The Role of Substance P and Other Neuropeptides in Transmission of Pain

For decades only few endogenous low molecular weight substances were considered as neurotransmitters, fulfilling the generally accepted criteria (Table 1). Among these substances are acetylcholine, monoamines and amino-acids. Recently, a large number of peptides has been described being localized in a variety of different neurons of the central and peripheral nervous system. Among the several dozens of known neuropeptides, the undecapeptide substance P (SP) is better characterized than most others. This does not mean that it is the most important one but reflects the early discovery by von Euler and Gaddum1. This was at a time when Sir Henry Dale speculated that the discovery of the mediator of antidromic vasodilation, which was assumed as the peripheral function of an afferent nociceptive neuron, should lead to the discovery of the neurotransmitter at the central synapse. Following this idea, Lembeck2 proposed SP as sensory transmitter because it was found in high concentrations in the dorsal horn of the spinal cord, i.e., the region where primary afferents terminate and because it caused peripheral vasodilation. However, only after the determination of the amino-acid sequence (Table 1) of SP in 19713, the required criteria for SP being a neurotransmitter were established (Table 1).