Pain Mechanisms and the Development of Analgesics

疼痛机制和镇痛药的发展

• 批准号: 7114565
• 负责人: TONY L. YAKSH
• 金额: $ 1.5万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114565
• 关键词: analgesics; meeting /conference /symposium; neuropharmacology; travel

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).

描述（由申请人提供）： 疼痛及其控制是一个主要的医疗问题。在过去的20年中，我们了解导致疼痛状态的信息的机制取得了重大进展。尽管对复杂药理学有实质性的见解，但将机械数据转化为临床相关的药物仍然很乏味。 认识到几个问题。首先，人们认识到，一个重要的问题与临床前行为模型的解释有关，即预测人类功效以及特定模型是否可以充分预测不同疼痛状态的结果。其次，人们认为人类的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，但是对这些模型的验证很困难。 会议将首先回顾有关急性刺激，组织损伤和神经损伤产生的机制的当前思维，以某种方式编码以表达疼痛状态。其次，将审查呈现有害事件行为表达的临床前替代模型，并将审查跨模型的一致性和可靠性。第三，我们将回顾一下在临床上定义的疼痛机制的人类志愿者中提供相关性的实验人类模型，并考虑其预测病理状态药物活性的能力。最后，演示者将审查人类试验的实施，该试验定义了药物疗法的镇痛功效。这4个组成部分的一个重要方面是经常实施基于病例的相似之处，这些相似之处反映了预测成功（例如Cox2抑制剂，加巴喷丁，Ziconotide）和失败（NK1拮抗剂）。