The presence of autoreceptors for simple neurotransmitters at synapses in t
he mammalian nervous system is well established. By contrast, the evidence
for such receptors modifying neuropeptide transmission is less obvious. Pro
bably the most well characterized of the neuropeptides is substance P (SP),
which appears to play a major role as a primary afferent modulator. This a
rticle highlights evidence to support the existence of auto receptors that
might modulate the release of this neuropeptide and which, therefore, could
be important in the design of drugs affecting SP function, not only in sen
sory processing, but also elsewhere in the brain.