The present project is designed to test the following hypotheses: That peripheral nerve transection leads to disruption of information from peripheral targets, which in turn leads to: 1. A signal to DRG cells to; a. upregulate growth proteins and cytoskeletal elements necessary for growth cone formation (priming) in both central and peripheral axons, b. withdraw the central fine primary afferent terminals from postsynaptic targets. 2. The combination of vacant synaptic sites and DRG cells primed for growth leads to central sprouting and neosynaptogenesis in lamina I and II. 3. Some of the resulting reconnections may be inappropriate and this could help explain the abnormal sensibility and pain that sometimes results from this lesion. Supporting preliminary evidence is that growth cones are found in laminae I and II within 2 weeks of sciatic nerve transection, that many axons but almost no synapses are labeled with GAP-43 in laminae I and II at this time and that direct staining of fine primary afferents is found over a much wider area on the operated side. If further evidence confirms the above hypotheses, the major significance will be that the remodeling of dorsal horn synaptic architecture is primarily an active process. That this process is not perfect is presumably a factor in the abnormal sensory states that sometimes follow peripheral nerve transection. The ultimate hope is that, if this active remodeling can be quantified and thus understood, it can be manipulated for the benefit of human suffering.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS010161-20
Application #
3394151
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1978-01-01
Project End
1999-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
20
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555