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）： 疼痛及其控制被认为是一个主要的医学问题。过去 20 年来，我们对导致疼痛状态的信息处理机制的理解取得了重大进展。尽管对复杂的药理学有了这些实质性的见解，但将机制数据转化为临床相关药物仍然很乏味。 认识到几个问题。首先，人们认识到一个重要问题涉及临床前行为模型的解释，以预测人类功效以及特定模型是否足以预测不同疼痛状态下的结果。其次，人们相信人体实验模型将为药物开发过程早期的疗效提供重要的见解，但这些模型的验证一直很困难。 会议将首先回顾目​​前关于急性刺激、组织损伤和神经损伤产生的信息以某种方式编码以呈现疼痛状态的机制的想法。其次，将审查呈现有害事件行为表达的临床前替代模型，并审查跨模型的一致性和可靠性。第三，我们将回顾实验人体模型，这些模型为人类志愿者提供了临床前定义的疼痛机制的相关性，并考虑它们预测病理状态下药物活性的能力。最后，演讲者将回顾人体试验的实施情况，这些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频繁实施基于案例的平行分析，反映预测的成功（例如 COX2 抑制剂、GABA喷丁、齐考诺肽）和失败（NK1 拮抗剂）。