Supraspinal administration of apelin-13 induces antinociception via the opioid receptor in mice

Peptides. 2009 Jun;30(6):1153-7. doi: 10.1016/j.peptides.2009.02.011. Epub 2009 Feb 24.


The effect of apelin-13 on pain modulation at the supraspinal level was investigated in mice using the tail immersion test. Intracerebroventricular (i.c.v.) administration of apelin-13 (0.3, 0.5, 0.8 and 3 microg/mouse) produced a dose- and time-related antinociceptive effect. This effect was significantly antagonized by the APJ receptor antagonist apelin-13(F13A), indicating an APJ receptor-mediated mechanism. Furthermore, naloxone, beta-funaltrexamine and naloxonazine, could reverse the analgesic effect. However, naltrindole or nor-binaltorphimine could not reverse the effect, suggesting that mu opioid receptor (primarily mu(1) opioid receptor subtype) is involved in the analgesic response evoked by apelin-13. Moreover, i.c.v. administration of apelin-13 potentiated the analgesic effect induced by morphine (i.c.v., 5 microg/kg) and this potentiated effect can be also reversed by naloxone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / pharmacology*
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Apelin Receptors
  • Injections, Intraventricular
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morphine / pharmacology
  • Narcotic Antagonists
  • Pain / drug therapy*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, Opioid / metabolism*
  • Time Factors


  • Analgesics, Opioid
  • Apelin Receptors
  • Aplnr protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Narcotic Antagonists
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid
  • apelin-13 peptide
  • Morphine