This proposal is based upon the view that information derived from receptors located in the heart, lungs, and subdiaphragmatic regions, and transmitted via the vagal nerves to the CNS, interacts with excitatory and inhibitory CNS systems that modulate the processing of noxious input. The general objectives of the present proposal are to continue the analysis of this network by both extending behavioral analyses of vagal modulation of noxious somatosensory input and providing converging electrophysiological data supporting this view. This will be accomplished by (1) establishing the relative aversive-appetitive characteristics of cervical and subdiaphragmatic vagal stimulation in behavioral tests of escape and preference, (2) characterizing the effects of electrical stimulation in primary (nucleus tractus solitarius - NTS) and secondary (nucleus reticularis ventralis pars beta - NRV pars beta) sites of termination of vagal afferents in either facilitating or inhibiting the tail-flick reflex evoked by noxious heat, (3) establishing the spinal neurochemical basis of the nociceptive effects demonstrated in these escape, preference, and tail-flick experiments by intrathecal administration of receptor antagonists, (4) more fully characterizing midbrain and medullary substrates of the vagal network by assessing the effect of selective destruction of cell bodies with ibotenic acid on the capacity of electrical stimulation of the vagus to either facilitate or inhibit the tail-flick reflex, and (5) providing converging support for the role of the vagal network in the processing of noxious input by electrophysiological recordings of responses of class 2 and class 3 lumbar spinal dorsal horn neurons to either tibial nerve stimulation (A- and C-fiber intensities) or noxious heating of the foot during either electrical stimulation or microinjections of glutamate in the NTS and NRV regions.
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