Enhanced nociception by exogenous and endogenous substance P given into the spinal cord in mice lacking NR2A/ε1, an NMDA receptor subunit

Makoto Inoue, Masayoshi Mishina, Hiroshi Ueda

Research output: Contribution to journalArticlepeer-review

Abstract

In capsaicin-pretreated mice, the nociceptive responses induced by intrathecally (i.t.) administered substance P (SP) were enhanced by N-methyl-D-aspartate (NMDA)-type receptor antagonists, dizocilpine (MK801) and D-2-amino-5-phosphonopentanoate (D-AP5) in a dose-dependent manner. Similar enhancement of SP-induced nociception was also observed in mice lacking the NMDA-type glutamate receptor NR2A/ε1 subunit gene (GluRε1(-/-) mice). On the other hand, GluRε1(-/-) mice showed a marked enhancement of the peripheral nociceptive responses induced by intraplantar (i.pl.) injection of SP and bradykinin (BK). As the nociceptive responses to SP and BK (i.pl.) were both antagonized by CP-99994, an neurokinin1 (NK1) antagonist (i.t.), these results suggest that GluRε1 receptor may play an inhibitory role in the downstream mechanisms of primary nociceptive SP neurones, possibly through activation of unidentified inhibitory neurones.

Original languageEnglish (US)
Pages (from-to)239-241
Number of pages3
JournalBritish Journal of Pharmacology
Volume129
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • NMDA
  • Spinal cord
  • Substance P
  • Supersensitization

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Enhanced nociception by exogenous and endogenous substance P given into the spinal cord in mice lacking NR<sub>2</sub>A/ε<sub>1</sub>, an NMDA receptor subunit'. Together they form a unique fingerprint.

Cite this