Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia

Jennelle Durnett Richardson, Lin Aanonsen, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Cannabinoids, such as Δ9-THC, are capable of inhibiting nociception, i.e., pain transmission, at least in part, by interacting with spinal G(i)/G(o)-coupled cannabinoid receptors. What is not known, however, is the antinociceptive role of endogenous spinal cannabinoids. If endogenous cannabinoids modulate basal nociceptive thresholds, then alterations in this system could be involved in the etiology of certain pain states. In this report we provide evidence for tonic modulation of basal thermal nociceptive thresholds by the spinal cannabinoid system. Administration of oligonucleotides directed against CB1 cannabinoid receptor mRNA significantly reduced spinal cannabinoid binding sites and produced significant hyperalgesia when compared with a randomer oligonucleotide control. A second method used to reduce activity of the spinal cannabinoid receptor was intrathecal administration of the cannabinoid receptor antagonist SR 141716A. SR 141716A evoked thermal hyperalgesia with an ED50 of 0.0012 fmol. The SR 141716A-induced hyperalgesia was dose-dependently blocked by the administration of D-AP-5 or MK-801, two antagonists to the NMDA receptor. These results indicate that there is tonic activation of the spinal cannabinoid system under normal conditions. Furthermore, hypoactivity of the spinal cannabinoid system results in an NMDA-dependent hyperalgesia and thus may participate in the etiology of certain chronic pain states.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalJournal of Neuroscience
Volume18
Issue number1
DOIs
StatePublished - 1998

Keywords

  • Endogenous cannabinoid
  • Glutamate
  • Hyperalgesia
  • NMDA
  • Nociceptive threshold
  • SR 141716A
  • Spinal cord
  • Tonic

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia'. Together they form a unique fingerprint.

  • Cite this