The anatomical distribution of Substance P (SP) has been investigated since
the development of antibodies against it in the 1970s. Although initial st
udies were performed with antibodies that also recognised the other endogen
ous neurokinins, most of the initial descriptions are surprisingly still va
lid today. in this review, we provide an integrated overview of the pathway
s containing SP in the central and peripheral nervous systems. The highest
densities of SP immunoreactivity occur in the superficial dorsal horn of th
e spinal cord, in the substantia nigra and in the medial amygdaloid nucleus
. In the peripheral nervous system, SP occurs in high concentrations in sma
ll diameter primary sensory fibres and in the enteric nervous system. SP is
extensively co-localised with classical transmitters and other neuropeptid
es. In the spinal cord, SP immunoreactive axonal boutons are preferentially
presynaptic to neurons expressing the SP receptor, suggesting that the neu
rokinin acts at a short distance from the release site. In contrast, in the
periphery, the situation probably differs in the autonomic ganglia, where
the targets are directly innervated by SP, and in other peripheral territor
ies, where SP has to diffuse through the connective tissue to reach the str
uctures expressing the receptor. (C) 2000 Harcourt Publishers Ltd.