Inhibition of the N-methyl-d-aspartate receptor unmasks the antinociception of endogenous opioids in the periphery

Guo Hua Zhang, Sun Seek Min, Geun Hee Seol, Kyu Sang Lee, Hongxiu Han, Yang In Kim, Hee Chul Han

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although N-methyl-d-aspartate (NMDA) receptor antagonists potentiate antinociceptive effects induced by various exogenous opioids at the spinal, supraspinal, or peripheral level, less is known regarding the interaction between NMDA and endogenous opioids in antinociception. We therefore assessed the effects of NMDA receptor antagonists on endogenous opioids in antinociception at the peripheral level by testing the ability of the locally administered receptor antagonists to modify pain-related behavior induced by carrageenan injection into the knee joint. The NMDA receptor antagonist AP-5 or the exogenous opioid morphine was injected intra-articularly before carrageenan injection and 5 h after carrageenan injection, respectively. We evaluated whether intra-articular injection of the opioid receptor antagonist naloxone reversed the analgesic effect of AP-5. In addition, we tested the effects of AP-5 on carrageenan-induced levels of the β-endorphin protein in dorsal root ganglia (DRG), saphenous nerve and synovial membrane. We found that AP-5 prevented and morphine reversed carrageenan-induced pain-related behavior. Intriguingly, injection of naloxone 5 h after carrageenan injection reversed the antinociceptive effects of AP-5 pre-treatment, although naloxone alone had no effect on carrageenan-induced pain-related behavior. Western blots showed that AP-5 pre-treatment followed by carrageenan injection resulted in a higher level of β-endorphin protein in the DRG and saphenous nerve, but not in the synovial membrane, than that observed following saline control treatment. These results suggest that inhibition of the NMDA receptor unmasks antinociception induced by endogenous opioids at the peripheral level, partly through the increased protein level of the endogenous μ-opioid peptide β-endorphin in DRG and saphenous nerve.

Original languageEnglish
Pages (from-to)233-237
Number of pages5
JournalPain
Volume143
Issue number3
DOIs
Publication statusPublished - 2009 Jun 1

Fingerprint

Carrageenan
Opioid Analgesics
Endorphins
Injections
Spinal Ganglia
Naloxone
Synovial Membrane
Pain
Morphine
Intra-Articular Injections
Proteins
Aptitude
Opioid Peptides
Narcotic Antagonists
Inhibition (Psychology)
aspartic acid receptor
Knee Joint
Aspartic Acid
Analgesics
Therapeutics

Keywords

  • Arthritic pain
  • Interaction
  • NMDA
  • Opioid
  • Periphery

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

Inhibition of the N-methyl-d-aspartate receptor unmasks the antinociception of endogenous opioids in the periphery. / Zhang, Guo Hua; Min, Sun Seek; Seol, Geun Hee; Lee, Kyu Sang; Han, Hongxiu; Kim, Yang In; Han, Hee Chul.

In: Pain, Vol. 143, No. 3, 01.06.2009, p. 233-237.

Research output: Contribution to journalArticle

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