Abstract | RATIONALE: OBJECTIVES AND METHODS: The antiallodynic and antihyperalgesic effects of a carbon monoxide releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), daily administered from days 4 to 14 after complete Freund's adjuvant (CFA) injection in wild-type (WT), neuronal (NOS1-KO), and inducible (NOS2-KO) nitric oxide synthases knockout mice, were evaluated using von Frey filaments and plantar tests. Effects of CORM-2 treatment on the expression of HO-1, NOS1, and NOS2 at 14 days after inflammation induction were assessed by Western blot. RESULTS: Main inflammatory pain symptoms induced by CFA in WT, NOS1-KO, and NOS2-KO mice were significantly reduced in a time-dependent manner by CORM-2 treatment. In all genotypes, inflammation increased the dorsal root ganglia and paw expression of HO-1, but CORM-2 treatment only over-expressed this enzyme in the paw of all genotypes. The increased NOS1 expression induced by inflammation in WT mice was abolished by CORM-2 treatment, while there was no effect of the inflammation in neither CORM-2 treatment in the expression of NOS2 in WT and NOS1-KO mice. CONCLUSIONS:
CORM-2 treatment inhibits inflammatory pain through enhancing HO-1 paw expression in all genotypes and reducing NOS1 over-expression in WT mice. An interaction between HO-1/ carbon monoxide and NOS1/ nitric oxide systems was also demonstrated. CORM-2 treatment may represent a new approach for management chronic inflammatory pain.
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Authors | Roger Negrete, Arnau Hervera, Sergi Leánez, Olga Pol |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 231
Issue 5
Pg. 853-61
(Mar 2014)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 24114430
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Membrane Proteins
- Organometallic Compounds
- tricarbonyldichlororuthenium (II) dimer
- Nitric Oxide
- Carbon Monoxide
- Freund's Adjuvant
- Nitric Oxide Synthase Type I
- Nitric Oxide Synthase Type II
- Nos1 protein, mouse
- Nos2 protein, mouse
- Heme Oxygenase-1
- Hmox1 protein, mouse
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Topics |
- Animals
- Carbon Monoxide
(pharmacokinetics, pharmacology)
- Chronic Pain
(drug therapy, enzymology, etiology, metabolism)
- Freund's Adjuvant
(pharmacology)
- Heme Oxygenase-1
(biosynthesis, metabolism)
- Hyperalgesia
(chemically induced, drug therapy, enzymology, metabolism)
- Inflammation
(complications)
- Male
- Membrane Proteins
(biosynthesis, metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type I
(biosynthesis, metabolism)
- Nitric Oxide Synthase Type II
(biosynthesis, metabolism)
- Organometallic Compounds
(pharmacokinetics, pharmacology)
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