An antagonist of substance P N-terminal fragments, D-substance P(1-7), reveals that both nociceptive and antinociceptive effects are induced by substance P N-terminal activity during noxious chemical stimulation

Virginia M. Goettl, Alice A. Larson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Substance P (SP) N-terminal fragments are known to alter nociception when injected intrathecally or when released in response to capsaicin. However, it is not known whether a sufficient concentration of SP N-terminal metabolites accumulate during noxious stimulation to modulate nociception. To test this, we examined the effect of the SP(1-7) antagonist, D-SP(1-7), injected intrathecally in mice, on two nociceptive assays that are differentially affected by exogenous SP(1-7): acetic acid-induced writhing that is inhibited and formalin-induced behaviors that are enhanced by SP(1- 7). One nmol of D-SP(1-7) is sufficient to block the acute (30 min) antinociceptive effects of SP(1-7) on writhing. When injected alone at much higher doses (10-100 nmol), D-SP(1-7) inhibited writhing. In the formalin assay, SP(1-7) had no acute effect (30 min) on responses during Phase 1 at any dose tested, but D-SP(1-7) increased responses 5 min after injection of low (2-1000 pmol), but not high doses (10 and 100 nmol). Twenty-four hours after injection of SP(1-7), writhing was inhibited and formalin responses were increased. D-SP(1-7) prevented these effects of SP(1-7) but had no effect when injected alone, indicating that there is no tonic SP N-terminal activity in mice not exposed to noxious stimuli. Thus, acetic acid and formalin each induce endogenous SP N-terminal activity, respectively, producing a pro-nociceptive effect that is relatively insensitive to D-SP(1- 7) and antinociception that is very sensitive to inhibition by D-SP(1-7).

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalBrain Research
Volume780
Issue number1
DOIs
StatePublished - Jan 5 1998

Bibliographical note

Funding Information:
The authors thank Kelley Kitto for his technical assistance and Dr. Susan Giovengo and Rubén Velázquez for their editorial assistance. This research is supported by U.S. Public Health Service Grant NIDA04090 to A.A.L. and ADAMHA Training Grant T32 DA07234-06 to V.M.G.

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

Keywords

  • Hyperalgesia
  • Intrathecal
  • Mouse
  • Pain
  • Substance P
  • Substance P fragment

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