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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / pharmacology*
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Animals
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Antisense Elements (Genetics) / pharmacology
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Cloning, Molecular
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Drug Synergism
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Exons
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Haloperidol / pharmacology
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Hyperalgesia / chemically induced
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Male
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Mice
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Mice, Inbred Strains
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Nociceptin
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Nociceptin Receptor
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Opioid Peptides / pharmacology*
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Peptide Fragments / pharmacology*
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Receptors, Opioid / agonists*
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Receptors, Opioid / drug effects
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Receptors, Opioid / genetics
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Receptors, sigma / antagonists & inhibitors
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Spinal Cord / drug effects*
Substances
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Analgesics
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Antisense Elements (Genetics)
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Opioid Peptides
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Peptide Fragments
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Receptors, Opioid
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Receptors, sigma
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Haloperidol
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Nociceptin Receptor
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Oprl1 protein, mouse