NOCICEPTORS AND GLUTAMATE RECEPTORS

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DESCRIPTION (adapted from applicant's abstract): Cutaneous nociceptors are a heterogeneous group of peripheral sensory neurons that sense noxious, damage-causing stimuli in the periphery and transmit that signal to the central nervous system. They extend their processes peripherally and centrally from cell bodies located in the dorsal root ganglia (DRG). The primary site of termination of the central projection of these unmyelinated and lightly myelinated fibers is predominantly in the superficial laminae (I and II) of the spinal cord dorsal horn. There are multiple subpopulations of nociceptors with cells bodies in the dorsal root ganglion (DRG). They can be grouped by sensory modality, by intracellular markers such as peptides, or by surface markers such as those developed and characterized by Dodd and Jessell (1985). We will use immunocytochemistry to identify DRG nociceptor subpopulations. We will test individual populations of nociceptors for expression of several nociceptive properties including low and high threshold heat and capsaicin sensitivity, using Ca2+ imaging and electrophysiology to measure responses. Kainate and AMPA receptors are expressed on subpopulations of DRG neurons, including functionally identified nociceptors, although the subpopulations of nociceptors have not yet been identified. Kainate and AMPA receptors expressed by nociceptors have been suggested to contribute to detection of damaging stimuli in the skin (Carlton and Coggeshall, 1995; Jackson and Hargreaves, 1995). There is immunocytochemical evidence for peripheral kainate and AMPA receptor expression (Coggeshall and Carlton, 1998) that could underlie such a transduction mechanism. There is physiological evidence that DRG neurites central to the ganglion itself respond to kainate, suggesting kainate or AMPA receptors may have a function at the central terminals of nociceptors, as well (Agrawal and Evans, 1986). Using the spinal cord slice preparation with attached dorsal root and co-cultures of identified nociceptors and dorsal horn neurons, we will investigate where AMPA and kainate receptors are expressed central to the DRG and specifically whether they are expressed on the nociceptor nerve terminals. We will determine the impact of receptor activation on glutamate release from the primary afferent terminals.