对于单丝，如果对象检测&lt;真实试验的2和/或&gt;假试验0，然后开始另一轮的5次试验与下次最大长丝直到达到感觉阈值。 注:感官阈值变化为人类受试者，但在经验，他们通常是从1.57-9.81 MN范围（数据未显示）。这力量足以感受到光无害的压力。典型的检测时间为每个身体部位（前臂和小腿）为约5分钟。另外，也可以测量针状疼痛与这些长丝，但是这通常需要使用大直径的长丝。 </li></ol> 2。辐射热敏感性测定35 注:已登记的参与者被要求在椅子上坐下，与为下肢支持进行测试。该测定涉及确定用于非疼痛热变化和痛苦热刺激的敏感性阈值。刺激设置有热辐射装置35。这个装置使用一个聚焦光束穿过一块0.64毫米厚的安全玻璃缓慢加热的受试者的皮肤（见下文中的仪器部分）。 <ol><li>培训和实验性试验开始前，显示设备的主题;让他们感到自己的手的刺激。 </li><li>向受试者休息其前臂或小腿上的室温玻璃板，它应覆盖有除了用于刺激呈现小窗口的橡胶绝缘片。 注:绝缘片使主题集中于刺激呈现在无冷却SEnsation与将一个人的身体对抗的室温对象相关联。 </li><li>使用镜，定位下对受验者的前臂或小腿（ 图1）的显着区域中的光源。 注:当腿或臂从玻璃的表面凸出，所述热刺激自动停止，因为在试验的开始，然后被记录为时间"延迟响应"。 </li><li>完成两个试验中两个不同的显着的区域上每个肢体各试验（无害温度检测和疼痛阈值），以避免在单一地点重新测试。 </li><li>对于无伤大雅的温度检测试验，问这个问题时，他们感到温度的变化，以提高他们的腿或手臂，或按下"停止"按钮。 <ol><li>因此，典型的缩回阈值出现在约10秒到试，从而使设备20秒后关闭设置设备。要做到这一点痛阈值，设置德维CE坡道，使得刺激在10秒达到47℃的温度。 注:对于无害的温度检测试验中，在玻璃上在阈值的典型的温度是37℃（99°F）。在痛阈试验中，受试者被告知，当他们感到"温暖无害或热"的刺激过渡，以提高他们的腿或手臂，或按下"停止"按钮，"痛苦的热量。"在阈玻璃上的典型的温度是〜47℃（121°F）。在20秒的截止时间点试验的最高温度为50℃，其远低于会导致在人中36的组织损伤的累积温度。 </li></ol></li><li>使用恒温法28（加热块），以评估的质量和热痛的不愉快。使用加热块，用于刺激的温度设定为45℃。 注:45°C是是典型的最小stimu标准温度必要杆菌感到热痛和已知激活TRPV1伤害感受器29。 <ol><li>步骤2.7.2之前，说明标准0-10 VAS并显示在10cm线向受试者。通知对"质量规模"，"0"表示"不痛"和"10"表示"最严重的疼痛可以想象的主题"，并表示对"不愉快的规模"，"0"表示"不愉快"和" 10"表示"最不愉快的感觉想象"（ 如图2）。 </li><li>为3秒施加刺激3厘米（×5厘米加热块），以标记的位置上的左前臂或小腿（ 如图1在现场标记为"T"）。 </li><li>紧接着的刺激，让拍摄对象，以评估使用标准的0-10 VAS疼痛的质量和不愉快。 </li></ol></li></ol> 3.压力敏感性测定13,37 注:已登记的参与者被要求在椅子上坐下，与为下肢支持进行测试。该测定涉及确定用于痛苦压力刺激的灵敏度阈值，然后确定在一个单独的试验，同样的压力的质量和不愉快。刺激设置有标准的临床压力痛觉计（见下文中的材料和设备表仪器部分）。此装置由连接到压力米2厘米探针。 <ol><li>第一次训练和实验审判之前，让受刺激应用到自己的认真监督。 </li><li>对于痛阈审判，放在主体的前臂或小腿探头，逐步施加压力。 <ol><li>每个完整两个试验的前臂和小腿在两个不同的位点（每个肢），以避免一个区域中的破坏。 </li><li>在审判过程中，施加压力逐渐，直到"无害压"到"痛苦的压力"刺激过渡。让拍摄对象说"停"在这一点上，并从主体的前臂或小腿的刺激。 </li><li>取下主题的痛觉计。该装置自动记录施加最大的压力。记录此为"压力痛阈值"为审判。 </li></ol></li><li>通知课题，定压试验是下一个。 <ol><li>确定所述受试者中的压力阈值之后，应用在相对肢的附加试验，以确定与痛苦压力刺激（在第三测试点）相关联的被检者的痛苦。匹配精确地刺激了基准试验期间确定（ 例如，如果前臂基线试验表明的50 N的压力阈值，则该主题将被要求来评估刺激的疼痛）主体的痛阈值。 </li><li>在这项试验中，要求日Ë主题，以评估在3秒内给予压力刺激的质量和不愉快。 </li><li>使用标准的0-10增值服务。通知对"质量规模"，"0"表示"不痛"和"10主题为"代表"最严重的疼痛可想而知。"在"规模不愉快"，"0"表示"不愉快"和"10"表示"最不愉快的感觉可想而知。" </li><li>这次审判中，适用于疼痛刺激，然后问这个问题来评估疼痛（对上述两种增值业务）。 </li></ol></li></ol> 4.可靠性研究注:要检查协议的可靠性，我们进行了一个小的研究，受试者的收视率一雄一雌考官之间进行比较。 <ol><li>通过张贴传单征集参与者。有谁符合纳入标准有兴趣的志愿者（参考1）参与一个或其中研究描述和测试技术被证明ientation会话。 </li><li>问潜在的志愿者的问题，并让他们阅读并签署由大学IRB批准的知情同意文件。 注:这两个考官这项研究是谁被研究者谁拥有从疼痛测量和管理的临床和实验室及神经感觉经验培训的实验室技术人员（一公一母）。 </li><li>测试所有受试者具有两个不同审查员，与两个检查相隔30分钟。 </li><li>到本研究评估评判间的可靠性，计算组内相关系数（型号3,2）[ICC（3,2）]用方差分析（ANOVA）对每个因变量绝对协议的双向混合分析（总共八个）38。统计软件可用于所有的统计分析。 </li></ol>

<ol><li>Analysts, G. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Pain+Management+-+A+Global+Strategic+Business+Report%5BTitle%5D)+AND+%22Global+Industry+Analysts%22%5BJournal%5D)">Pain Management - A Global Strategic Business Report.</a> Global Industry Analysts. , 727(2012).</li>
<li><a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=%22AAPM+Facts+and+Figures+on+Pain%22">AAPM Facts and Figures on Pain</a>. Medicine, A. .A. .o.P. , (2015).</li>
<li>Loeser, J. D., Treede, R. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+Kyoto+protocol+of+IASP+Basic+Pain+Terminology%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">The Kyoto protocol of IASP Basic Pain Terminology.</a> Pain. 137 (3), 473-477 (2008).</li>
<li>Clauw, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Fibromyalgia%3A+a+clinical+review%5BTitle%5D)+AND+%22JAMA%22%5BJournal%5D)">Fibromyalgia: a clinical review.</a> JAMA. 311 (15), 1547-1555 (2014).</li>
<li>Haanpaa, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((NeuPSIG+guidelines+on+neuropathic+pain+assessment%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">NeuPSIG guidelines on neuropathic pain assessment.</a> Pain. 152 (1), 14-27 (2011).</li>
<li>Cruccu, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Recommendations+for+the+clinical+use+of+somatosensory-evoked+potentials%5BTitle%5D)+AND+%22Clin+Neurophysiol%22%5BJournal%5D)">Recommendations for the clinical use of somatosensory-evoked potentials.</a> Clin Neurophysiol. 119 (8), 1705-1719 (2008).</li>
<li>Backonja, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Value+of+quantitative+sensory+testing+in+neurological+and+pain+disorders%3A+NeuPSIG+consensus%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus.</a> Pain. 154 (9), 1807-1819 (2013).</li>
<li>Mainka, T., Maier, C., Enax-Krumova, E. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Neuropathic+pain+assessment%3A+update+on+laboratory+diagnostic+tools%5BTitle%5D)+AND+%22Curr+Opin+Anaesthesiol%22%5BJournal%5D)">Neuropathic pain assessment: update on laboratory diagnostic tools.</a> Curr Opin Anaesthesiol. 28 (5), 537-545 (2015).</li>
<li>Maier, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Quantitative+sensory+testing+in+the+German+Research+Network+on+Neuropathic+Pain+%28DFNS%29%3A+somatosensory+abnormalities+in+1236+patients+with+different+neuropathic+pain+syndromes%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.</a> Pain. 150 (3), 439-450 (2010).</li>
<li>Magerl, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reference+data+for+quantitative+sensory+testing+%28QST%29%3A+refined+stratification+for+age+and+a+novel+method+for+statistical+comparison+of+group+data%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data.</a> Pain. 151 (3), 598-605 (2010).</li>
<li>Pfau, D. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Quantitative+sensory+testing+in+the+German+Research+Network+on+Neuropathic+Pain+%28DFNS%29%3A+reference+data+for+the+trunk+and+application+in+patients+with+chronic+postherpetic+neuralgia%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.</a> Pain. 155 (5), 1002-1015 (2014).</li>
<li>Olesen, A. E., Andresen, T., Staahl, C., Drewes, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Human+experimental+pain+models+for+assessing+the+therapeutic+efficacy+of+analgesic+drugs%5BTitle%5D)+AND+%22Pharmacol+Rev%22%5BJournal%5D)">Human experimental pain models for assessing the therapeutic efficacy of analgesic drugs.</a> Pharmacol Rev. 64 (3), 722-779 (2012).</li>
<li>Rolke, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Quantitative+sensory+testing%3A+a+comprehensive+protocol+for+clinical+trials%5BTitle%5D)+AND+%22Eur+J+Pain%22%5BJournal%5D)">Quantitative sensory testing: a comprehensive protocol for clinical trials.</a> Eur J Pain. 10 (1), 77-88 (2006).</li>
<li>Angst, M. S., Tingle, M., Phillips, N. G., Carvalho, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Determining+heat+and+mechanical+pain+threshold+in+inflamed+skin+of+human+subjects%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">Determining heat and mechanical pain threshold in inflamed skin of human subjects.</a> J Vis Exp. (23), e1092(2009).</li>
<li>Dyck, P. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cool%2C+warm%2C+and+heat-pain+detection+thresholds%3A+testing+methods+and+inferences+about+anatomic+distribution+of+receptors%5BTitle%5D)+AND+%22Neurology%22%5BJournal%5D)">Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors.</a> Neurology. 43 (8), 1500-1508 (1993).</li>
<li>Tena, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reproducibility+of+Electronic+Von+Frey+and+Von+Frey+monofilaments+testing%5BTitle%5D)+AND+%22Clin+J+Pain%22%5BJournal%5D)">Reproducibility of Electronic Von Frey and Von Frey monofilaments testing.</a> Clin J Pain. 28 (4), 318-323 (2012).</li>
<li>Staahl, C., Christrup, L. L., Andersen, S. D., Arendt-Nielsen, L., Drewes, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+comparative+study+of+oxycodone+and+morphine+in+a+multi-modal%2C+tissue-differentiated+experimental+pain+model%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">A comparative study of oxycodone and morphine in a multi-modal, tissue-differentiated experimental pain model.</a> Pain. 123 (1-2), 28-36 (2006).</li>
<li>Reddy, K. S., Naidu, M. U., Rani, P. U., Rao, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Human+experimental+pain+models%3A+A+review+of+standardized+methods+in+drug+development%5BTitle%5D)+AND+%22J+Res+Med+Sci%22%5BJournal%5D)">Human experimental pain models: A review of standardized methods in drug development.</a> J Res Med Sci. 17 (6), 587-595 (2012).</li>
<li>Adriaensen, H., Gybels, J., Handwerker, H. O., Van Hees, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Nociceptor+discharges+and+sensations+due+to+prolonged+noxious+mechanical+stimulation--a+paradox%5BTitle%5D)+AND+%22Hum+Neurobiol%22%5BJournal%5D)">Nociceptor discharges and sensations due to prolonged noxious mechanical stimulation--a paradox.</a> Hum Neurobiol. 3 (1), 53-58 (1984).</li>
<li>Burke, D., Mackenzie, R. A., Skuse, N. F., Lethlean, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cutaneous+afferent+activity+in+median+and+radial+nerve+fascicles%3A+a+microelectrode+study%5BTitle%5D)+AND+%22J+Neurol+Neurosurg+Psychiatry%22%5BJournal%5D)">Cutaneous afferent activity in median and radial nerve fascicles: a microelectrode study.</a> J Neurol Neurosurg Psychiatry. 38 (9), 855-864 (1975).</li>
<li>Woolf, C. J., Max, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Mechanism-based+pain+diagnosis%3A+issues+for+analgesic+drug+development%5BTitle%5D)+AND+%22Anesthesiology%22%5BJournal%5D)">Mechanism-based pain diagnosis: issues for analgesic drug development.</a> Anesthesiology. 95 (1), 241-249 (2001).</li>
<li>Wylde, V., Palmer, S., Learmonth, I. D., Dieppe, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Test-retest+reliability+of+Quantitative+Sensory+Testing+in+knee+osteoarthritis+and+healthy+participants%5BTitle%5D)+AND+%22Osteoarthritis+Cartilage%22%5BJournal%5D)">Test-retest reliability of Quantitative Sensory Testing in knee osteoarthritis and healthy participants.</a> Osteoarthritis Cartilage. 19 (6), 655-658 (2011).</li>
<li>Geber, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Test-retest+and+interobserver+reliability+of+quantitative+sensory+testing+according+to+the+protocol+of+the+German+Research+Network+on+Neuropathic+Pain+%28DFNS%29%3A+a+multi-centre+study%5BTitle%5D)+AND+%22Pain%22%5BJournal%5D)">Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS): a multi-centre study.</a> Pain. 152 (3), 548-556 (2011).</li>
<li>Green, B. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Temperature+perception+on+the+hand+during+static+versus+dynamic+contact+with+a+surface%5BTitle%5D)+AND+%22Atten+Percept+Psychophys%22%5BJournal%5D)">Temperature perception on the hand during static versus dynamic contact with a surface.</a> Atten Percept Psychophys. 71 (5), 1185-1196 (2009).</li>
<li>Green, B. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Referred+thermal+sensations%3A+warmth+versus+cold%5BTitle%5D)+AND+%22Sens+Processes%22%5BJournal%5D)">Referred thermal sensations: warmth versus cold.</a> Sens Processes. 2 (3), 220-230 (1978).</li>
<li>Green, B. G., Lederman, S. J., Stevens, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+effect+of+skin+temperature+on+the+perception+of+roughness%5BTitle%5D)+AND+%22Sens+Processes%22%5BJournal%5D)">The effect of skin temperature on the perception of roughness.</a> Sens Processes. 3 (4), 327-333 (1979).</li>
<li>Stevens, J. C., Green, B. G., Krimsley, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Punctate+pressure+sensitivity%3A+effects+of+skin+temperature%5BTitle%5D)+AND+%22Sens+Processes%22%5BJournal%5D)">Punctate pressure sensitivity: effects of skin temperature.</a> Sens Processes. 1 (3), 238-243 (1977).</li>
<li>Fowler, C. J., Sitzoglou, K., Ali, Z., Halonen, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+conduction+velocities+of+peripheral+nerve+fibres+conveying+sensations+of+warming+and+cooling%5BTitle%5D)+AND+%22J+Neurol+Neurosurg+Psychiatry%22%5BJournal%5D)">The conduction velocities of peripheral nerve fibres conveying sensations of warming and cooling.</a> J Neurol Neurosurg Psychiatry. 51 (9), 1164-1170 (1988).</li>
<li>Tominaga, M. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aTominaga%2C+M+%22Frontiers+in+Neuroscience%22">Frontiers in Neuroscience</a>. Liedtke, W. B., Heller, S. , CRC Press/Taylor & Francis. Boca Raton. (2007).</li>
<li>Yarnitsky, D., Ochoa, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Warm+and+cold+specific+somatosensory+systems.+Psychophysical+thresholds%2C+reaction+times+and+peripheral+conduction+velocities%5BTitle%5D)+AND+%22Brain%22%5BJournal%5D)">Warm and cold specific somatosensory systems. Psychophysical thresholds, reaction times and peripheral conduction velocities.</a> Brain. 114 (Pt 4), 1819-1826 (1991).</li>
<li>Hughes, A. M., Rhodes, J., Fisher, G., Sellers, M., Growcott, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Assessment+of+the+effect+of+dextromethorphan+and+ketamine+on+the+acute+nociceptive+threshold+and+wind-up+of+the+second+pain+response+in+healthy+male+volunteers%29%5BTitle%5D)+AND+%22Br+J+Clin+Pharmacol%22%5BJournal%5D)">Assessment of the effect of dextromethorphan and ketamine on the acute nociceptive threshold and wind-up of the second pain response in healthy male volunteers).</a> Br J Clin Pharmacol. 53 (6), 604-612 (2002).</li>
<li>Handwerker, H. O., Kobal, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Psychophysiology+of+experimentally+induced+pain%5BTitle%5D)+AND+%22Physiol+Rev%22%5BJournal%5D)">Psychophysiology of experimentally induced pain.</a> Physiol Rev. 73 (3), 639-671 (1993).</li>
<li>Taylor, D. J., McGillis, S. L., Greenspan, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Body+site+variation+of+heat+pain+sensitivity%5BTitle%5D)+AND+%22Somatosens+Mot+Res%22%5BJournal%5D)">Body site variation of heat pain sensitivity.</a> Somatosens Mot Res. 10 (4), 455-465 (1993).</li>
<li>Drury, D. G., Stuempfle, K. J., Shannon, R., Miller, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+investigation+of+exercise-induced+hypoalgesia+after+isometric+and+cardiovascular+exercise%5BTitle%5D)+AND+%22Journal+of+Exerc+Physiol%22%5BJournal%5D)">An investigation of exercise-induced hypoalgesia after isometric and cardiovascular exercise.</a> Journal of Exerc Physiol. 7 (4), (2004).</li>
<li>Sternberg, W. F., Bokat, C., Kass, L., Alboyadjian, A., Gracely, R. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Sex-dependent+components+of+the+analgesia+produced+by+athletic+competition%5BTitle%5D)+AND+%22J+Pain%22%5BJournal%5D)">Sex-dependent components of the analgesia produced by athletic competition.</a> J Pain. 2 (1), 65-74 (2001).</li>
<li>Yarmolenko, P. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Thresholds+for+thermal+damage+to+normal+tissues%3A+an+update%5BTitle%5D)+AND+%22Int+J+Hyperthermia%22%5BJournal%5D)">Thresholds for thermal damage to normal tissues: an update.</a> Int J Hyperthermia. 27 (4), 320-343 (2011).</li>
<li>Kinser, A. M., Sands, W. A., Stone, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Reliability+and+validity+of+a+pressure+algometer%5BTitle%5D)+AND+%22J+Strength+Cond+Res%22%5BJournal%5D)">Reliability and validity of a pressure algometer.</a> J Strength Cond Res. 23 (1), 312-314 (2009).</li>
<li>Portney, L. G., Watkins, M. P. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aPortney%2C+LG+%22Foundations+of+Clinical+Research%3A+Applications+to+Practice%22">Foundations of Clinical Research: Applications to Practice</a>. , Prentice Hall. (2009).</li>
</ol>

The authors have nothing to disclose.

我们已经证明具有成本效益的，并且可以用来评估在人受试者机械感，热感和疼痛，以及压疼简单的定性和定量感官测试。这些测定的值是其易于实施和必要的培训时间的低量。每个实验者所接受的训练（一项试验观察和一个试行）少量。因此，多个技术人员可以在一天的培训。结果表明强间实验者和受试者内的可靠性。取决于每个实验使用测试的数量，对于多个IC卡的测试统计校正是可取的。 <...

慢性疼痛是一个世界性的临床问题。全球有超过1.5十亿人患有慢性疼痛，以及全球人口的约5％的神经性疼痛症，与发病率与1年龄的增长。在美国，据估计，疼痛影响比糖尿病，心脏疾病和癌症更多的人，组合2。虽然这个问题的认识正在增加，治疗并不总是成功的，可以是昂贵的，并可能有严重的副作用，包括瘾。研究治疗正在进行中，但作为疼痛的个体之间变化很大，用于研究或诊断疼痛测量可能是有问题。特别是，关于定性方法，如视觉模拟评分（VAS）的依赖，用于确定治疗功效，因为疼痛3的主观和个人性质是有问题的。随着越来越多的研究实验室和世界各地的答案疑问句小诊所关于和治疗疼痛系统蒸发散，是准确的，一致的，可移植的，定量的，和负担得起的措施是很大的需求。 在测量疼痛的关键区别是急性与慢性疼痛。急性疼痛是损伤，感染或其他有害刺激的正常反应。急性疼痛通常与治疗时间解决，疼痛的位置通常是位点特异性的。慢性疼痛，然而，可以进行相关的急性疼痛的初始回合，或者它可以是自发性的。慢性疼痛可能与损伤部位，但它往往是整个身体4普遍。慢性疼痛可以持续数周，数月，甚至数年，对患者及家属，雇主和社会造成重大的生理，心理和金钱的负担。识别和量化疼痛的能力是正确的诊断，持续治疗的评估和新的止痛治疗发展的关键。定量和定性感觉试验是日我们进行诊断和治疗的关键。 几种方法可用于检查外围感觉和疼痛:神经传导速度（NCV），体感诱发电位（SEP），皮肤活检，并定量感官测试（QST）。临床医生也经常使用床边的神经感官检验，但这个测试没有校准，并且不使用一个标准化的指令集5。 NCV和SEP的考试可以是信息，但相比QST，它们需要高度专业化的设备，通常只检查大神经纤维，只测量功能丧失，不测试整个躯体感觉系统6,7。皮肤活检来评估神经纤维密度，但相比QST，它们是侵入性的，并要求组织处理和显微镜的时间，这可能需要几天的时间才能完成8。此外，所述活检仅检查体感系统的一个小的，特定区域和不测试神经功能。 QST测量克服了大多数其他测试方法的局限性。最近，已经进行了QSTs标准化规范的数据可用，这进一步增加了它们的效用，以评估疼痛和神经感觉9-11。因此，我们专注于QST措施慢性疼痛当前协议。 新技术使已建立的内部协议12装备精良的实验室内的疼痛和身体的感觉（如压力和热）精确和可靠的评估。许多这些技术，然而，不容易携带并且是成本过高为新的或小的研究实验室和医疗诊所。此外，对于技术使用的协议不跨越实验室13，其可能会影响可靠性标准化。因此，该手稿的目的是演示有效和可靠的疼痛以及可与设备中可用来进行感官措施大多数诊所或研究实验室。对当前协议的发展的理由是，虽然许多人患有慢性疼痛病症和疼痛的准确评估，需要用于诊断和治疗患有，有与测定的视觉演示没有公布的协议。 用于测试急性疼痛几乎完全自动化的装置的一个例子是神经感官分析仪，它可以可靠地评估热痛觉，由焦虑等人所证明。以下在人类受试者14的皮肤烧伤。单位是模块化的，并且可以添加额外的感官检验设备。在他们的研究中，焦虑等。也说明与使用间断压力传感器，这是定制的压力感官检验。虽然这些探头应该提供更一致的结果，少数的实验室或诊所有他们。 目前的协议表明慢性疼痛QST措施:冯FREý长丝用于皮肤感觉试验，辐射（"哈格里夫斯"的方法），并接触热技术，和压力algometry为深部组织的疼痛。这些QST测量不是唯一的。相反，它们是用于医疗诊所，医院和研究实验室13,15,16人的感官测试中最常见和普遍接受的测量。机械和热的刺激是用来检查皮肤和深感觉。这些措施，此外，包括正常的感觉和疼痛小型和大型纤维灵敏度的评价。为了评估深部组织疼痛（肌肉），压力algometry被使用，这是疼痛的软组织的量化，如肌肉17,18最常应用的技术。这两个A-三角洲和C纤维调解压力刺激19引起的疼痛。两种纤维的刺激是一种优点也是缺点，因为它探讨多种途径，使其成为一个良好的整体措施，但它是一个LSO那么具体。为了检查触摸敏感性，皮肤用的von Frey长丝的机械刺激的使用，因为它们是在疼痛和医疗神经诊所中最常用的感测装置中的一个。冯Frey细丝刺激的Aβ纤维，20但不具体，既低阈值机械感受器，并可以激活21。使用这些细丝一直被人诟病，主要是因为申请程序的潜在变化和关注，机械灯丝特性可能随时间变化22,23（细丝缩进或手部的意外移动度）的。此协议通过提供具有丝的脚本和校准的详细说明解决这些问题。 对于热痛，使用使用"哈格里夫斯"的方法（可见光和斜坡温度）和加热块检查接触热辐射热。联系和辐射热激活热受体不同，甚至可以混淆彼此。它已经显示，动态接触可以抑制热伤害感受24。这类似于热转诊的概念，其中，触摸有助于正常温度感知25-27。因此，热感觉的一种措施，热痛的两项措施都包括在内。首先，辐射热被用来确定（从室温开始）对温度变化的检测的阈值。其次，辐射热源用于确定热痛阈值。暖热变化（非伤害性）的检测部分由对C纤维瞬时受体电位（TRP）通道介导的，而热疼痛是由TRPV1 / V2和上C和A-δ纤维28等较高阈通道介导的-30。在阈值判断，快速加热皮肤先激活A-δ纤维，相当于"第一痛"，其次是一个C纤维介导的"第二痛"descri床为"悸动，燃烧或肿胀"31。暖气给出了C纤维的优惠激活和是第二疼痛32最好的评价。在接触热测定法，恒定伤害性温度被施加到确定定性强度和疼痛的情感方面。 在开发QST协议考虑的另一个变量是解剖学位置。对于急性或特定位置的疼痛，疼痛的解剖部位通常用于测试。由于协议在设计时考虑到慢性疼痛的条件下，我们采取一个更具全球性的做法。协议评估上，而不是手的前臂和腿感觉，因为它已经显示，热疼痛阈值是在手比在前臂33和热伤害感受可以在手被感知显著更高，虽然较不频繁和少强烈比前臂24。而该协议被设计为m个的慢性疼痛病症ajority，我们提醒一些慢性疼痛病症影响特定解剖区域的用户，这应该修改为特定的患者群体的协议时加以考虑。 虽然这些QST措施是最常用的和被接受为一些最可靠的，它们价格便宜，很常见，大多数诊所和研究实验室可能已经访问它们，能买得起他们，并能运送他们。这QST协议是在需要与慢性疼痛人类措施的实验室或诊所有用。迄今为止，目前没有公布可视化报表显示对这些措施的使用性和可靠性的协议。基于此协议的示范和提高可靠性的提示，实验室或诊所可以很容易地审视自己的重测信度。因为许多诊所将需要利用几个技术员来衡量所有的患者，除鼠呃可靠性数据会在选择协议是有用的。我们有一个小的组数据表明，该协议具有良好的可靠性，但每个临床和实验室强烈建议使用此作为一个例子，因为每个诊所和慢性疼痛每个病人的人口是独一无二的。 对感觉和疼痛测试损伤的危险注意事项: 有关皮肤力学性能试验有受伤的危险是极为罕见的，不可能。机械测试是安全的和广泛使用的。风险对个人是最小的，因为1）这是不是一个痛苦或伤害性刺激; 2）科目被指示，他们可以随时停止任何程序，无不良后果; 3）感觉的受试者所经历的水平远低于其耐受程度和阈值的疼痛。 与热痛测试伤害的风险是最小的。热测试是安全的和广泛使用的。虽然热测试确实PRODUCE疼痛，个别风险很小，因为:1）疼痛是一过性的，一般在手术后立即消退; 2）科目被指示，他们可以随时停止任何程序，无不良后果;和3）由受试者经历疼痛的水平低于其耐受水平。与哈格里夫斯热刺激，有接收一燃烧的非常轻微的风险，但是这是由以下最小化:1）阳性的刺激参数高于50℃的锁定; 2）内置的关闭系统时，防止长时间或高强度的刺激（20秒）的递送的刺激;和图3），该前和每次使用过程中测量在玻璃表面的温度的电子式温度计（见下文中的仪器部分）。痛阈试验将进行只有当在20秒截止检测到的温度≤50℃。 有关压力测试的疼痛伤害的风险是最小的。普雷斯确保测试是安全并广泛使用。虽然压力测试不产生疼痛，个别风险很小，因为:1）疼痛是一过性的，一般在手术后立即消退; 2）科目被指示，他们可以随时停止任何程序，无不良后果; 3）疼痛由受试者经历的水平低于其公差水平; 4）施加的疼痛是从未比检者的痛苦阈值时，这远远低于可能导致损害的任何压力以上。压力测试的一个罕见的副作用的刺激部位擦伤。在这种情况下，受试者不应该在压伤现场重新测试。易怒的机会可以通过很容易碰伤或正在服用血液稀释剂的个人研究排斥最小化。 在登记期间，参与者给出的将要使用的所有的感觉和疼痛的措施的完整说明。与最初的同意，所有参与者都异体结婚满入学前体验所有的感官和疼痛的措施。所有感觉和疼痛测定法基于在健康人类受试者和慢性疼痛的患者34使用既定测定。所有检测涉及要么无害（无疼痛刺激）或急性伤害性刺激（疼痛刺激）不损伤组织。不同的测试之间的时间&gt; 5分钟，以允许受试者休息并减少感觉疲劳或致敏的可能。测试的顺序是每次测试期间相同。测试的具体位点仅限于左和右前臂和L3 / S2皮上的左，右小腿T1的皮。所有站点进行测试都标有一个标记，各个网站的传播出去，以避免重叠感受野激活（ 图1）。请参阅材料和设备表的完整材料清单。对于重测信度研究，个别科目我们再由两个实验者在一天的测试。

<table><tbody><tr><td>Pressure Algometer/Force Dial</td><td>Wagner Instruments</td><td>FDK 20</td><td>The pressure algometer quantifies pressure pain threshold. It has a rubber tip attachment that is applied to the marked skin site by the investigator. The dial records the pressure and is reset after each measurement.</td></tr><tr><td>von Frey cutaneous stimulators</td><td>Touch Test</td><td>NC1275-01 through -08</td><td>These von Frey filaments are commonly used to examine sensitivity in research and clinical settings. Our set of 8 filaments covers a range of sensitivities. The individual filaments are 1.65 mN, 2.36 mN, 2.44 mN, 2.83 mN, 3.22 mN, 3.61 mN, 3.84 mN, 4.08 mN.</td></tr><tr><td>&quot;Hargreaves&quot; apparatus, testing platform</td><td>Custom</td><td>n/a</td><td>One complete base and four supporting columns are used to form a platform for a sheet of safety glass through which the heat source directs heat to the subjects arm or leg that is resting on the glass. The heat lamp is placed beneath the glass.</td></tr><tr><td>0.64 cm Pyrex safety glass</td><td>DuPont</td><td>n/a</td><td>Safety glass is important to avoid injury in the unlikely event of a fracture in the glass surface.</td></tr><tr><td>Electronic thermometer/thermocouple 53 IIB</td><td>Fluke</td><td>3821062</td><td>The thermocouple is used for thermal testing. The thermocouple is placed on the glass underneath the subject&#039;s arm or leg and measures the temperature at the glass level.</td></tr><tr><td>IITC Plantar Analgesia Meter&amp;nbsp;</td><td>Life Science Inc. Woodland Hills, CA</td><td>390</td><td>This is the heat source and timer for Hargreaves testing. The unit&#039;s heat source has an &amp;ldquo;idle state&amp;rdquo; that allows exact placement of the heat source. The heat source is radiant light and the light beam is focused to the top of the glass to creates a 4 mm x 6 mm intense spot on the arm or leg.</td></tr><tr><td>Examiner script</td><td>Custom</td><td>n/a</td><td>A written script for the examiner is used for every testing session. Because pain and sensitivity can be affected by environmental stresses, we attempt to maintain as much consistency as possible between subjects. The examiner reads directly from the script every time a measure is made to ensure verbal consistency.</td></tr><tr><td>Markers for testing site</td><td>Sharpie</td><td>n/a</td><td>Washable markers may be preferable for situations where multiple days of testing is not necessary</td></tr><tr><td>Constant heat stimulus block</td><td>Benchmark Scientific</td><td>BR10-00</td><td>This block is digitally controlled. The surface of the block is 2 cm x 3 cm.</td></tr></tbody></table>

a protocol of manual tests to measure sensation and pain in humans

众多的定性和定量技术可用于测试在研究和临床环境感觉神经和疼痛。目前的研究表明用技术来衡量使用便携式和容易地访问设备的压力和热量触觉和痛觉阈值定量感官测试协议。这些技术和设备非常适合新的实验室和诊所的成本是一个问题或一个限制因素。我们演示了以下测量技术:在胳膊和腿（冯弗雷细丝），辐射和接触热灵敏度（与两个阈值和使用视觉模拟评分（VAS）定性评估）和机械压力的敏感性皮肤的机械灵敏度（痛觉计，与两个阈值和增值业务）。该技术和设备描述和演示在这里可以很容易地购买，储存，并通过世界各地的大多数诊所和研究实验室运输。一个limitati这种方法的缺乏自动化或电脑控制。因此，这些方法可在人员训练和数据记录不是更复杂的设备方面更多的劳动密集的。我们提供了一组用于展示技术的可靠性数据。从我们的描述，一个新的实验室应该能够建立和运行这些测试和开发自己的内部可靠性数据。

这里，我们描述了具有成本效益的定性和定量的分析的执行来测量使用VAS（ 图2）人类受试者无害的感觉和疼痛。视觉表示是非常重要的，因为这些检查的准确和精确的结果取决于由技术人员正确和一致的协议执行。此外，这是有价值的知道，如果所描述的可以收集再生的数据的多个技术人员执行的技术。虽然这不是本研究的意图完成一个全面的可靠性分析（...

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

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

手动测试的协议来衡量感觉和疼痛人类

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

a-protocol-of-manual-tests-to-measure-sensation-and-pain-in-humans

Research

JoVE Journal

Behavior

20.9K 次观看.  Duquesne University. The goal of this procedure is to demonstrate a battery of quantitative techniques for sensory and pain measurement in humans. The equipment and techniques described are commonly found in pain clinics or are easy to obtain.

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

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

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 ...

行为学

Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the intra-individual sensation magnitude that is evoked by stimulation over multiple trials. This requires a robust mapping of stimulus magnitude to perceived intensity and is commonly achieved by psychophysical estimation methods such as the staircase procedure. Newer, more efficient procedures like the QUEST algorithm fit a psychophysical function to the data in real time while at the same time maximizing the efficiency of data collection. A robust estimate of the threshold intensity between painful and nonpainful perceptions can then be used to reduce the influence of variations in sensory input in subsequent analyses of oscillatory brain activity. By stimulating at a constant threshold intensity determined by an adaptive estimation procedure, the variance in the ratings can be directly attributed to perceptual processes. Oscillatory activity can then be contrasted between &#34;pain&#34; and &#34;no-pain&#34; trials directly, yielding activity that closely relates to perceptual classification processes in nociception.

Psychophysical methods such as the QUEST estimation procedure can efficiently yield robust estimates of the stimulation intensity at which nonpainful sensations transition into painful sensations. By stimulating repeatedly at the threshold intensity, the variability in rating responses can directly be attributed to perceptual classifications in subsequent analyses.

在研究疼痛相关振荡Prestimulus活动偏侧Psychophysically锚，乐百氏阈值

In perceptual studies, it is often important to objectively assess the equality of delivered stimulation across participants or to quantify the ...

Determining heat and mechanical pain threshold in inflamed skin of human subjects

In a previous article in the Journal of Visualized Experiments we have demonstrated skin microdialysis techniques for the collection of tissue-specific nociceptive and inflammatory biochemicals in humans. In this article we will show pain-testing paradigms that are often used in tandem with microdialysis procedures. Combining pain tests with microdialysis provides the critical link between behavioral and biochemical data that allows identifying key biochemicals responsible for generating and propagating pain.
Two models of evoking pain in inflamed skin of human study participants are shown. The first model evokes pain with aid of heat stimuli. Heat evoked pain as described here is predominantly mediated by small, non-myelinated peripheral nociceptive nerve fibers (C-fibers). The second model evokes pain via punctuated pressure stimuli. Punctuated pressure evoked pain is predominantly mediated by small, myelinated peripheral nociceptive nerve fibers (A-delta fibers). The two models are mechanistically distinct and independently examine nociceptive processing by the two major peripheral nerve fiber populations involved in pain signaling.
Heat pain is evoked with aid of the TSA II, a commercially available thermo-sensory analyzer (Medoc Advanced Medical Systems, Durham, NC). Stimulus configuration and delivery is handled with aid of specific software. Thermodes vary in size and shape but in principle consist of a metal plate that can be heated or cooled at various rates and for different periods of time. Algorithms assessing heat-evoked pain are manifold. In the experiments shown here, study participants are asked to indicate at what point they start experiencing pain while the thermode in contact with skin is heated at a predetermined rate starting at a temperature that does not evoke pain. The thermode temperature at which a subject starts experiencing pain constitutes the heat pain threshold.
Mechanical pain is evoked with punctuated probes. Such probes are commercially available from several manufacturers (von Frey hairs). However, the accuracy of von Frey hairs has been criticized and many investigators use custom made punctuated pressure probes. In the experiments shown here eight custom-made punctuated probes of different weights are applied in consecutive order, a procedure called up-down algorithm, to identify perceptional deflection points, i.e., a change from feeling no pain to feeling pain or vice versa. The average weight causing a perceptional deflection constitutes the mechanical pain threshold.

Algorithms assessing heat and mechanical pain thresholds in experimentally inflamed skin of human study subjects are shown. The two pain testing paradigms independently examine nociceptive processing by the two major peripheral nerve fiber populations transmitting pain, i.e., non-myelinated C fibers and small myelinated A-delta fibers.

确定人类受试者皮肤发炎的热和机械痛阈

In a previous article in the Journal of Visualized Experiments we have demonstrated skin microdialysis techniques for the collection of tissue-specific ...

生物学

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

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

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

分析疼痛对热和电刺激反应的多模态信号

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

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen,&#160;or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models.

Electronic von Frey measurements are an effective and improved alternative to classical von Frey filaments, as they allow rapid and precise measurement of changes in rodent mechanical withdrawal thresholds to continuously applied pressure stimuli before and after an inflammatory event.

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain ...

神经科学

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

Low back pain is the leading cause of disability worldwide, with dramatic personal, economic, and social consequences. To develop novel therapeutics, animal models are needed to examine the mechanisms and effectiveness of novel therapies from a translational perspective. Several rodent models of back pain are used in current investigations. Surprisingly, however, no standardized behavioral test was validated to assess mechanical sensitivity in back pain models. This is critical to confirm that animals with presumed back pain present local hypersensitivity to nociceptive stimuli, and to monitor sensitivity during interventions designed to relieve back pain. The objective of this study is to lay down a simple and accessible test to assess mechanical sensitivity in the back of rats. A test cage was fabricated specifically for this method; length x width x height: 50 x 20 x 7 cm, having a stainless-steel mesh on the top. This test cage allows the application of mechanical stimuli to the back. To perform the test, the back of the animal is shaved in the region of interest, and the test area is marked to repeat the test on different days, as needed. The mechanical threshold is determined with Von Frey filaments applied to the paraspinal muscles, utilizing the up-down method described previously. The positive responses include (1) muscle twitching, (2) arching (back extension), (3) rotation of the neck (4) scratching or licking the back, and (5) escaping. This behavioral test (Back Mechanical Sensitivity (BMS) test) is useful for mechanistic research with rodent models of back pain for the development of therapeutic interventions for the prevention and management of back pain.

To develop novel therapeutic interventions for the prevention and management of back pain, animal models are required to examine the mechanisms and effectiveness of these therapies from a translational perspective. The present protocol describes the BMS test, a standardized method to assess back mechanical sensitivity in the rat.

大鼠背部机械敏感性评估用于慢性背痛的机制研究

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

Dynamic Quantitative Sensory Testing to Characterize Central Pain Processing

Central facilitation and modulation of incoming nociceptive signals play an important role in the perception of pain. Disruption in central pain processing is present in many chronic pain conditions and can influence responses to specific therapies. Thus, the ability to precisely describe the state of central pain processing has profound clinical significance in both prognosis and prediction. Because it is not practical to record neuronal firings directly in the human spinal cord, surrogate behavior tests become an important tool to assess the state of central pain processing. Dynamic QST is one such test, and can probe both the ascending facilitation and descending modulation of incoming nociceptive signals via TS and CPM, respectively. Due to the large between-individual variability in the sensitivity to noxious signals, standardized TS and CPM tests may not yield any meaningful data in up to 50% of the population due to floor or ceiling effects. We present methodologies to individualize TS and CPM so we can capture these measures in a broader range of individuals than previously possible. We have used these methods successfully in several studies at the lab, and data from one ongoing study will be presented to demonstrate feasibility and potential applications of the methods.

By assessing pain in response to repetitive or different types of standardized stimuli, dynamic quantitative sensory testing (QST) can reveal changes in the central processing of pain. We present methods to optimize and individualize two dynamic QST measures: temporal summation (TS) and conditioned pain modulation (CPM).

动态定量感觉测试表征中央疼痛处理

Central facilitation and modulation of incoming nociceptive signals play an important role in the perception of pain. Disruption in central pain ...

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

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

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 ...

Assessment of Sensory Thresholds in Dogs Using Mechanical and Hot Thermal Quantitative Sensory Testing

Quantitative sensory testing (QST) is used to evaluate the function of the somatosensory system in dogs by assessing the response to applied mechanical and thermal stimuli. QST is used to determine normal dogs&#39; sensory thresholds and evaluate alterations in peripheral and central sensory pathways caused by various disease states, including osteoarthritis, spinal cord injury, and cranial cruciate ligament rupture. Mechanical sensory thresholds are measured by electronic von Frey anesthesiometers and pressure algometers. They are determined as the force at which the dog exhibits a response indicating conscious stimulus perception. Hot thermal sensory thresholds are the latency to respond to a fixed or ramped temperature stimulus applied by a contact thermode.
Following a consistent protocol for performing QST and paying attention to details of the testing environment, procedure, and individual study subjects are critical for obtaining accurate QST results for dogs. Protocols for the standardized collection of QST data in dogs have not been described in detail. QST should be performed in a quiet, distraction-free environment that is comfortable for the dog, the QST operator, and the handler. Ensuring that the dog is calm, relaxed, and properly positioned for each measurement helps produce reliable, consistent responses to the stimuli and makes the testing process more manageable. The QST operator and handler should be familiar and comfortable with handling dogs and interpreting dogs&#39; behavioral responses to potentially painful stimuli to determine the endpoint of testing, reduce stress, and maintain safety during the testing process.

This work describes a standard protocol for mechanical and hot thermal quantitative sensory testing to evaluate the somatosensory system in dogs. Sensory thresholds are measured using an electronic von Frey anesthesiometer, pressure algometer, and hot contact thermode.

使用机械和热热定量感官测试评估狗的感官阈值

Quantitative sensory testing (QST) is used to evaluate the function of the somatosensory system in dogs by assessing the response to applied mechanical ...