Differential effects on sensory nerve processes and behavioral alterations in the rat after treatment with antibodies...

Published work on the effects of antibodies to nerve growth factor (ANTI-NGF) treatment on rats has shown an increase in the number of unmyelinated central processes of dorsal root ganglia (DRG) neurons (31). This increase is interpreted to be sprouting of the central projections of the DRG neurons. To test for sprouting of the peripheral DRG projections, we quantitated the number of peripheral DRG processes in the peripheral nerves of ANTI-NGF-treated compared to untreated rats, following selective surgery to eliminate motor and sympathetic nerve fibers. We report the numbers of peripheral DRG processes in an NGF-deprived environment decrease by 48% compared to untreated controls and the decrease is selective for the unmyelinated fiber population. Since the majority of the unmyelinated population is nociceptive, two nociceptive behavioral measures, one reflexive (tail flick) and one nonreflexive (paw or skin pinch), were performed and demonstrated decreased responses in the ANTI-NGF-treated compared to untreated and preimmune-treated rats. These data suggest a directional effect, primarily on the unmyelinated sensory population which results in altered nociceptive behavior, induced by the suppression of one endogenous factor, NGF. Furthermore, it is important to note that the centrally directed sensory processes project to a central nervous system environment and the peripherally directed processes are in a peripheral nervous system environment. Thus, a single molecule may have different effects on directional growth of a neuronal population that may be related to the interactions available in the substrate of the environment.