Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain

Tatsuo Yamamoto, Alan Kozikowski, Jia Zhou, Joseph H. Neale

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: The peptide neurotransmitter N-Acetylaspartylglutamate (NAAG) is the third most prevalent transmitter in the mammalian central nervous system. Local, intrathecal and systemic administration of inhibitors of enzymes that inactivate NAAG decrease responses to inflammatory pain in rat models. Consistent with NAAG's activation of group II metabotropic glutamate receptors, this analgesia is blocked by a group II antagonist. Results: This research aimed at determining if analgesia obtained following systemic administration of NAAG peptidase inhibitors is due to NAAG activation of group II mGluRs in brain circuits that mediate perception of inflammatory pain. NAAG and NAAG peptidase inhibitors, ZJ43 and 2-PMPA, were microinjected into a lateral ventricle prior to injection of formalin in the rat footpad. Each treatment reduced the early and late phases of the formalin-induced inflammatory pain response in a dose-dependent manner. The group II mGluR antagonist reversed these analgesic effects consistent with the conclusion that analgesia was mediated by increasing NAAG levels and the peptide's activation of group II receptors. Conclusion: These data contribute to proof of the concept that NAAG peptidase inhibition is a novel therapeutic approach to inflammatory pain and that these inhibitors achieve analgesia by elevating synaptic levels of NAAG within pain processing circuits in brain.

Original languageEnglish
Article number31
JournalMolecular Pain
Volume4
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

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Glutamate Carboxypeptidase II
Protease Inhibitors
Analgesics
Pain
Analgesia
Formaldehyde
Peptides
Pain Perception
Metabotropic Glutamate Receptors
Lateral Ventricles
Brain
Enzyme Inhibitors
Neurotransmitter Agents
N-acetyl-1-aspartylglutamic acid
Central Nervous System
Injections
Therapeutics

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain. / Yamamoto, Tatsuo; Kozikowski, Alan; Zhou, Jia; Neale, Joseph H.

In: Molecular Pain, Vol. 4, 31, 01.08.2008.

Research output: Contribution to journalArticle

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