? This project investigates the changes in opioid metabolism and response that are caused by sickle cell anemia (SCA). It has been observed that patients experiencing a sickle cell-related pain episode respond poorly to opioid therapy. Two murine models of SCA have been developed and will be tested to determine their utility in addressing this aspect of the disease. To determine if poor opioid response is caused by increased opioid clearance, the expression of opioid metabolizing enzymes in human and mouse liver with and without SCA will be measured with gene arrays and quantitative (real time) RT-PCR. To determine if the mouse models are appropriate for studying SCA related pain and analgesia, the baseline nociceptive thresholds of these animals will be compared with wild type mice using von Frey monofilaments, grip force reduction, and thermal sensory response. To determine if SCA mouse models display poor opioid analgesic efficacy and/or reduced potency similar to that observed in humans, a second battery of tests will be performed on SCA and wild type mice that have been dosed with an opioid analgesic. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA018484-01
Application #
6835278
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2004-08-30
Project End
2007-08-29
Budget Start
2004-08-30
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$31,347
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455