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Pharmacology

Substance P equals pain substance?

Nature volume 392, pages 334–335 (1998)Cite this article

Since von Euler and Gaddum first described substance P (SP) more than 60 years ago1, much evidence has accumulated to suggest that this undecapeptide is released from the terminals of certain sensory nerves, as a chemical neurotransmitter or modulator2. The sensory function of SP is thought, from more circumstantial evidence, to be related to the transmission of pain information into the central nervous system (CNS)2,3. This idea is now supported by two studies reported by Cao et al.4 and De Felipe et al.5 on pages 390 and 394, respectively, of this issue. Both groups find that when the function of SP is genetically disrupted in mice, the animals show reduced responses to painful stimuli.

Cao et al.4 studied mice in which the preprotachykinin A gene was disrupted. This gene encodes the precursor from which both SP and the closely related neuropeptide neurokinin A (NKA) are made. As expected, the mice lacked any detectable SP or NKA, although their development, ability to reproduce and behaviour were unaffected. The animals also showed normal thresholds for reactions to various painful stimuli, such as heat, mechanical pressure or chemical irritants. But when the intensity of the painful stimulus was increased, the knockout mice showed blunted responses, evidenced by increased latencies in the response to the stimulus. The importance of SP/NKA seemed to apply only to a certain ‘window’ of pain intensities — when the intensity of the pain stimulus was further increased, the responses of the knockout animals did not differ much from those of the wild-type mice.

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References

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  1. the Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK

    Leslie Iversen

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Iversen, L. Substance P equals pain substance?. Nature 392, 334–335 (1998). https://doi.org/10.1038/32776

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