The research program is focused on mechanisms of excitotoxicity- induced chronic central pain (CCP) after SCI. The rodent contusion model of SCI will be used for assessing CCP and to explore the contributions of excitatory amino acid (EAA)-mediated mechanisms that lead to cell death after SCI. We hypothesize that damage caused by the elevated levels of EAA is causally related to the development of chronic pain as well as other dysfunctional states after SCI. The three projects will test molecular, biochemical and functional outcomes of interrupting EAA release of transport mechanisms and inhibiting EAA receptor- mediated processes, including apoptosis, in a combination of approaches. Project 1 will assess behavioral outcome and AA receptor and transporter distribution and density following blockage of EAA mediated processes and interventions of apoptotic pathways after SCI. Project 2 will measure EAA concentrations acutely after contusion injury and examine the role after EAA release, receptors and transporters play in neuronal loss after SCI. Project 3 will measure the expression levels of early genes (p50, p65, p49) activated by glutamate receptor-mediated mechanisms and the resulting downstream changes in expression of genes (Bcl-2 gene family) that influence neural cell survival after SCI. There are three cores: an administrative core, an animal core and a morphology core. The results for these studies will guide the development of strategic interventions to improve functional outcome after SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS039161-05
Application #
6838242
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Porter, Linda L
Project Start
2001-01-11
Project End
2007-12-31
Budget Start
2005-01-01
Budget End
2007-12-31
Support Year
5
Fiscal Year
2005
Total Cost
$1,176,593
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Hassler, Shayne N; Johnson, Kathia M; Hulsebosch, Claire E (2014) Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats. J Neurochem 131:413-7
Gwak, Young S; Hassler, Shayne E; Hulsebosch, Claire E (2013) Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats. Pain 154:1699-708
Crown, Eric D; Gwak, Young S; Ye, Zaiming et al. (2012) Calcium/calmodulin dependent kinase II contributes to persistent central neuropathic pain following spinal cord injury. Pain 153:710-21
Gwak, Young S; Kang, Jonghoon; Unabia, Geda C et al. (2012) Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol 234:362-72
Gwak, Young S; Hulsebosch, Claire E (2011) GABA and central neuropathic pain following spinal cord injury. Neuropharmacology 60:799-808
Gwak, Young Seob; Hulsebosch, Claire E (2011) Neuronal hyperexcitability: a substrate for central neuropathic pain after spinal cord injury. Curr Pain Headache Rep 15:215-22
Leem, Joong Woo; Kim, Hee Kee; Hulsebosch, Claire E et al. (2010) Ionotropic glutamate receptors contribute to maintained neuronal hyperexcitability following spinal cord injury in rats. Exp Neurol 224:321-4
Gwak, Young S; Unabia, Geda C; Hulsebosch, Claire E (2009) Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury. Exp Neurol 220:154-61
Gwak, Y S; Hulsebosch, C E (2009) Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. Neuroscience 161:895-903
Hulsebosch, Claire E; Hains, Bryan C; Crown, Eric D et al. (2009) Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev 60:202-13

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