title: The ruthenium NO donor, [Ru(bpy)2(NO)SO3](PF6), inhibits inflammatory pain: involvement of TRPV1 and cGMP/PKG/ATP-sensitive potassium channel signaling pathway.
abstract: The activation of nitric oxide (NO) production is an analgesic mechanism shared by drugs such as morphine and diclofenac. Therefore, the controlled release of low amounts of NO seems to be a promising analgesic approach. In the present study, the antinociceptive effect of the ruthenium NO donor [Ru(bpy)2(NO)SO3](PF6) (complex I) was investigated. It was observed that complex I inhibited in a dose (0.3-10mg/kg)-dependent manner the acetic acid-induced writhing response. At the dose of 1mg/kg, complex I inhibited the phenyl-p-benzoquinone-induced writhing response and formalin- and complete Freund's adjuvant-induced licking and flinch responses. Additionally, complex I also inhibited transient receptor potential cation channel subfamily V member 1 (TRPV1)-dependent overt pain-like behavior induced by capsaicin. Complex I also inhibited the carrageenin-induced mechanical hyperalgesia and increase of myeloperoxidase activity (MPO) in paw skin samples. The inhibitory effect of complex I in the carrageenin-induced hyperalgesia, MPO activity and formalin was prevented by the treatment with ODQ, KT5823 and glybenclamide, indicating that complex I inhibits inflammatory hyperalgesia by activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. The present study demonstrates the efficacy of a novel ruthenium NO donor and its analgesic mechanisms.
authors.affiliation: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Staurengo-Ferrari
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Mizokami
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Silva
authors.forename: Francisco O N
authors.initials: FO
authors.lastname: da Silva
authors.forename: Eduardo H S
authors.initials: EH
authors.lastname: Sousa
authors.forename: Luiz G
authors.initials: LG
authors.lastname: da França
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Matuoka
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Georgetti
authors.forename: Marcela M
authors.initials: MM
authors.lastname: Baracat
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.forename: Wander R
authors.initials: WR
authors.lastname: Pavanelli
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control*; D015221:Potassium Channels / Q000378:metabolism*; D017975:Ruthenium Compounds / Q000494:pharmacology*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: D020030:Nitric Oxide Donors; D015221:Potassium Channels; D017975:Ruthenium Compounds; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000255:Adenosine Triphosphate; D017869:Cyclic GMP-Dependent Protein Kinases; D042967:Electron Transport Complex I; D006152:Cyclic GMP