Abstract

The proposed research plan is rooted in the notion that glutamate is a/the major neurotransmitter t the firs synapse established by peripheral nerve fibers in the central nervous system. Since peripheral nerve fibers with different functional characteristics release the same transmitter, postsynaptic mechanisms may be involved. These may include preferential termination of different types of afferent fibers onto different types of glutamate receptors. The first part of the proposed research will test this possibility. Peripheral nerve injury may result in hypergeusia, i.e. enhanced response to """"""""painful"""""""" stimuli, that may be blocked by glutamate antagonists. The neuronal hyperexcitability that may underlie hyperalgesia may be explained by changes in the density or distribution of glutamate receptors in dorsal horn neurons. This is what the second part of the proposed research plans to determine. The research planned here has not been possible until now at the microscopic level for lack of adequate methods. A modification of electron microscopic postembedding immunogold makes now possible to compare with accuracy qualtitive and quantitive aspects of glutamate receptors in injured and control spinal cord material.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012440-25
Application #
6393282
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Porter, Linda L
Project Start
1978-07-01
Project End
2003-06-30
Budget Start
2001-04-01
Budget End
2003-06-30
Support Year
25
Fiscal Year
2001
Total Cost
$212,603
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Willcockson, Helen; Valtschanoff, Juli (2008) AMPA and NMDA glutamate receptors are found in both peptidergic and non-peptidergic primary afferent neurons in the rat. Cell Tissue Res 334:17-23
Lucifora, Simona; Willcockson, Helen H; Lu, Chun-Rong et al. (2006) Presynaptic low- and high-affinity kainate receptors in nociceptive spinal afferents. Pain 120:97-105
Lu, Chun-Rong; Willcockson, Helen H; Phend, Kris D et al. (2005) Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. J Comp Neurol 486:169-78
Hwang, Se Jin; Burette, Alain; Rustioni, Aldo et al. (2004) Vanilloid receptor VR1-positive primary afferents are glutamatergic and contact spinal neurons that co-express neurokinin receptor NK1 and glutamate receptors. J Neurocytol 33:321-9
Boukhelifa, Malika; Hwang, Se Jin; Valtschanoff, Juli G et al. (2003) A critical role for palladin in astrocyte morphology and response to injury. Mol Cell Neurosci 23:661-8
Lu, Chun-Rong; Hwang, Se Jin; Phend, Kristen D et al. (2003) Primary afferent terminals that express presynaptic NR1 in rats are mainly from myelinated, mechanosensitive fibers. J Comp Neurol 460:191-202
Lu, Chun-Rong; Hwang, Se Jin; Phend, Kristen D et al. (2002) Primary afferent terminals in spinal cord express presynaptic AMPA receptors. J Neurosci 22:9522-9
Boukhelifa, M; Parast, M M; Valtschanoff, J G et al. (2001) A role for the cytoskeleton-associated protein palladin in neurite outgrowth. Mol Biol Cell 12:2721-9
Valtschanoff, J G; Rustioni, A; Guo, A et al. (2001) Vanilloid receptor VR1 is both presynaptic and postsynaptic in the superficial laminae of the rat dorsal horn. J Comp Neurol 436:225-35
Hwang, S J; Pagliardini, S; Rustioni, A et al. (2001) Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J Comp Neurol 436:275-89

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