Journal
NEUROPHARMACOLOGY
Volume 71, Issue -, Pages 1-9Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2013.03.009
Keywords
Nitroxyl; Angeli's salt; Nociception; Pain; Cytokine; Nitric oxide
Categories
Funding
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- Decit/SCTIE/MS (Departamento de Ciencia e Tecnologia da Secretaria de Ciencia, Tecnologia e Insumos Estrategicos, Ministerio da Saude)
- Fundacao Araucaria, Brazil
- National Institutes of Health [R01-GM076247]
- Fundacao Araucaria
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM076247] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Nitric oxide modulates pain development. However, there is no evidence on the effect of nitroxyl (HNO/NO-) in nociception. Therefore, we addressed whether nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl donor Angeli's salt (AS; Na2N2O3). Mechanical hyperalgesia was evaluated using a modified Randall and Selitto method in rats, cytokine production by ELISA and nitroxyl was determined by confocal microscopy in DAF (a cell permeable reagent that is converted into a fluorescent molecule by nitrogen oxides)-treated dorsal root ganglia neurons in culture. Local pre-treatment with AS (17-450 mu g/paw, 30 min) inhibited the carrageenin-induced mechanical hyperalgesia in a dose- and time-dependent manner with maximum inhibition of 97%. AS also inhibited carrageenin-induced cytokine production. AS inhibited the hyperalgesia induced by other inflammatory stimuli including lipopolysaccharide, tumor necrosis factor-alpha, interleukin-1 beta and prostaglandin E-2. Furthermore, the analgesic effect of AS was prevented by treatment with ODQ (a soluble guanylate cyclase inhibitor), KT5823 (a protein kinase G[PKG] inhibitor) or glybenclamide (an ATP-sensitive K+ channel blocker), but not with naloxone (an opioid receptor antagonist). AS induced concentration-dependent increase in fluorescence intensity of DAF-treated neurons in a L-cysteine (nitroxyl scavenger) sensitive manner. L-cysteine did not affect the NO donor S-Nitroso-N-acetyl-DL- penicillamine (SNAP)-induced anti-hyperalgesia or fluorescence of OAF-treated neurons. This is the first study to demonstrate that nitroxyl inhibits inflammatory hyperalgesia by reducing cytokine production and activating the cGMP/PKG/ATP-sensitive K+ channel signaling pathway in vivo. (C) 2013 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available