Functional antagonism of μ-, δ- and κ-opioid antinociception by orphanin FQ

Jeffrey S. Mogil, Judith E. Grisel, Ge Zhangs, John K. Belknap, David K. Grandy

Research output: Contribution to journalArticlepeer-review

214 Scopus citations


Orphanin FQ (OFQ) is the recently isolated endogenous ligand for the orphan opioid-like receptor, LC132. Initial reports suggested that OFQ increased pain sensitivity when injected intracerebroventricularly (i.c.v.) in mice. However, we have recently demonstrated that OFQ is instead an anti-opioid peptide that reverses morphine- and opioid-mediated stress-induced antinociception. Morphine binds to multiple opioid receptor types (μ, δ, and κ). The present study was designed to examine specific interactions of OFQ with antinociception mediated by each receptor type. To this end, mice were administered i.c.v. cocktails containing either vehicle or OFQ (10 nmol) and a μ-specific ([D-Ala2,N-Me-Phe4-Gly-ol]enkephalin; DAMGO; 0-0.1 nmol), δ-specific ([D-Pen2, D-Pen5]enkephalin; DPDPE; 0-50 nmol), or κ-specific (U-50,488H; 0-1000 nmol) agonist. As we have shown previously, OFQ alone had no effect on nociceptive sensitivity. OFQ was, however, able to completely block supraspinal antinociception produced by all three receptor type-selective agonists. We conclude, therefore, that OFQ functionally antagonizes μ (and (opioid receptors, and may play a general role in opioid modulation.

Original languageEnglish (US)
Pages (from-to)131-134
Number of pages4
JournalNeuroscience Letters
Issue number2-3
StatePublished - Aug 23 1996
Externally publishedYes


  • Anti-opiate
  • Delta
  • Kappa
  • LC132 receptor
  • Mu
  • Orphanin FQ
  • Pain inhibition

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Functional antagonism of μ-, δ- and κ-opioid antinociception by orphanin FQ'. Together they form a unique fingerprint.

Cite this