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健康受试者中局部辣椒素应用引起的神经病理性疼痛模式。

Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.

机构信息

Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine and Pharmacology TMP, Frankfurt am Main, Germany DataBionics Research Group, University of Marburg, Marburg, Germany.

出版信息

Pain. 2015 Mar;156(3):405-414. doi: 10.1097/01.j.pain.0000460328.10515.c9.

Abstract

Human experimental pain models are widely used to study drug effects under controlled conditions, but they require further optimization to better reflect clinical pain conditions. To this end, we measured experimentally induced pain in 110 (46 men) healthy volunteers. The quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain) was applied on untreated ("control") and topical capsaicin-hypersensitized ("test") skin. Z-transformed QST-parameter values obtained at the test site were compared with corresponding values published from 1236 patients with neuropathic pain using Bayesian statistics. Subjects were clustered for the resemblance of their QST pattern to neuropathic pain. Although QST parameter values from the untreated site agreed with reference values, several QST parameters acquired at the test site treated with topical capsaicin deviated from normal. These deviations resembled in 0 to 7 parameters of the QST pattern observed in patients with neuropathic pain. Higher degrees (50%-60%) of resemblance to neuropathic QST pattern were obtained in 18% of the subjects. Inclusion in the respective clusters was predictable at a cross-validated accuracy of 86.9% by a classification and regression tree comprising 3 QST parameters (mechanical pain sensitivity, wind-up ratio, and z-transformed thermal sensory limen) from the control sites. Thus, we found that topical capsaicin partly induced the desired clinical pattern of neuropathic pain in a preselectable subgroup of healthy subjects to a degree that fuels expectations that experimental pain models can be optimized toward mimicking clinical pain. The subjects, therefore, qualify for enrollment in analgesic drug studies that use highly selected cohorts to enhance predictivity for clinical analgesia.

摘要

人体实验性疼痛模型广泛用于在受控条件下研究药物作用,但需要进一步优化,以更好地反映临床疼痛状况。为此,我们对 110 名(46 名男性)健康志愿者进行了实验性诱导疼痛测量。应用定量感觉测试(QST)电池(德国神经性疼痛研究网络)对未经处理的(“对照”)和局部辣椒素超敏化的(“测试”)皮肤进行测试。在测试部位获得的 QST 参数的 Z 变换值与使用贝叶斯统计从 1236 名神经性疼痛患者获得的相应值进行了比较。根据 QST 模式与神经性疼痛的相似程度对受试者进行了聚类。尽管未处理部位的 QST 参数值与参考值相符,但在局部应用辣椒素处理的测试部位获得的几个 QST 参数值偏离了正常值。这些偏差与神经性疼痛患者观察到的 QST 模式的 0 到 7 个参数相似。在 18%的受试者中,观察到与神经性 QST 模式的相似程度更高(50%-60%)。通过包括 3 个来自对照部位的 QST 参数(机械疼痛敏感性、上冲比和 z 变换热感觉阈值)的分类和回归树,在交叉验证的准确率为 86.9%的情况下,可预测受试者纳入各自的聚类。因此,我们发现,在可预先选择的健康受试者亚组中,局部辣椒素在一定程度上诱导了预期的神经性疼痛临床模式,这增加了对实验性疼痛模型能够朝着模拟临床疼痛进行优化的期望。因此,这些受试者有资格参加使用高度选择队列来增强对临床镇痛预测性的镇痛药物研究。

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