The overall goal of the present proposal is to further our understanding of the processing and modulation of sensory input at the spinal cord level in normal and neuropathic states. We focus our attention on the spinothalamic tract (STT) system, which is one of the major ascending nociceptive pathways. Neuronal elements which influence this system include intrinsic spinal cord systems. Dynorphin (DYN), gamma-amino butyric acid (GABA) and glycine (GLY) are important intrinsic systems which play a role in the processing and modulation of primary afferent input before it is relayed onto ascending tract cells. Nothing is known concerning the relationship of these intrinsic systems with STT cells nor how this relationship changes in abnormal or neuropathic conditions. Therefore, the specific goals of this proposal are to analyze at the light and electron microscopic levels, the relationship between primate STT cells and DYN, GABA and GLY terminals. The change in this relationship in the primate model of experimental peripheral neuropathy will then be analyzed. The long term goals of these studies are to gain an understanding of neural mechanisms involved in processing of sensory input, in the normal and neuropathic dorsal horn. Knowledge of the normal neurocircuitry is paramount to understanding and interpreting the neurocircuitry which arises in neuropathic states. Understanding the plasticity of neurocircuitry in peripheral neuropathy and its consequent physiological effects may lead to improved clinical treatment of this common neural disorder and elucidate neural mechanisms underlying hyperalgesia.
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