The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats

Ana C. Zarpelon, Guilherme R. Souza, Thiago M. Cunha, Ieda R S Schivo, Mario Marchesi, Rubia Casagrande, Phileno Pinge-Filho, Fernando Q. Cunha, Sergio H. Ferreira, Katrina M Miranda, Waldiceu A. Verri

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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; Na2N2O 3). 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 μg/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-α, interleukin-1β and prostaglandin E2. 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 DAF-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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalNeuropharmacology
Volume71
DOIs
StatePublished - Aug 2013

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Hyperalgesia
Cyclic GMP-Dependent Protein Kinases
Carrageenan
Cytokines
Neurons
Cysteine
Adenosine Triphosphate
Fluorescence
Nitrogen Oxides
Penicillamine
Nociception
Narcotic Antagonists
Glyburide
Spinal Ganglia
Protein Kinase Inhibitors
Interleukin-1
Dinoprostone
Confocal Microscopy
Analgesics
Lipopolysaccharides

Keywords

  • Angeli's salt
  • Cytokine
  • Nitric oxide
  • Nitroxyl
  • Nociception
  • Pain

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Zarpelon, A. C., Souza, G. R., Cunha, T. M., Schivo, I. R. S., Marchesi, M., Casagrande, R., ... Verri, W. A. (2013). The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats. Neuropharmacology, 71, 1-9. https://doi.org/10.1016/j.neuropharm.2013.03.009

The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats. / Zarpelon, Ana C.; Souza, Guilherme R.; Cunha, Thiago M.; Schivo, Ieda R S; Marchesi, Mario; Casagrande, Rubia; Pinge-Filho, Phileno; Cunha, Fernando Q.; Ferreira, Sergio H.; Miranda, Katrina M; Verri, Waldiceu A.

In: Neuropharmacology, Vol. 71, 08.2013, p. 1-9.

Research output: Contribution to journalArticle

Zarpelon, AC, Souza, GR, Cunha, TM, Schivo, IRS, Marchesi, M, Casagrande, R, Pinge-Filho, P, Cunha, FQ, Ferreira, SH, Miranda, KM & Verri, WA 2013, 'The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats', Neuropharmacology, vol. 71, pp. 1-9. https://doi.org/10.1016/j.neuropharm.2013.03.009
Zarpelon AC, Souza GR, Cunha TM, Schivo IRS, Marchesi M, Casagrande R et al. The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats. Neuropharmacology. 2013 Aug;71:1-9. https://doi.org/10.1016/j.neuropharm.2013.03.009
Zarpelon, Ana C. ; Souza, Guilherme R. ; Cunha, Thiago M. ; Schivo, Ieda R S ; Marchesi, Mario ; Casagrande, Rubia ; Pinge-Filho, Phileno ; Cunha, Fernando Q. ; Ferreira, Sergio H. ; Miranda, Katrina M ; Verri, Waldiceu A. / The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats. In: Neuropharmacology. 2013 ; Vol. 71. pp. 1-9.
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AU - Schivo, Ieda R S

AU - Marchesi, Mario

AU - Casagrande, Rubia

AU - Pinge-Filho, Phileno

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KW - Nociception

KW - Pain

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