The role of gaseous neurotransmitters in the antinociceptive effects of morphine during acute thermal pain.
Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer, CORM-2) or a classical inducible heme oxygenase (HO-1) inducer (cobalt protoporphyrin IX, CoPP) enhanced the antinociceptive effects of morphine during chronic pain but the role played by these compounds in acute thermal nociception was not evaluated. The effects of CORM-2 and CoPP treatments on the local antinociceptive actions of morphine and their interactions with nitric oxide during acute pain were evaluated by using wild type (WT), neuronal (nNOS-KO) or inducible (iNOS-KO) nitric oxide synthase knockout mice and assessing their thermal nociception to a hot stimulus with the hot plate test. Our results showed that the absence of nNOS or iNOS genes did not alter licking and jumping responses nor the antinociceptive effects produced by morphine indicating that the local thermal inhibitory effects produced by this drug in the absence of inflammation or injury are not mediated by the nitric oxide pathway triggered by nNOS or iNOS enzymes. Moreover, while the systemic administration of CORM-2 or CoPP inhibited licking and jumping latencies in all genotypes, these treatments only enhanced the local inhibition of jumping latencies produced by morphine in WT and nNOS-KO mice which effects were reversed by the peripheral administration of an HO-1 inhibitor. These data indicate that the co-administration of morphine with CORM-2 or CoPP produced remarkable local antinociceptive effects in WT and nNOS-KO mice and reveal that a significant interaction between carbon monoxide and nitric oxide systems occurs on the local antinociceptive effects produced by morphine during acute thermal nociception.
Grup de Neurofarmacologia Molecular, Institut d׳Investigació Biomèdica Sant Pau & Institut de Neurociències, Universitat Autònoma de Barcelona, Facultat de Medicina. Edifici M2-115, Barcelona 08193, Spain.
Gemma
G
Gou
Grup de Neurofarmacologia Molecular, Institut d׳Investigació Biomèdica Sant Pau & Institut de Neurociències, Universitat Autònoma de Barcelona, Facultat de Medicina. Edifici M2-115, Barcelona 08193, Spain.
Sergi
S
Leánez
Grup de Neurofarmacologia Molecular, Institut d׳Investigació Biomèdica Sant Pau & Institut de Neurociències, Universitat Autònoma de Barcelona, Facultat de Medicina. Edifici M2-115, Barcelona 08193, Spain. Electronic address: opol@santpau.es.
Olga
O
Pol
D059787:Acute Pain / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D004357:Drug Synergism; D055786:Gene Knockout Techniques; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics; D059225:Nociception / Q000187:drug effects*; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature
D000700:Analgesics; D008565:Membrane Proteins; D008665:Metalloporphyrins; D018377:Neurotransmitter Agents; D009942:Organometallic Compounds; D011524:Protoporphyrins; C447082:tricarbonyldichlororuthenium (II) dimer; C007095:cobaltiprotoporphyrin; D009020:Morphine; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
Antinociception; Carbon monoxide; Morphine; Nitric oxide; Pain; Thermal nociception