Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice

Vale, Mariana Lima; Rolim, Dalila; Cavalcante, Ilane Ferreira; Ribeiro, Ronaldo A.; Souza, Marcellus H.

doi:10.1007/s00011-006-6109-8

Cited by 33 publications

(20 citation statements)

References 23 publications

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“…The opening of these channels induces the membrane hyperpolarization and reduces the depolarization and action potential transmission abilities of neurons, thereby inducing analgesia (Nguelefack et al, 2010). In the same sense, Sachs et al (2004) and Vale et al (2007) have described that NO/cGMP, PKG/ ATP pathway is an additional mechanism of action of some peripheral analgesics and this events' sequence would be considered an antagonistic mechanism to the hyperalgesic state that occurs in inflamed tissues. Then, to further understand the mechanism of action of the extract and to determine the possible participation of this pathway in the antinociception induced by Urtica circularis, its activity was evaluated in presence of l-arginine (an oxide nitric synthase substrate), l-NAME (a non-selective oxide nitric synthase inhibitor) and glibenclamide (an ATP-sensitive K + channels blocker).…”

Section: Discussionmentioning

confidence: 93%

“…), oxide nitric synthase substrate. Doses and drug administration schedules were selected based on previous reports and on pilot experiments in our laboratory (Pinardi et al, 2003;Vale et al, 2007;Bezerra et al, 2008;Guginski et al, 2009) and were administered 30 min before Urtica circularis extract (100 mg/kg, i.p.) The nociceptive response was evaluated in the acetic acid-induced abdominal writhing test.…”

Section: Acetic Acid-induced Abdominal Writhingmentioning

confidence: 99%

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Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Gorzalczany

Marrassini

Miño

et al. 2011

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 93%

Section: Acetic Acid-induced Abdominal Writhingmentioning

confidence: 99%

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Gorzalczany

Marrassini

Miño

et al. 2011

Journal of Ethnopharmacology

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“…doses of ODQ between 0.001 and 0.01 mg/kg caused a dose-related antagonism of the antinociceptive effect. By comparison, ODQ has been reported to antagonize the antinociceptive effect of sildenafil in a dose range of 0.1-1.0 mg/kg (Vale et al, 2007). The explanation for this different in antagonistic potency of ODQ is not presently known.…”

Section: Discussionmentioning

confidence: 99%

The acute antinociceptive effect of HBO2 is mediated by a NO–cyclic GMP–PKG–KATP channel pathway in mice

et al. 2011

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Previous research has found that hyperbaric oxygen (HBO 2 ) produces an acute antinociceptive effect that is dependent on nitric oxide (NO). The present study was undertaken to determine whether HBO 2 -induced acute antinociception might involve a NO-cyclic GMP-protein kinase G-ATP-sensitive potassium (K ATP ) channel pathway. Male NIH Swiss mice were subjected to a 5-min HBO 2 treatment (100% oxygen at 3.5 absolute atmospheres) and antinociception was assessed over the next 6 min still under HBO 2 using the acetic acid abdominal constriction test. Pretreatment with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO, an NO scavenger), 1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1-one) (a soluble guanylyl cyclase-inhibitor, Rp-8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphorothioate (a protein kinase G-inhibitor) or glibenclamide (an ATP-sensitive potassium channel-inhibitor) all led to antagonism of the HBO 2 -induced acute antinociception in a dose-dependent manner. These findings suggest that HBO 2 -induced acute antinociception might be due to activation of a NO-cyclic GMP-protein kinase G-K ATP channel pathway. KeywordsHyperbaric oxygen; antinociception; nitric oxide; cyclic GMP; protein kinase G; potassium channels; mice © 2010 Elsevier B.V. All rights reserved. * Corresponding author. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, WA 99164-6534, USA. Fax: +1-509-335-5902. quockr@wsu.edu (R.M. Quock).. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Research Highlights •Hyperbaric oxygen (HBO 2 ) induces antinocicepton in the mouse abdominal constriction test.• HBO 2 antinociception depends on NO, cyclic GMP, PKG and the K ATP channel.NIH Public Access

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“…The selected doses of drugs were chosen based on pilot studies and previous data of our laboratory. We detected that the doses of drugs used do not alter the nociceptive response per se , and inhibit the respective standard stimulus [16, 18, 34, 35,36, 37]…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the relevance of the antinociceptive effect of NO is already established. Furthermore, the antinociceptive effect of NO depends on formation of guanylate cyclase-derived cGMP [10], leading to the activation of cGMP-dependent protein kinase (PKG), which phosphorylates ATP-sensitive potassium channels, thereby diminishing nociceptive information transmission [9, 15, 18]…”

Section: Introductionmentioning

confidence: 99%

Nitroxyl inhibits overt pain-like behavior in mice: Role of cGMP/PKG/ATP-sensitive potassium channel signaling pathway

Staurengo‐Ferrari

Zarpelon

Longhi-Balbinot

et al. 2014

Pharmacological Reports

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Background Several lines of evidence have indicated that nitric oxide (NO) plays complex and diverse roles in modulation of pain/analgesia. However, the roles of charged and uncharged congeners of NO are less well understood. In the present study, the antinociceptive effect of the nitroxyl (HNO) donor, Angeli’s salt (Na2N2O3; AS) was investigated in models of overt pain-like behavior. Moreover, whether the antinociceptive effect of nitroxyl was dependent on the activation of cGMP (cyclic guanosine monophosphate)/PKG (protein kinase G)/ATP-sensitive potassium channels was addressed. Methods The antinociceptive effect of AS was evaluated on phenyl-p-benzoquinone (PBQ)- and acetic acid-induced writhings and via the formalin test. In addition, pharmacological treatments targeting guanylate cyclase (ODQ), PKG (KT5923) and ATP-sensitive potassium channel (glybenclamide) were used. Results PBQ and acetic acid induced significant writhing responses over 20 min. The nociceptive response in these models were significantly reduced in a dose-dependent manner by subcutaneous pre-treatment with AS. Furthermore, AS also inhibited both phases of the formalin test. Subsequently, the inhibitory effect of AS in writhing and flinching responses were prevented by ODQ, KT5823 and glybenclamide, although these inhibitors alone did not alter the writhing score. Furthermore, pretreatment with L-cysteine, an HNO scavenger, confirmed that the antinociceptive effect of AS depends on HNO. Conclusion The present study demonstrates the efficacy of a nitroxyl donor and its analgesic mechanisms in overt pain-like behavior by activating the cGMP/PKG/ATP-sensitive potassium channel (K+) signaling pathway.

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Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice

Abstract: The data indicate that the antinociceptive effect of sildenafil is dependent on the activation of the NO/cGMP/ K(ATP) pathway.

Cited by 33 publications

References 23 publications

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

The acute antinociceptive effect of HBO2 is mediated by a NO–cyclic GMP–PKG–KATP channel pathway in mice

Nitroxyl inhibits overt pain-like behavior in mice: Role of cGMP/PKG/ATP-sensitive potassium channel signaling pathway

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