Web Desc
Pain Mechanisms and the Development of Analgesics
Organizer(s): Tony L. Yaksh, Mitchell B. Max, James C. Eisenach, Patrick W. Mantyh and Frank Porreca
Date: June 11 - 16, 2006
Location: Keystone Resort, Keystone, CO, USA
Supported by The Director's Fund
Summary of Meeting:
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, an important problem relates to the interpretation of the preclinical behavioral models with respect 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 this model 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).
Scholarship Deadline: February 9 2006
Discounted Abstract Deadline: February 9 2006
Abstract Deadline: April 11 2006
Discounted Registration Deadline: April 11 2006
We gratefully acknowledge additional support for this conference from:
AstraZeneca R&D MontréalEducational donation provided by AmgenNovartis Institutes for BioMedical Research
We gratefully acknowledge additional in-kind support for this conference from those foregoing speaker expense reimbursements:

Merck & Co., Inc.

Pfizer Inc.

Progenics Pharmaceuticals, Inc.

Wyeth Consumer Healthcare

Wyeth Pharmaceuticals
We gratefully acknowledge the generous grant for this conference provided by:

National Institute on Drug Abuse (NIDA)
Grant No. 1R13 DA021484-01
We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:

Click here to view more of these organizations
Special thanks to the following for their support of Keystone Symposia initiatives to increase participation at this meeting by scientists from underrepresented backgrounds:

Click here to view more of these organizations

Program

Sunday, June 11 | 3:00PM - 7:30PM
Registration
Room: Gallery


Sunday, June 11 | 6:30PM - 7:30PM
Refreshments
Room: Gallery & Lakeside Suite


Sunday, June 11 | 7:30PM - 8:30PM
Keynote Address
Room: Arapahoe

Speaker 1 of 1
Mitchell B. Max, University of Pittsburgh, Center for Pain Research, USA
Dissecting Chronic Pain Syndromes as Complex Genetic Disorders

Monday, June 12 | 7:00AM - 8:00AM
Breakfast
Room: Bighorn/Champeaux


Monday, June 12 | 8:00AM - 11:00AM
Pharmacology of Pain Encoding I... Rational Targets of Analg
esic Development

Room: Arapahoe

Speaker 1 of 4
* James C. Eisenach, Wake Forest University School of Medicine, USA

Monday, June 12 | 8:00AM - 11:00AM
Pharmacology of Pain Encoding I... Rational Targets of Analg
esic Development

Room: Arapahoe

Speaker 2 of 4
Jon Levine, University of California, San Francisco, USA
Pain Mechanisms and the Development of Analgesics: Target Practice

Monday, June 12 | 8:00AM - 11:00AM
Pharmacology of Pain Encoding I... Rational Targets of Analg
esic Development

Room: Arapahoe

Speaker 3 of 4
Clifford J. Woolf, Children's Hospital, USA
Facilitatory Cascades in Post Injury States

Monday, June 12 | 8:00AM - 11:00AM
Pharmacology of Pain Encoding I... Rational Targets of Analg
esic Development

Room: Arapahoe

Speaker 4 of 4
Stephen B. McMahon, King's College London, UK
CCL2 as a Mediator of Neuropathic Pain

Monday, June 12 | 9:20AM - 9:40AM
Coffee Break
Room: Gallery & Lakeside Suite


Monday, June 12 | 11:00AM - 1:00PM
Poster Setup
Room: Divide/Ten Mile


Monday, June 12 | 1:00PM - 10:00PM
Poster Viewing
Room: Divide/Ten Mile


Monday, June 12 | 2:30PM - 4:30PM
Workshop 1
Room: Arapahoe
1) Cascades upon cascades.. does any one of them really matter? 2) Is neuropathic pain after peripheral nerve injury a question of persistent afferent traffic? 3) The sprouting axon, afferents to sympathetics in nerve injury induced pain states. 4) What makes a terminal discharge after local tissue inflammation? 5) Where is the convergence between tissue and nerve injury pain mechanisms? 6) The hottest target: left vs right brain choices?
Speaker 1 of 2
* James C. Eisenach, Wake Forest University School of Medicine, USA

Monday, June 12 | 2:30PM - 4:30PM
Workshop 1
Room: Arapahoe
1) Cascades upon cascades.. does any one of them really matter? 2) Is neuropathic pain after peripheral nerve injury a question of persistent afferent traffic? 3) The sprouting axon, afferents to sympathetics in nerve injury induced pain states. 4) What makes a terminal discharge after local tissue inflammation? 5) Where is the convergence between tissue and nerve injury pain mechanisms? 6) The hottest target: left vs right brain choices?

Short Talk(s) Chosen from Abstracts

Monday, June 12 | 4:30PM - 5:00PM
Coffee Available
Room: Gallery & Lakeside Suite


Monday, June 12 | 5:00PM - 7:00PM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? I

Room: Arapahoe

Speaker 1 of 4
* James C. Eisenach, Wake Forest University School of Medicine, USA

Monday, June 12 | 5:00PM - 7:00PM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? I

Room: Arapahoe

Speaker 2 of 4
Timothy Brennan, University of Iowa, USA
Acute-Postoperative Pain

Monday, June 12 | 5:00PM - 7:00PM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? I

Room: Arapahoe

Speaker 3 of 4
Frank Porreca, University of Arizona, USA
Peripheral and Central Sensitization in Chronic Pain of Osteoarthritis and Rheumatoid Arthritis

Monday, June 12 | 5:00PM - 7:00PM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? I

Room: Arapahoe

Speaker 4 of 4
Theo F. Meert, Johnson & Johnson Pharmaceutical Research & Development, LLC, Belgium
Nerve Injury Models

Monday, June 12 | 7:00PM - 8:00PM
Social Hour with Lite Bites
Room: Divide/Ten Mile


Monday, June 12 | 7:30PM - 10:00PM
Poster Session 1
Room: Divide/Ten Mile


Tuesday, June 13 | 7:00AM - 8:00AM
Breakfast
Room: Bighorn/Champeaux


Tuesday, June 13 | 8:00AM - 11:00AM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? II

Room: Arapahoe

Speaker 1 of 5
* Tony L. Yaksh, University of California, San Diego, USA

Tuesday, June 13 | 8:00AM - 11:00AM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? II

Room: Arapahoe

Speaker 2 of 5
Patrick W. Mantyh, University of Arizona, USA
Mechanisms that Drive Cancer Pain

Tuesday, June 13 | 8:00AM - 11:00AM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? II

Room: Arapahoe

Speaker 3 of 5
Jerry F. Gebhart, University of Pittsburgh, USA
Preclinical Models: Visceral Pain States

Tuesday, June 13 | 8:00AM - 11:00AM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? II

Room: Arapahoe

Speaker 4 of 5
Nigel A. Calcutt, University of California, San Diego, USA
Painful Diabetic Neuropathy: Peripheral vs Central Mechanisms and Therapies

Tuesday, June 13 | 8:00AM - 11:00AM
Preclinical Behavioral Models: Models of Mechanisms and Pred
ictive Surrogates for the Human Experience? II

Room: Arapahoe

Speaker 5 of 5
Robert P. Yezierski, University of Florida, USA
The Injured Spinal Cord: At-Level Versus Below-Level Pain

Tuesday, June 13 | 9:20AM - 9:40AM
Coffee Break
Room: Gallery & Lakeside Suite


Tuesday, June 13 | 11:00AM - 1:00PM
Poster Setup
Room: Divide/Ten Mile


Tuesday, June 13 | 1:00PM - 10:00PM
Poster Viewing
Room: Divide/Ten Mile


Tuesday, June 13 | 2:30PM - 4:30PM
Workshop 2
Room: Arapahoe
1) Pharmacological Convergence between animal models…whither internal consistency. or are differences meaningful? 2) Model Potency; how good does the response have to be to be meaningful in humans, or does the preclinical profile mean anything in predicting human target? 3) When does the pain surrogate fail in predicting human analgesic efficacy? 4) Do side effects count in predicting efficacy?
Speaker 1 of 3
* Tony L. Yaksh, University of California, San Diego, USA

Tuesday, June 13 | 2:30PM - 4:30PM
Workshop 2
Room: Arapahoe
1) Pharmacological Convergence between animal models…whither internal consistency. or are differences meaningful? 2) Model Potency; how good does the response have to be to be meaningful in humans, or does the preclinical profile mean anything in predicting human target? 3) When does the pain surrogate fail in predicting human analgesic efficacy? 4) Do side effects count in predicting efficacy?
Speaker 2 of 3
Victor J. Hruby, University of Arizona, USA
Addressing the Mechanism of Prolonged and Neuropathic Pain with Novel Ligands that are Agonists at Opioid Receptors and Antagonists at NK-1 or CCK Receoptors

Tuesday, June 13 | 2:30PM - 4:30PM
Workshop 2
Room: Arapahoe
1) Pharmacological Convergence between animal models…whither internal consistency. or are differences meaningful? 2) Model Potency; how good does the response have to be to be meaningful in humans, or does the preclinical profile mean anything in predicting human target? 3) When does the pain surrogate fail in predicting human analgesic efficacy? 4) Do side effects count in predicting efficacy?

Short Talk(s) Chosen from Abstracts

Tuesday, June 13 | 4:30PM - 5:00PM
Coffee Available
Room: Gallery & Lakeside Suite


Tuesday, June 13 | 5:00PM - 7:00PM
Human Experimental Pain Model
Room: Arapahoe

Speaker 1 of 3
* Tony L. Yaksh, University of California, San Diego, USA

Tuesday, June 13 | 5:00PM - 7:00PM
Human Experimental Pain Model
Room: Arapahoe

Speaker 2 of 3
Lars Arendt-Nielsen, Aalborg University, Denmark
Experimental Models of Pain in Human

Tuesday, June 13 | 5:00PM - 7:00PM
Human Experimental Pain Model
Room: Arapahoe

Speaker 3 of 3
Irene Tracey, University of Oxford, UK
Developing Human FMRI and EEG as Surrogate Markers of Pain Processing and Pharmacological Analgesia

Tuesday, June 13 | 7:00PM - 8:00PM
Social Hour with Lite Bites
Room: Divide/Ten Mile


Tuesday, June 13 | 7:30PM - 10:00PM
Poster Session 2
Room: Divide/Ten Mile


Wednesday, June 14 | 7:00AM - 8:00AM
Breakfast
Room: Bighorn/Champeaux


Wednesday, June 14 | 8:00AM - 11:00AM
Organization of Clinical Analgesic Studies
Room: Arapahoe

Speaker 1 of 5
* Mitchell B. Max, University of Pittsburgh, Center for Pain Research, USA

Wednesday, June 14 | 8:00AM - 11:00AM
Organization of Clinical Analgesic Studies
Room: Arapahoe

Speaker 2 of 5
Paul J. Desjardins, Pfizer Consumer Healthcare, USA
Acute Postoperative Pain Models and Their Predictive Validity

Wednesday, June 14 | 8:00AM - 11:00AM
Organization of Clinical Analgesic Studies
Room: Arapahoe

Speaker 3 of 5
Jennifer A. Haythornthwaite, Johns Hopkins University, USA
Psychological Variables in Trial Design and Efficacy Assessment

Wednesday, June 14 | 8:00AM - 11:00AM
Organization of Clinical Analgesic Studies
Room: Arapahoe

Speaker 4 of 5
Dan Clauw, University of Michigan Medical School, USA
Studies of Complex Pain Syndromes: Fibromyalgia and Related Regional Pain Syndromes

Wednesday, June 14 | 8:00AM - 11:00AM
Organization of Clinical Analgesic Studies
Room: Arapahoe

Speaker 5 of 5
John T. Farrar, University of Pennsylvania School of Medicine, USA
The Design of Clinical Trials and Analgesic Drug Research

Wednesday, June 14 | 9:20AM - 9:40AM
Coffee Break
Room: Gallery & Lakeside Suite


Wednesday, June 14 | 2:30PM - 4:30PM
Workshop 3
Room: Arapahoe
1) Is there a value of experimental pain drug assessment in drug development, in achieving drug approval? 2) What end points matter?
Speaker 1 of 2
* Mitchell B. Max, University of Pittsburgh, Center for Pain Research, USA

Wednesday, June 14 | 2:30PM - 4:30PM
Workshop 3
Room: Arapahoe
1) Is there a value of experimental pain drug assessment in drug development, in achieving drug approval? 2) What end points matter?
Speaker 2 of 2
* Lars Arendt-Nielsen, Aalborg University, Denmark

Wednesday, June 14 | 4:30PM - 5:00PM
Coffee Available
Room: Gallery & Lakeside Suite


Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 1 of 6
Bob A. Rappaport, U.S. Food and Drug Administration, USA
A Common Sense Approach to Analgesic Drug Development and Approval

Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 2 of 6
Mitchell B. Max, University of Pittsburgh, Center for Pain Research, USA

Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 3 of 6
Dan Clauw, University of Michigan Medical School, USA

Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 4 of 6
John T. Farrar, University of Pennsylvania School of Medicine, USA

Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 5 of 6
Paul J. Desjardins, Pfizer Consumer Healthcare, USA

Wednesday, June 14 | 5:00PM - 7:00PM
Panel Discussion: Approval of Analgesic Drugs
Room: Arapahoe

Speaker 6 of 6
Lars Arendt-Nielsen, Aalborg University, Denmark

Wednesday, June 14 | 7:00PM - 8:00PM
Social Hour with Lite Bites
Room: Divide/Ten Mile


Thursday, June 15 | 2:30AM - 4:30AM
Workshop 4
Room: Arapahoe
1) What constitutes preclinical evidence for efficacy
2) Go/ No-go decision points


Thursday, June 15 | 7:00AM - 8:00AM
Breakfast
Room: Bighorn/Champeaux


Thursday, June 15 | 8:00AM - 11:00AM
Case Studies in Analgesic Development I
Room: Arapahoe

Speaker 1 of 3
Charles P. Taylor, Pfizer Global Research & Development, USA
Case Review of Gabapentin and Pregabalin

Thursday, June 15 | 8:00AM - 11:00AM
Case Studies in Analgesic Development I
Room: Arapahoe

Speaker 2 of 3
Ray G. Hill, Merck & Co., Inc., UK
The Development of Substance P (NK1 Receptor) Antagonists as Putative Analgesics

Thursday, June 15 | 8:00AM - 11:00AM
Case Studies in Analgesic Development I
Room: Arapahoe

Speaker 3 of 3
Stuart Apfel, Dov Pharmaceutical Inc., USA
Bicifadine, A Novel Reuptake Inhibitor, In the Treatment of Chronic and Acute Pain

Thursday, June 15 | 9:20AM - 9:40AM
Coffee Break
Room: Gallery & Lakeside Suite


Thursday, June 15 | 4:30PM - 5:00PM
Coffee Available
Room: Gallery & Lakeside Suite


Thursday, June 15 | 5:00PM - 7:00PM
Case Studies in Analgesic Drug development II
Room: Arapahoe

Speaker 1 of 2
Jonathan Moss, University Of Chicago, USA
Development of Methylnaltrexone: Pain Relief Without Side Effects

Thursday, June 15 | 5:00PM - 7:00PM
Case Studies in Analgesic Drug development II
Room: Arapahoe

Speaker 2 of 2
Smriti Iyengar, Eli Lilly and Company, USA
Case Review of Duloxetine

Thursday, June 15 | 7:00PM - 8:00PM
Social Hour with Lite Bites
Room: Divide/Gallery/Lakeside Suite


Thursday, June 15 | 8:00PM - 11:00PM
Entertainment
Room: Divide


Thursday, June 15 | 8:00PM - 11:00PM
Cash Bar
Room: Divide


Friday, June 16 | 10:26AM - 10:26AM
Departure


*Session Chair.