Pain Mechanisms and the Development of Analgesics

Keystone Symposia, Silverthorne CO

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] 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. [unreadable] [unreadable] 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. [unreadable] [unreadable] 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). [unreadable] [unreadable] [unreadable]