Requirement of nerve growth factor for development of substance P-containing sensory neurones.

Abstract

The protein nerve growth factor (NGF) is known to be essential for the maturation and maintenance of adrenergic neurones and for the development of sensory neurones during critical stages of embryonic life. The investigation of the physiological importance of NGF for the development of sensory neurones has been hampered so far by the lack of biochemical marker substances for these neurones. The demonstration that the undecapeptide substance P(SP) is present in sensory neurones suggests that it might be such a marker. SP is synthesized in dorsal root ganglia (DRG) and transported to the terminals of C-fibres located in the dorsal horn of the spinal cord and in the skin. Its release can be demonstrated from the central and peripheral endings of sensory nerve fibres which seem to have an important role in pain perception. We have investigated the effects of NGF and of purified anti-NGF antibodies on the content of SP in rat DRG and in their respective target organs, namely the spinal cord and the skin. The effects on sympathetic ganglia were included in order to control the effectiveness of both NGF and its antibody. We report here that NGF leads to an increase in SP in spinal ganglia, as previously shown by Kessler and Black. However, in contrast to these authors, we describe that the administration of anti-NGF antibodies produces a marked reduction of the SP content in sensory neurones and in their respective nerve terminals.