The long term objective of this research is to develop a model of spinal cord plasticity using nerve growth factor. This neuronotrophin appears to act selectively on nociceptive afferents that are responsible for signalling damage to the skin. The experiments will make use of electrophysiological, anatomical and behavioral methods to investigate various aspects of this plasticity in rats. Several hypotheses will be investigated, including a) the possibility that nociceptive afferents require NCF in a postnatal critical period and that deprivation from NGF results in conversion of these afferents to low threshold mechanoreceptors; b) that such conversion results in changes in spinal projection of these afferents; c) that behavioral hyperalgesia observed in NGF-treated adults results from changes in spinal projection systems, particularly those involving certain amino acid (NMDA) receptors; and d) that reinnervation of nociceptors in adults requires NCF. Experimental design involves examining the effects of NGF and its antibody on sensory neurons (identified physiologically or anatomically), on identified spinal neurons and circuits, and on certain behavioral responses to natural and electrical stimulation. Animals treated with NGF or anti-NGF will be compared to each other and to age-matched untreated controls. The health- related significance of these experiments derives from the need to have further basic information concerning the capacity of the adult nervous system to modify its connectivity after injury, and to document the ability of naturally-occurring biological agents such as NGF to regulate this plasticity. Furthermore, NGF is a candidate to promote regeneration of certain neuronal types after injury, and it is necessary to ascertain its functional effects on the mammalian spinal cord in vivo.
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