Faculty of Medicine, McGill University, Montreal, QC, Canada.
The Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada.
Eur J Pain. 2018 Feb;22(2):370-384. doi: 10.1002/ejp.1126. Epub 2017 Oct 6.
Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted.
In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal. Two experiments in healthy participants were performed for model characterization. In Experiment 1, a constant temperature was applied for 60 min; in Experiment 2, temperature was adjusted to maintain a constant perceived intensity for 60 min.
Experiment 1: across participants, constant temperature induced initial habituation followed by an increase in sensation back to baseline. Cluster analysis revealed that half the participants sensitized to the constant temperature, while the other half did not. The degree of sensitization was related to the baseline pain unpleasantness, relative to pain intensity. Experiment 2: constant perceived intensity was achieved in the painful and a non-painful control condition. The two conditions did not differ regarding possibly confounding variables, including blood pressure, heart rate, inflammation or physiological stress as measured by surrogate markers. Secondary allodynia and hyperalgesia were reported more following painful compared to control stimulation. Sensitizers as determined in Experiment 1 were also more pain sensitive in Experiment 2.
The CHOP model reproduces some aspects of clinical pain, such as longer duration, sensitization, secondary allodynia and hyperalgesia.
Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top-down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions.
人体实验性疼痛模型为临床疼痛的临床前模型提供了重要的转化联系。使用局部辣椒素和持续热应用，新型辣椒素/热持续疼痛（CHOP）模型可引起持久的实验性疼痛，其感知强度可单独调节。
在 CHOP 模型中，将辣椒素或对照乳膏涂于 10×10cm 的皮肤区域，乳膏去除后在该区域上放置加热垫。在健康参与者中进行了两项实验以对模型进行特征描述。在实验 1 中，应用恒定温度 60min；在实验 2 中，调整温度以保持 60min 的恒定感知强度。
实验 1：在所有参与者中，恒定温度引起初始习惯化，然后感觉增加回到基线。聚类分析表明，一半的参与者对恒定温度敏感，而另一半则没有。敏感化的程度与基线疼痛不愉快度有关，相对于疼痛强度。实验 2：在疼痛和非疼痛对照条件下实现了恒定的感知强度。这两种情况在可能的混杂变量方面没有差异，包括通过替代标志物测量的血压、心率、炎症或生理应激。与对照刺激相比，报告更多的继发痛觉过敏和痛觉过敏。在实验 1 中确定的敏感化者在实验 2 中也对疼痛更敏感。
CHOP 模型再现了一些临床疼痛的特征，例如持续时间较长、敏感化、继发痛觉过敏和痛觉过敏。
在这里，我们展示了一种新的疼痛模型，该模型可以在没有组织损伤的情况下应用长达一小时。CHOP 模型允许研究原发性和继发性痛觉过敏以及对敏感化的自上而下影响，从而提供了一种可用于评估以临床为导向的问题的实验模型。
