Abstract
Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain transmission. The aim of the present study was to investigate the role of the NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was performed in mice stressed by forced swimming in water at 15 degrees C (high severity swims) or 32 degrees C (low severity swims). High severity swims produced a naloxone-insensitive antinociceptive effect which was blocked by supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2 (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity swims produced a milder analgesic effect that was partially antagonized by naloxone, completely blocked by NC and potentiated by [Nphe1]NC(-13)NH2. These findings confirm the anti-analgesic role of supraspinal NC and suggest that endogenous NC signaling counteracts the opioid component of SIA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesia*
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Animals
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Central Nervous System / drug effects
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Central Nervous System / metabolism*
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Dose-Response Relationship, Drug
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Drug Interactions / physiology
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Male
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Mice
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Narcotic Antagonists
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Nociceptin
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Nociceptin Receptor
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Opioid Peptides / antagonists & inhibitors
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Opioid Peptides / metabolism*
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Opioid Peptides / pharmacology
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Pain / metabolism*
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Pain / physiopathology
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Pain Measurement
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Pain Threshold / drug effects
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Pain Threshold / physiology
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Peptide Fragments / pharmacology
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Reaction Time / drug effects
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Reaction Time / physiology
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Receptors, Opioid / metabolism*
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Signal Transduction / physiology*
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Stress, Physiological / metabolism*
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Stress, Physiological / physiopathology
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Swimming / physiology
Substances
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Narcotic Antagonists
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Opioid Peptides
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Peptide Fragments
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Receptors, Opioid
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nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-
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Nociceptin Receptor
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Oprl1 protein, mouse