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).
KeywordsPrimary Afferents Neurogenic Inflammation Central Synapse Sensory Transmitter Polymodal Nociceptors
Unable to display preview. Download preview PDF.
- 1.Von Euler US, Gaddum JH (1931) An unidentified depressor substance in certain tissue extracts. J Physiol 72: 74–87Google Scholar
- 2.Lembeck F (1950) Zur Frage der Übertragung afferenter Impulse. III. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks. Naunyn- Schmiedeberg’s Arch exp Path Pharmak 219: 197–213Google Scholar
- 4.Gamse R (1984) Physiologie und Pathophysiologic der Substanz P. Drug Res 34: 1–6Google Scholar
- 5.Nagy JJ (1982) Capsaicin: a chemical probe for sensory neuron mechanisms. In: Handbook of pharmacology, vol 15. Plenum Publishing Corp, pp 185–235Google Scholar
- 10.Saria A, Zhao Yan, Martling CR, Theodorsson-Norheim E, Petermann J, Fischer J A, Lundberg JM (1986) Tachykinins and CGRP in relation to reactions caused by C-fiber afferents. 30th IUPS Congress, Vancouver Abstract Proc, p 554Google Scholar
- 12.Matsuo T, Yanagisawa M, Otsuka M, Kanazawa I, Munekata E (1984) The excitatory action of the newly-discovered mammalian tachykinins, neurokinin and neurokinin p, on neurons of the isolated spinal cord of the newborn rat. Neurosci Res 2: 105–110Google Scholar
- 13.Wiesenfeld-Hallin Z, Hökfelt T, Lundberg JM, Forssmann WG, Reinecke M, Tschopp FA, Fischer JA (1984) Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Letters 52: 199–204CrossRefGoogle Scholar
- 14.Saria A, Gamse R, Lundberg JM, Hökfelt T, Theodorsson- Norheim E, Petermann J, Fischer JA (1985) Coexistence of tachykinins and calcitonin gene-related peptide in sensory nerves in relation to neurogenic inflammation. Tachykinin Antagonists, Fernstrom Foundation Series No 6, Elsevier, pp 149–157Google Scholar