Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice.
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.
Kambur
Oleg
O
Department of Pharmacology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland. oleg.kambur@helsinki.fi
Männistö
Pekka T
PT
Viljakka
Kaarin
K
Reenilä
Ilkka
I
Lemberg
Kim
K
Kontinen
Vesa K
VK
Karayiorgou
Maria
M
Gogos
Joseph A
JA
Kalso
Eija
E
D000698:Analgesia; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000172:deficiency* / Q000235:genetics; D004361:Drug Tolerance / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000235:genetics; D013550:Swimming
D000701:Analgesics, Opioid; D015306:Biogenic Monoamines; D009020:Morphine; D002394:Catechol O-Methyltransferase