Our long-term objectives is to elucidate the central mechanisms and neuroblastic underlying acute and chronic pain. While alterations in C- fiber function have been implicated in several chronic pain conditions, the role of C-fiber afferent in the normal development of neuronal properties in central somatosensory pathways, let alone in the development of disordered pain behavior, is still unclear. C-fibers do provide nociceptive afferent excitatory inputs to V brainstem and spinal and spinal neurons, but recent studies have drawn attention to the possible neuroeffector and neurotrophic influences that C fibers may also exert; these neuroblastic influence including shaping neuronal receptive field and response properties in both nociceptive and non-nociceptive pathways. Do C-fibers have a similar role in the normal development of these properties i the V somatosensory system? We will address this question, by testing: Hypothesis I, that the neonatal depletion of C- fiber afferent produces alterations in the receptive field and response properties of nociceptive neurons in subnucleus caudalis of the adult V brainstem complex; Hypothesis II, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the subnucleus caudalis of the adult V brainstem complex; and Hypothesis III, that the neonatal depletion of C-fiber afferent produces alterations in the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. Since C-fiber primary afferent do not project to the V main sensory nucleus changes associated with neonatal capsaicin administration is an alteration to the modulatory influence that caudalis exerts on main sensory neurons; we will therefore also test: Hypothesis IV, that the neonatal depletion of C-fiber afferent produces alteration in the modulatory influences of subnucleus caudalis on the receptive field and response properties of low-threshold mechanoreceptive (LTM) neurons in the main sensory nucleus of the adult V brainstem complex. For each series of experiments, neonatal rats will be injected with capsaicin to deplete their C-fiber afferent and then at 2-3 months of age we will characterize, and compare with control animals, the properties of neurons in V subnucleus caudalis, which acts as the as the primary brainstem relay of nociceptive information, or in the main sensory nucleus which acts as the principal LTM brainstem relay in the vibrissa pathway to cortex. In both groups of animals, main sensory neuronal properties will also be tested during manipulation of the ascending caudalis modulatory influences by local anesthetic or glutamate injections of caudalis. The significance of these studies lies in their integral link to neuroblastic processes operating in the V brainstem complex and the determinants of receptive field and response properties of V somatosensory neurons, and to the view that altered C-fiber function may be involved in the development of several chronic pain conditions.
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