Opioid compounds modulate neurotransmission through a number of different sensory and motor systems. The long-term goals of the present proposal concern the modulation of sensory transmission, especially opioid modulation of nociceptive sensory systems at the spinal level. The immediate intent of this proposal is to concentrate on peripheral mechanisms by examining in detail the localization of delta, mu and kappa opioid receptors to different functional classes of primary afferent neurons. In addition, we will examine relationships between functional properties of afferent neurons and the expression of opioid receptors, vanilloid receptors, and binding sites for the lectin IB4. In making this proposal, immunohistochemical and electrophysiological approaches will be combined to address the following specific aims: Determine what functional classes of primary afferent neurons express opioid receptors. Determine what classes of thermal nociceptors express opioid and vanilloid receptors. Determine in functionally identified sensory neurons, the relationship between the expression of lectin binding sites and opioid and vanilloid receptors. Knowledge obtained from these experiments in the peripheral nervous system will contribute to our understanding of basic opioid mechanisms, and as such will further our understanding of central mechanisms related to the modulation of nociceptive and painful information in both the normal and pathologic states.
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