One of the fundamental rules regarding the organization of the spinal cord is that sensory information enters through the dorsal root, and the ventral roots carry motor commands. This important generalization has been challenged recently by the discovery of large numbers of afferent fibers in the ventral root. This number could represent more than 5% of the total sensory input to the spinal cord. However, the functional importance of these ventral root afferents is not yet clear. The long term goal of the present proposal is to determine the anatomical organization and the physiological role of the mammalian ventral root afferent system. A peculiar anatomical feature of ventral root afferent fibers is the suggestion from our recent preliminary data that many of these fibers are third branches of the dorsal root ganglion cells, in addition, to their processes in the dorsal root and in the periphery. Available literature, together with our findings during the last grant period, suggest that ventral root afferent fibers play important roles in pain transmission, including deep somatic and visceral pain. Therefore, the following hypotheses are formulated: 1) many ventral root afferent fibers are third branches of the dorsal root ganglion cells and this organization bears important functional consequences; and 2) ventral root afferent fibers play an important role in pain. The present application proposes a series of experiments that are designed to test the above hypotheses. In the first part of the application, electrophysiological recording of the action potentials from the ventral root afferent fibers in proposed to characterize ventral root afferent fibers. Experiments using injection of neuroanatomical markers into the dorsal root ganglion cells are then proposed to visualize their processes, including the one in the ventral root. In the second part of the application, the role of ventral root afferent fibers in pain transmission will be examined by investigating ventral root afferent inputs to monkey spinothalamic tract cells, the best studied pain tract cells. Accomplishing the specific aims will help to unveil important information on the anatomical organization and function of the ventral root afferent system. This would be important not only for our basic understanding of the sensory system, but also for its potential clinical applicability.
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