Staahl Camilla, Reddy Hariprasad, Andersen Søren Due, Arendt-Nielsen Lars, Drewes Asbjørn Mohr
Center for Visceral Biomechanics and Pain, Department of Gastroenterology, University Hospital Aalborg, Denmark.
Basic Clin Pharmacol Toxicol. 2006 Feb;98(2):201-11. doi: 10.1111/j.1742-7843.2006.pto_211.x.
Experimental pain models for assessment of analgesic effect needs to be reproducible, valid and responding in a uniform way to changes in pain level. The pain system differs in various tissue types and analgesics may have different effects in different tissues. This study assessed the reproducibility of an experimental model using mechanical, thermal and electrical stimulations. Pain was evoked in three tissues: Skin, muscle and viscera. Pain was evoked and assessed in 24 healthy volunteers. The experiment was repeated three times with 30 min. intervals and twice with a weekly interval. Systematic bias, intra-class correlation (ICC) and coefficient of variation (CV) and valid sample sizes for analgesic testing were assessed. The model proved to be feasible. Most tests were unbiased, showing stable means except for the mechanical and thermal stimulation in viscera, which showed decreasing pain thresholds when the tests were repeated with 30 min. intervals. Generally the pain tests showed relatively high CV (mean 71%, range 8-145%). The pain tests showed high ICC's (>0.80) when repeated on the same day. When the tests were repeated with an interval of one week, ICC was smaller (mean 0.79 range 0.49-0.96). This means that these tests are useful for analgesic testing recruiting useful sample sizes in a crossover (mean 31 range 2-84) and a parallel study (mean 59 range 3-164) design. Application of this experimental pain model in a cross-over study design with appropriate base-line recordings offers a unique opportunity of revealing analgesic effects on pain arising from different tissues.
用于评估镇痛效果的实验性疼痛模型需要具有可重复性、有效性，并且能以统一的方式对疼痛水平的变化做出反应。疼痛系统在不同组织类型中存在差异，并且镇痛药在不同组织中可能具有不同的作用。本研究使用机械、热和电刺激评估了一种实验模型的可重复性。在三种组织中诱发疼痛：皮肤、肌肉和内脏。在24名健康志愿者身上诱发并评估疼痛。实验以30分钟的间隔重复进行三次，以每周的间隔重复进行两次。评估了系统偏差、组内相关系数（ICC）和变异系数（CV）以及用于镇痛测试的有效样本量。该模型被证明是可行的。大多数测试无偏差，除了内脏的机械和热刺激外，均值稳定，当以30分钟的间隔重复测试时，内脏的疼痛阈值降低。一般来说，疼痛测试显示出相对较高的CV（平均71%，范围8 - 145%）。当在同一天重复进行时，疼痛测试显示出较高的ICC（>0.80）。当以一周的间隔重复测试时，ICC较小（平均0.79，范围0.49 - 0.96）。这意味着这些测试对于在交叉设计（平均31，范围2 - 84）和平行研究设计（平均59，范围3 - 164）中招募有用样本量的镇痛测试是有用的。在具有适当基线记录的交叉研究设计中应用这种实验性疼痛模型，为揭示镇痛药对不同组织产生的疼痛的作用提供了独特的机会。
