Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide

Judith E. Grisel, Jeffrey S. Mogil, John Belknap, David Grandy

    Research output: Contribution to journalArticle

    128 Citations (Scopus)

    Abstract

    Orphanin FQ (OFQ), the endogenous ligand for the orphan opioid receptor, LC132, was recently isolated and characterized. The anti-opioid role of OFQ in supraspinal pain modulation was demonstrated by our previous observations that intracerebroventricular (i.c.v.) OFQ administration dose-dependently reverses systemic morphine antinociception and opioid-mediated stress-induced antinociception. The present study was designed to evaluate whether OFQ also modulates the antinociceptive actions of morphine in the spinal cord. Immediately after assessment of baseline nociceptive sensitivity on the 49°C tail-withdrawal assay, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktails of morphine (0, 1, 10 or 50 μg [0-135 nmol]) and OFQ (0 or 10 nmol), and re-tested 15, 30 and 60 min later. OFQ alone did not affect nociceptive sensitivity when administered by either route. Following i.c.v. administration, the antinociception produced by 10 μg morphine was completely reversed by 10 nmol OFQ; antinociception induced by 50 μg morphine was significantly antagonized. In contrast, OFQ was completely ineffective against antinociception induced by i.t. morphine. These findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites.

    Original languageEnglish (US)
    Pages (from-to)2125-2129
    Number of pages5
    JournalNeuroReport
    Volume7
    Issue number13
    StatePublished - 1996

    Fingerprint

    Opioid Peptides
    Morphine
    Opioid Analgesics
    nociceptin
    Opioid Receptors
    Tail
    Spinal Cord
    Central Nervous System
    Ligands
    Pain

    Keywords

    • LC132 receptor
    • Morphine
    • Nociception
    • Pain inhibition

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Grisel, J. E., Mogil, J. S., Belknap, J., & Grandy, D. (1996). Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. NeuroReport, 7(13), 2125-2129.

    Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. / Grisel, Judith E.; Mogil, Jeffrey S.; Belknap, John; Grandy, David.

    In: NeuroReport, Vol. 7, No. 13, 1996, p. 2125-2129.

    Research output: Contribution to journalArticle

    Grisel, JE, Mogil, JS, Belknap, J & Grandy, D 1996, 'Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide', NeuroReport, vol. 7, no. 13, pp. 2125-2129.
    Grisel JE, Mogil JS, Belknap J, Grandy D. Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. NeuroReport. 1996;7(13):2125-2129.
    Grisel, Judith E. ; Mogil, Jeffrey S. ; Belknap, John ; Grandy, David. / Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide. In: NeuroReport. 1996 ; Vol. 7, No. 13. pp. 2125-2129.
    @article{dd0a1ced39a94275935256a217c99e87,
    title = "Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide",
    abstract = "Orphanin FQ (OFQ), the endogenous ligand for the orphan opioid receptor, LC132, was recently isolated and characterized. The anti-opioid role of OFQ in supraspinal pain modulation was demonstrated by our previous observations that intracerebroventricular (i.c.v.) OFQ administration dose-dependently reverses systemic morphine antinociception and opioid-mediated stress-induced antinociception. The present study was designed to evaluate whether OFQ also modulates the antinociceptive actions of morphine in the spinal cord. Immediately after assessment of baseline nociceptive sensitivity on the 49°C tail-withdrawal assay, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktails of morphine (0, 1, 10 or 50 μg [0-135 nmol]) and OFQ (0 or 10 nmol), and re-tested 15, 30 and 60 min later. OFQ alone did not affect nociceptive sensitivity when administered by either route. Following i.c.v. administration, the antinociception produced by 10 μg morphine was completely reversed by 10 nmol OFQ; antinociception induced by 50 μg morphine was significantly antagonized. In contrast, OFQ was completely ineffective against antinociception induced by i.t. morphine. These findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites.",
    keywords = "LC132 receptor, Morphine, Nociception, Pain inhibition",
    author = "Grisel, {Judith E.} and Mogil, {Jeffrey S.} and John Belknap and David Grandy",
    year = "1996",
    language = "English (US)",
    volume = "7",
    pages = "2125--2129",
    journal = "NeuroReport",
    issn = "0959-4965",
    publisher = "Lippincott Williams and Wilkins",
    number = "13",

    }

    TY - JOUR

    T1 - Orphanin FQ acts as a supraspinal, but not a spinal, anti-opioid peptide

    AU - Grisel, Judith E.

    AU - Mogil, Jeffrey S.

    AU - Belknap, John

    AU - Grandy, David

    PY - 1996

    Y1 - 1996

    N2 - Orphanin FQ (OFQ), the endogenous ligand for the orphan opioid receptor, LC132, was recently isolated and characterized. The anti-opioid role of OFQ in supraspinal pain modulation was demonstrated by our previous observations that intracerebroventricular (i.c.v.) OFQ administration dose-dependently reverses systemic morphine antinociception and opioid-mediated stress-induced antinociception. The present study was designed to evaluate whether OFQ also modulates the antinociceptive actions of morphine in the spinal cord. Immediately after assessment of baseline nociceptive sensitivity on the 49°C tail-withdrawal assay, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktails of morphine (0, 1, 10 or 50 μg [0-135 nmol]) and OFQ (0 or 10 nmol), and re-tested 15, 30 and 60 min later. OFQ alone did not affect nociceptive sensitivity when administered by either route. Following i.c.v. administration, the antinociception produced by 10 μg morphine was completely reversed by 10 nmol OFQ; antinociception induced by 50 μg morphine was significantly antagonized. In contrast, OFQ was completely ineffective against antinociception induced by i.t. morphine. These findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites.

    AB - Orphanin FQ (OFQ), the endogenous ligand for the orphan opioid receptor, LC132, was recently isolated and characterized. The anti-opioid role of OFQ in supraspinal pain modulation was demonstrated by our previous observations that intracerebroventricular (i.c.v.) OFQ administration dose-dependently reverses systemic morphine antinociception and opioid-mediated stress-induced antinociception. The present study was designed to evaluate whether OFQ also modulates the antinociceptive actions of morphine in the spinal cord. Immediately after assessment of baseline nociceptive sensitivity on the 49°C tail-withdrawal assay, mice of both sexes were given i.c.v. or intrathecal (i.t.) cocktails of morphine (0, 1, 10 or 50 μg [0-135 nmol]) and OFQ (0 or 10 nmol), and re-tested 15, 30 and 60 min later. OFQ alone did not affect nociceptive sensitivity when administered by either route. Following i.c.v. administration, the antinociception produced by 10 μg morphine was completely reversed by 10 nmol OFQ; antinociception induced by 50 μg morphine was significantly antagonized. In contrast, OFQ was completely ineffective against antinociception induced by i.t. morphine. These findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites.

    KW - LC132 receptor

    KW - Morphine

    KW - Nociception

    KW - Pain inhibition

    UR - http://www.scopus.com/inward/record.url?scp=0029804988&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0029804988&partnerID=8YFLogxK

    M3 - Article

    VL - 7

    SP - 2125

    EP - 2129

    JO - NeuroReport

    JF - NeuroReport

    SN - 0959-4965

    IS - 13

    ER -