Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice

Oleg Kambur, Pekka T Männistö, Kaarin Viljakka, Ilkka Reenilä, Kim Lemberg, Vesa K Kontinen, Maria Karayiorgou, Joseph Gogos, Eija Kalso

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.
    Alkuperäiskielienglanti
    LehtiBasic & Clinical Pharmacology & Toxicology
    Vuosikerta103
    Numero4
    Sivut367-373
    Sivumäärä7
    ISSN1742-7835
    DOI - pysyväislinkit
    TilaJulkaistu - 2008
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Lainaa tätä

    Kambur, Oleg ; Männistö, Pekka T ; Viljakka, Kaarin ; Reenilä, Ilkka ; Lemberg, Kim ; Kontinen, Vesa K ; Karayiorgou, Maria ; Gogos, Joseph ; Kalso, Eija. / Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice. Julkaisussa: Basic & Clinical Pharmacology & Toxicology. 2008 ; Vuosikerta 103, Nro 4. Sivut 367-373.
    @article{a79c27c3c2ce4a99b1d815a7029dc02c,
    title = "Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice",
    abstract = "Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.",
    author = "Oleg Kambur and M{\"a}nnist{\"o}, {Pekka T} and Kaarin Viljakka and Ilkka Reenil{\"a} and Kim Lemberg and Kontinen, {Vesa K} and Maria Karayiorgou and Joseph Gogos and Eija Kalso",
    year = "2008",
    doi = "10.1111/j.1742-7843.2008.00289.x",
    language = "English",
    volume = "103",
    pages = "367--373",
    journal = "Basic & Clinical Pharmacology & Toxicology",
    issn = "1742-7835",
    publisher = "Wiley",
    number = "4",

    }

    Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice. / Kambur, Oleg; Männistö, Pekka T; Viljakka, Kaarin; Reenilä, Ilkka; Lemberg, Kim; Kontinen, Vesa K; Karayiorgou, Maria; Gogos, Joseph; Kalso, Eija.

    julkaisussa: Basic & Clinical Pharmacology & Toxicology, Vuosikerta 103, Nro 4, 2008, s. 367-373.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice

    AU - Kambur, Oleg

    AU - Männistö, Pekka T

    AU - Viljakka, Kaarin

    AU - Reenilä, Ilkka

    AU - Lemberg, Kim

    AU - Kontinen, Vesa K

    AU - Karayiorgou, Maria

    AU - Gogos, Joseph

    AU - Kalso, Eija

    PY - 2008

    Y1 - 2008

    N2 - Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.

    AB - Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.

    U2 - 10.1111/j.1742-7843.2008.00289.x

    DO - 10.1111/j.1742-7843.2008.00289.x

    M3 - Article

    VL - 103

    SP - 367

    EP - 373

    JO - Basic & Clinical Pharmacology & Toxicology

    JF - Basic & Clinical Pharmacology & Toxicology

    SN - 1742-7835

    IS - 4

    ER -