It is estimated that more than 100 million people suffer from chronic pain and more than 30 million people suffer from chronic itch in the U.S. Current therapeutics for chronic pain and itch are inadequate and limited by insufficient efficacy and side effects. Although itch-sensing neurons are a subset of C-fiber nociceptors in dorsal root ganglion, pain and itch are mediated via distinct neural circuits in the spinal cord. There is also crosstalk between pain and itch pathways: pain suppresses itch while analgesic such as morphine can provoke itch. Therefore it will be of great importance to develop new drugs that can target both pain and itch. Toward this goal, we have come up with a novel strategy of developing monoclonal antibodies to treat pain and itch simultaneously. We will employ a multidisciplinary approach that combines molecular biology, biochemistry, electrophysiology in isolated cells, whole DRG preparation, and spinal cord slices, and behavioral testing of pain and itch using evoked and spontaneous responses. Successful accomplishment of the project will not only provide a better understanding of the molecular and synaptic mechanisms of pain and itch sensations but also lead to new therapies for treating debilitating pain and itch conditions.

Public Health Relevance

Current treatments for debilitating chronic pain and itch conditions are limited by efficacy and side effects. We propose to develop novel monoclonal antibodies for pain and itch relief and further test the effects of these antibodies on behaviors and spinal cord synaptic transmission in mouse models of acute and chronic pain and itch. Our proposal will lead to novel therapeutics to treat pain and itch-related disease conditions and also provide new insights into synaptic mechanisms of pain and itch.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS089479-01
Application #
8795390
Study Section
Special Emphasis Panel (ZNS1-SRB-N (06))
Program Officer
Oshinsky, Michael L
Project Start
2014-09-30
Project End
2018-07-31
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$314,334
Indirect Cost
$114,334
Name
Duke University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705