Nociceptin/orphanin FQ: Pain, stress and neural circuits

Research output: Contribution to journalShort survey

30 Scopus citations


First isolated some 10 years ago as the endogenous ligand for the "orphan opioid receptor" (ORL-1, now designated NOP), nociceptin/orphanin FQ (N/OFQ) has proved to be a potent inhibitory neuropeptide found across the neuraxis. Because of the homologies between opioids and N/OFQ, functional studies of this peptide have focused most heavily on pain and analgesia. This behavioral literature has been marked by a lack of consistency across laboratories, but much of the data can be explained by considering the potent inhibitory actions of N/OFQ in well-defined modulatory circuits. Presently, the most closely studied such circuit is the rostral ventromedial medulla (RVM), where administration of N/OFQ can block opioid analgesia (by inhibiting opioid-activated pain-inhibiting neurons), but under other conditions produces apparent hypoalgesia (by inhibiting pain-facilitating neurons). The net behavioral effect of N/OFQ in the RVM thus depends on whether experimental conditions are such that the pain-facilitating or pain-inhibiting neurons are active at the time the peptide is given. An important recent finding is that N/OFQ antagonists have antinociceptive properties when given supraspinally. Although the likelihood of interactions between stress and analgesia systems must be considered in interpreting these data, they suggest that N/OFQ antagonists have potential as clinically useful analgesic drugs.

Original languageEnglish (US)
Pages (from-to)3127-3132
Number of pages6
JournalLife Sciences
Issue number25
StatePublished - Nov 4 2005


  • Circuit-analysis
  • Orphanin FQ
  • Pain
  • Stress

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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