Modulation of N-methyl-D-aspartate and (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a N-terminal fragment of substance P

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Abstract

The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1-7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate (NMDA) and (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were tested by combined single-unit extracellular recordings/microiontophoresis. While SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn nociceptive neurons. NMDA responses were transiently decreased (by an average of 36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by 76% at maximum). In contrast, AMPA responses were only increased by SP-(1-7) (by 81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel mechanism by which SP and EAAs interact to modulate pain transmission.

Original languageEnglish (US)
Pages (from-to)441-444
Number of pages4
JournalEuropean Journal of Pharmacology
Volume216
Issue number3
DOIs
StatePublished - Jun 17 1992

Bibliographical note

Funding Information:
This work was supported by NIDA Grants RO1-04090 and RO1-00124 to A.A.L. and RO1-04274, RO1-01933 and KO2-000145 to G.L.W. We thank Kelley Kitto for his expert technical assistance.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • (Extracellular recording)
  • AMPA
  • Iontophoresis
  • NMDA (N-methyl-D-aspartate)
  • Nociception
  • Spinal cord
  • Substance P-(1-7)

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