This application is for a Mentored Research Scientist Development Award (K01). The broad long-term objective of the proposed studies is to examine the role of neuroimmune interactions in peripheral mechanisms of sensory neuron plasticity. Outlined are the specific aims of this project. 1) Determine if changes in the response properties of surviving sensory neurons, mediated by altered levels of proinflammatory cytokines in the affected nerve, underlie the recovery of nociceptive thresholds after ablation of IB4-binding neurons (Vulchanova et al, 2001). These studies will employ immunohistochemistry, teased-fiber recording of single unit activity, behavioral analysis of anti-sense treatment, and proteomics-based differential expression analysis. 2) Determine if upregulation of proinflammatory cytokines in the injured nerve after Spinal Nerve Ligation (SNL) is associated with changes in intact sensory neurons that may underlie mechanisms involved in the development of neuropathic pain.
This specific aim will be addressed using immuno-histochemistry, behavioral analysis of antisense treatment, and proteomics-based differential expression analysis. 3) Determine if inflammation-induced upregulation of cytokines in the intestinal wall is associated with altered response properties of visceral spinal sensory neurons. These studies will employ immunohistochemistry, teased-fiber recording of single-unit activity, and antisense treatment. These studies will elucidate the role of proinflammatory cytokines in states of sensory hypersensitivity and may lead to identifying new targets for chronic pain therapies. The project will allow the candidate to acquire expertise in proteomics and electrophysiology and will provide theoretical and experimental foundation for establishing independent research program in the underrepresented field of visceral pain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA017236-03
Application #
7074836
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Thomas, David A
Project Start
2004-06-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
3
Fiscal Year
2006
Total Cost
$122,933
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Schuster, D J; Dykstra, J A; Riedl, M S et al. (2013) Visualization of spinal afferent innervation in the mouse colon by AAV8-mediated GFP expression. Neurogastroenterol Motil 25:e89-100
Lyte, Mark; Vulchanova, Lucy; Brown, David R (2011) Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res 343:23-32
Vulchanova, Lucy; Schuster, Daniel J; Belur, Lalitha R et al. (2010) Differential adeno-associated virus mediated gene transfer to sensory neurons following intrathecal delivery by direct lumbar puncture. Mol Pain 6:31
Riedl, Maureen S; Braun, Patrick D; Kitto, Kelley F et al. (2009) Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing. J Neurosci 29:13377-88
Vulchanova, Lucy; Casey, Melissa A; Crabb, Gwen W et al. (2007) Anatomical evidence for enteric neuroimmune interactions in Peyer's patches. J Neuroimmunol 185:64-74