Pain Mechanisms and the Development of Analgesics

描述(由申请人提供)： 疼痛及其控制被认为是一个主要的医学问题。在过去的20年里，我们对导致疼痛状态的信息的处理机制的理解取得了重大进展。尽管对复杂的药理学有这些实质性的见解，但将机械数据转换为临床相关药物一直是乏味的。 人们认识到了几个问题。首先，人们认识到，一个重要的问题涉及对临床前行为模型的解释，以预测人类的疗效，以及特定的模型是否足以预测不同疼痛状态下的结果。其次，人们认为，人体实验模型将在药物开发过程的早期提供对疗效的重要见解，但这些模型的验证一直很困难。 会议将首先审查目前对急性刺激、组织损伤和神经损伤产生的信息以呈现疼痛状态的方式进行编码的机制的想法。其次，对呈现有害事件行为表达的临床前替代模型进行综述，并对跨模型一致性和可靠性进行综述。第三，我们将回顾在人类志愿者中提供临床前定义的疼痛机制相关性的实验人类模型，并考虑它们预测病理状态下药物活性的能力。最后，演讲者将回顾人类试验的实施情况，这些试验确定了药物疗法的止痛效果。这4个组成部分的一个重要方面是经常实施基于病例的平行，反映预测的成功(例如COX2抑制剂、加巴喷丁、齐康肽)和失败(NK1拮抗剂)。

DESCRIPTION (provided by applicant): Pain and its control are appreciated to be a major medical problem. Over the past 20 years there have been major advances in our understanding of the mechanisms by which information leading to a pain state is processed. In spite of these substantial insights into the complex pharmacology, the translation of mechanistic data into clinically relevant drugs has been tedious. Several problems are recognized. First, it is recognized that an important problem relates to the interpretation of the preclinical behavioral models as to predicting human efficacy and whether specific models adequately predict outcomes in different pain states. Second, it is believed that the human experimental model would provide important insights into efficacy early in the drug development process, but validation of these models has been difficult. The meeting will first review the current thinking regarding the mechanisms whereby information generated by acute stimulation, tissue injury and nerve injury are encoded in a manner so as to present a pain state. Secondly, the preclinical surrogate models which present the behavioral expression of the noxious event will be reviewed and cross model consistency and reliability will be reviewed. Thirdly, we will review the experimental human models that provide a correlate in human volunteers of the preclinically defined pain mechanisms and consider their ability to predict drug activity in pathological states. Finally, presenters will review the implementation of human trials which define the analgesic efficacy of drug therapies. An important aspect of these 4 components is the frequent implementation of case based parallels that reflect successes in prediction (e.g. COX2 inhibitors, GABApentin, ziconotide) and failures (NK1 antagonist).