Cooper Stephen A, Desjardins Paul J
Senior VP Clinical and Medical Affairs (retired), Palm Beach Gardens, FL, USA.
Methods Mol Biol. 2010;617:175-90. doi: 10.1007/978-1-60327-323-7_15.
The modern version of the Dental Impaction Pain Model (DIPM) was developed in the mid-1970s. Since that time, several hundred studies have been conducted by numerous investigators. Today it is arguably the most utilized of all the acute pain models. Its popularity is due to the success rate of the studies, fast subject entry, and cost effectiveness. The surgical procedure is extremely standardized, and the surgery requires either minimal or no use of CNS depressant anesthetics. The methodology is similar to that utilized in other acute pain models; however, the DIPM is much more versatile than most other models. The model can be easily adapted to perform multiple-dose studies, pharmacokinetics/pharmacodynamics (PK/PD) correlations, preemptive interventions, and sleep-pain studies. A few investigators have even developed microdialysis techniques, wherein they insert probes into extraction sockets to collect exudates for measuring biochemical mediators of pain or drug levels at the site of injury. In many instances, an accomplished site can complete a study of several hundred subjects in approximately 3 months. There are studies in the literature that have incorporated up to six treatment arms in one study and clearly separated the drugs from each other. The exquisite assay sensitivity is due to the homogeneity of the study population, the predictable level and appropriate intensity of the postsurgical pain, and the minimizing of variability by using only one or two study centers. The DIPM has been employed to evaluate NSAIDs (both nonselective and selective Cox inhibitors), opioids and combination analgesics, as well as some investigational drugs with unique mechanisms of action. The model is particularly useful for proof-of-concept studies that require dose-ranging and profiling the time-effect curve for efficacy including onset, peak effect, and duration of analgesic activity.
现代版的牙阻生疼痛模型（DIPM）是在20世纪70年代中期开发的。自那时以来，众多研究人员进行了数百项研究。如今，它可以说是所有急性疼痛模型中使用最广泛的。其受欢迎程度得益于研究的成功率、受试者快速入组以及成本效益。手术过程极其标准化，手术要么极少使用中枢神经系统抑制性麻醉剂，要么根本不使用。该方法与其他急性疼痛模型所采用的方法类似；然而，DIPM比大多数其他模型的用途要广泛得多。该模型可以轻松调整以进行多剂量研究、药代动力学/药效学（PK/PD）相关性研究、预防性干预研究以及睡眠-疼痛研究。一些研究人员甚至开发了微透析技术，即他们将探针插入拔牙窝以收集渗出液，用于测量损伤部位疼痛的生化介质或药物水平。在许多情况下，一个成熟的研究地点大约可以在3个月内完成对数百名受试者的研究。文献中有一些研究在一项研究中纳入了多达六个治疗组，并将药物彼此清晰区分。其出色的检测灵敏度归因于研究人群的同质性、术后疼痛可预测的程度和适当的强度，以及仅使用一两个研究中心来尽量减少变异性。DIPM已被用于评估非甾体抗炎药（非选择性和选择性环氧化酶抑制剂）、阿片类药物和复方镇痛药，以及一些具有独特作用机制的研究性药物。该模型对于概念验证研究特别有用，这些研究需要确定剂量范围并描绘疗效的时间-效应曲线，包括起效时间、峰值效应和镇痛活性持续时间。
