Spinal analgesic activity of orphanin FQ/nociceptin and its fragments

Neurosci Lett. 1997 Feb 21;223(2):113-6. doi: 10.1016/s0304-3940(97)13414-0.

Abstract

Previous work reveals that orphanin FQ/nociceptin (OFQ/N) administered supraspinally produces an initial hyperalgesic response followed by analgesia. Spinally, OFQ/N elicits a rapidly appearing, naltrexone-reversible, dose-dependent analgesia in the tailflick assay without any indication of hyperalgesia. Two OFQ/N fragments, OFQ/N (1-7) and OFQ/N (1-11), are active, but far weaker. Blockade of sigma receptors with haloperidol enhances the analgesic potency of spinal OFQ/N, OFQ/N (1-7) and OFQ/N (1-11), but not as dramatically as supraspinal OFQ. Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/N receptor (KOR-3) partially block OFQ/N analgesia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Antisense Elements (Genetics) / pharmacology
  • Cloning, Molecular
  • Drug Synergism
  • Exons
  • Haloperidol / pharmacology
  • Hyperalgesia / chemically induced
  • Male
  • Mice
  • Mice, Inbred Strains
  • Opioid Peptides / pharmacology*
  • Peptide Fragments / pharmacology*
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / genetics
  • Receptors, sigma / antagonists & inhibitors
  • Spinal Cord / drug effects*

Substances

  • Analgesics
  • Antisense Elements (Genetics)
  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • Receptors, sigma
  • nociceptin
  • nociceptin receptor
  • Haloperidol