The research aims at elucidating the role of vanilloid receptors (VR) in the mediation of nociception in the dorsal horn of mammals. Immunocytochemistry of the VR1 receptor has shown that this is expressed mainly in small cells of dorsal root ganglia and in afferents to the superficial laminae of the dorsal horn. VR1-immunopositive terminals predominate in lamina I and are present in lamina II. In this lamina, however, most of the staining for VR1 is in dendrites postsynaptic to primary afferents. It was also established that VR1 terminals do not contain substance P (SP). Thus, two main classes of afferents may mediate nociception and the question arises whether they contact the same neurons. This will be established by studying, with confocal microscopy and electron microscopy, whether VR1- and SP-immunopositive terminals contact the same neuron expressing neurokinin receptors (NK1) in lamina I. It is predicted that, if VR1-positive afferents mediate nociception, these neurons will project to the parabrachial nucleus, a major destination for ascending nociceptive pathways in rodents. The research will also establish what glutamate receptor subunits are present at VR1-positive synapses in superficial laminae. In particular, the absence of NMDA receptor would signify a clearly different role for these synapses from that of afferents that release SP. Also this part of the research will require simultaneous multiple labeling at the light and electron microscopic level.
The third aim of the research is to test whether postsynaptic VR1 is related to activity in C fibers, independently from its origin, i.e. from intrinsic neurons or via transsynaptic traffic. The total depletion of VR1 in the dorsal horn after dorsal rhizotomy suggests an activity dependency of postsynaptic VR1 and this will be tested by conduction block of dorsal roots and, conversely, by selective activation of C fibers with cutaneous application of mustard oil.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS040885-01A1
Application #
6370603
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Kitt, Cheryl A
Project Start
2001-07-15
Project End
2005-06-30
Budget Start
2001-07-15
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$245,616
Indirect Cost
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
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
Fecho, K; Valtschanoff, J G (2006) Acute inflammatory and neuropathic pain in Lewis and Fischer rats. J Neuroendocrinol 18:504-13
Hwang, Se Jin; Oh, Jung Min; Valtschanoff, Juli G (2005) The majority of bladder sensory afferents to the rat lumbosacral spinal cord are both IB4- and CGRP-positive. Brain Res 1062:86-91
Hwang, Se Jin; Oh, Jung Min; Valtschanoff, Juli G (2005) Expression of the vanilloid receptor TRPV1 in rat dorsal root ganglion neurons supports different roles of the receptor in visceral and cutaneous afferents. Brain Res 1047:261-6
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
Bae, Yong Chul; Oh, Jung Min; Hwang, Se Jin et al. (2004) Expression of vanilloid receptor TRPV1 in the rat trigeminal sensory nuclei. J Comp Neurol 478:62-71
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
Hwang, Se Jin; Burette, Alain; Valtschanoff, Juli G (2003) VR1-positive primary afferents contact NK1-positive spinoparabrachial neurons. J Comp Neurol 460:255-65
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
Hwang, S J; Valtschanoff, J G (2003) Vanilloid receptor VR1-positive afferents are distributed differently at different levels of the rat lumbar spinal cord. Neurosci Lett 349:41-4

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