title: Effects of treatment with a carbon monoxide-releasing molecule and a heme oxygenase 1 inducer in the antinociceptive effects of morphine in different models of acute and chronic pain in mice.
abstract: BACKGROUND
  Treatment with a carbon monoxide-releasing molecule (tricarbonyldichlororuthenium(II) dimer, CORM-2) or a classical heme oxygenase 1 inducer (cobalt protoporphyrin IX, CoPP) has potent anti-inflammatory effects, but the role played by these treatments in the antinociceptive effects of morphine during acute and chronic pain was not evaluated.
  
  
  OBJECTIVE
  In wild type (WT), neuronal (NOS1-KO), or inducible (NOS2-KO) nitric oxide synthases knockout mice, we evaluated the effects of CORM-2 and CoPP treatments in the antinociceptive actions of morphine and their interaction with nitric oxide during acute, visceral, and chronic inflammatory or neuropathic pain.
  
  
  METHODS
  Acute and visceral pain was assessed through formalin and acid acetic writhing tests. Chronic inflammatory pain induced by the intra-articular administration of complete Freund's adjuvant and neuropathic pain by partial ligation of sciatic nerve were evaluated by measuring allodynia and hyperalgesia using the von Frey filaments, plantar, or cold plate tests.
  
  
  RESULTS
  While nitric oxide, synthetized by NOS1 and/or NOS2, increased the local antinociceptive effects of morphine during acute and chronic pain, it decreased the inhibitory effects of morphine after visceral pain. Moreover, while CORM-2 or CoPP treatments did not alter or reduced the antinociceptive effects of morphine during acute and visceral pain, both treatments improved the local antiallodynic and antihyperalgesic effects of morphine after chronic inflammatory or neuropathic pain in WT, but not in KO mice.
  
  
  CONCLUSIONS
  CORM-2 and CoPP treatments improved the local antinociceptive effects of morphine during chronic inflammatory and neuropathic pain by interaction with nitric oxide synthetized by NOS1 and NOS2 isoforms.
authors.affiliation: Grup de Neurofarmacologia Molecular, Institut d'Investigació Biomèdica Sant Pau & Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Hervera
authors.forename: Gemma
authors.initials: G
authors.lastname: Gou
authors.forename: Sergi
authors.initials: S
authors.lastname: Leánez
authors.forename: Olga
authors.initials: O
authors.lastname: Pol
mesh_terms: D059787:Acute Pain / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism*; D059350:Chronic Pain / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D009942:Organometallic Compounds; D011524:Protoporphyrins; C447082:tricarbonyldichlororuthenium (II) dimer; C007095:cobaltiprotoporphyrin; D009020:Morphine; D002248:Carbon Monoxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1