Abstract
A heptadecapeptide (orphanin FQ or nociceptin) was recently identified as an endogenous ligand for the orphan opioid-like receptor. Here we report that intrathecal orphanin FQ produces dose-dependent depression of a spinal nociceptive flexor reflex in the rat. Furthermore, administration of orphanin FQ in rats with intrathecal catheters produced behavioural antinociception in the tail flick test with no signs of sedation or motor impairment. The reflex depressive effect of orphanin FQ was not reversed by antagonists of opioidergic, alpha 2-adrenergic and GABA-A receptors. Thus, orphanin FQ may suppress nociceptive input at the spinal level through an novel mechanism. Orphanin FQ or agonists of its receptor may represent novel analgesics for pain conditions which are not responsive to existing pharmacological therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-Antagonists / pharmacology
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Adrenergic beta-2 Receptor Antagonists
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Analysis of Variance
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Animals
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Bicuculline / pharmacology
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Electromyography
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Electroshock
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Female
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GABA-A Receptor Antagonists
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Imidazoles / pharmacology
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Injections, Spinal
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Muscle, Skeletal / innervation
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Naloxone / pharmacology
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Narcotic Antagonists
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Nerve Fibers / physiology
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Nociceptin
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Opioid Peptides / administration & dosage
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Opioid Peptides / pharmacology*
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Pain*
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid / agonists*
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Spinal Cord / drug effects
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Spinal Cord / physiology*
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Sural Nerve / physiology*
Substances
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Adrenergic alpha-Antagonists
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Adrenergic beta-2 Receptor Antagonists
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GABA-A Receptor Antagonists
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Imidazoles
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Narcotic Antagonists
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Opioid Peptides
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Receptors, Opioid
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atipamezole
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Naloxone
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Bicuculline