Grants and Contracts Details
Description
Spasticity, exaggerated stretch reflexes and abnormal muscle tone, poses a major detrimental impact on the
quality of life in a significant number of patients with spinal cord injury (SCI). Spasticity of the midline (axial)
musculature can significantly hinder performing transfers and lead to development of pressure sores. Currently, significant
gaps exist in our knowledge of the pathophysiology involved in spasticity development following SCI, especially regarding
the axial musculature. Recent observations in our laboratory, using a sacral spinal (S2)transection spasticity model, suggest
an increase in glutamatergic input to sacrocaudal (sacral (S) and coccygeal (Co" motoneurons arising ITompresumptive
spinal segmental sources. The goals of this proposal are: I) to determine the effects ofS, transection on the number and
distribution of glutarnatergic inputs, arising ITomprimary afferents or intraspinal sources, on more caudal motoneurons, 2)
to correlate these changes with the development of spasticity within the tail musculature, which are the caudal counterparts
to the trunk (axial) musculature, and 3) to examine the therapeutic efficacy of riluzole and gabapentin, which selectively
interfere with gIutamatergic transmission, in decreasing the development of spasticity within the tail musculature. Anirnals
with S2spinal transection will be tested behaviorally using our established system. At each of four well defined, progressive
stages of spasticity, temporal changes in gIutamatergic inputs to sacrocaudal motoneurons, arising ITomprimary afferents
or intraspinal sources, will be assessed using antibodies specific for these neuron subtypes and confocal microscopy.
Changes in number and distribution of immunoreactive connections to motoneuron soma and dendrites will be correlated
with changes in spasticity in the tail musculature. In a separate group of animals, a welh:stablished method of dorsal
rhizotomy, of the S,-C04 spinal roots, will determine the direct contribution of primary afferents to the total glutamate input
to sacrocaudal motoneurons in normal versus SCI-spastic animals. A final group of animals, demonstrating advanced
spasticity within the tail, will receive therapeutic doses of either riluzole or gabapentin and behaviorally tested. Results
ITomthese experiments will further define the role of the gIutamatergic system in the development of spasticity and assess
the efficacy of two clinically available drugs, which inhibit the glutamatergic system, in the management of SCI-induce
spasticity in the axial musculature.
Status | Finished |
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Effective start/end date | 1/15/05 → 1/14/09 |
Funding
- KY Spinal Cord and Head Injury Research Trust: $283,329.00
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