The broad objectives of this research are to understand sensory coding in the peripheral nervous system and to establish pharmacological treatments to disrupt these codes in different classes of afferents, and thereby achieve reversible, functionally selective sensory loss. The 3 specific aims are: 1. to determine the patterns of impulses in peripheral trunk axons, in dorsal root ganglion (DRG) cell bodies, and in dorsal roots (DR) induced by different physiological stimuli at various intensities. 2. to determine the ionic and metabolic mechanisms that shape these modality characteristic impulse patterns in the different regions of the peripheral afferents. 3. to exploit the knowledge gained in 1. and 2 by applying different drugs and/or electrical current at several loci along the nerve to disrupt patterns selectively in different functional classes of afferents. Neurological evaluations of motor, sensory and nociceptive capabilities will be made in behavioral tests of rats injected with drugs that have been shown to alter impulse patterns selectively in different fiber types in order to assess the differential block effects of those drugs. The results will determine i) how sensation can be abolished without total annihilation of peripheral nerve impulses, and ii) how the proper conditions of neuroactive drugs plus electrical current can accomplish this loss with functional selectivity and clinical utility. The scientific importance of this work is that it will provide definitive information about the relationship between impulse pharmacology and functional capabilities. The data will be the first to establish the relative susceptibility of sensor neurons according to their functional class instead of according to their physical characteristics (diameter, conduction velocity, locus). Such data are essential to interpret results of diagnostic differential blocking procedures in scientific studies of the neuronal circuitry underlying pain. The clinical relevance of these studies is that they present a foundation for the rational design and application of drugs in the peripheral nervous system to accomplish functionally selective nerve blocks. The work is intended to lead to new procedures for control of function, such as selective block of pain while preserving other sensations and motor function. Alternatively, selective blockade of motor axons could be used to reduce spasm and tremor without interference with sensation.
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