The goal of these studies is to investigate the microcircuitry of the spinal cord dorsal horn to determine the relationship of various spinal cord structures to pain transmission systems. An understanding of spinal cord microcircuitry in the normal animal will allow us to determine if changes have occurred in hyperalgesic states, such as acute inflammation. The descending noradrenergic system is proposed as one route by which the perception of pain is modulated endogenously. Norepinephrine has been shown to selectively inhibit noxious input to spinothalamic tract neurons. We have recently shown in the past grant period that noradrenergic terminals synapse directly on the soma and proximal dendrites of lamina I, IV, and V neurons. This included three retrogradely identified and two intracellularly filled spinothalamic tract neurons. The intracellularly filled neurons were a wide dynamic range neuron and a high threshold neuron. The current proposal outlined here will continue study of the inhibitory noradrenergic system and expand the scope of the grant to study of glutamate and aspartate as examples of candidate excitatory neurotransmitters. Specifically, the dorsal horn will be surveyed to determine what arrangements exist within the normal dorsal horn with identified noradrenergic and then with excitatory amino acid structures. The relationship of noradrenergic and excitatory amino acid structures to spinothalamic tract neurons and their dendrites be examined in detail. It has been reported that glutamate content in primary afferent neurons. If possible, differences between glutamate structures from various sources will be identified. Finally, comparison of normal structure will be made with tissues at three time points after an experimentally induced inflammation of the knee capsule. Increased knowledge of the microcircuitry of inhibitory noradrenergic and excitatory amino acid systems in the normal and in the acute arthritis model may impact on our future effectiveness of pain management.
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