Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats

Objective(s): Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fu...

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Main Authors: Siavash Parvardeh, Masoumeh Sabetkasaei, Mahsa Moghimi, Alireza Masoudi, Shiva Ghafghazi, Fatemeh Mahboobifard
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2018-06-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:http://ijbms.mums.ac.ir/article_10674_5d52f7d71006d038714fcf4f7dc1307c.pdf
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author Siavash Parvardeh
Masoumeh Sabetkasaei
Mahsa Moghimi
Alireza Masoudi
Shiva Ghafghazi
Fatemeh Mahboobifard
author_facet Siavash Parvardeh
Masoumeh Sabetkasaei
Mahsa Moghimi
Alireza Masoudi
Shiva Ghafghazi
Fatemeh Mahboobifard
author_sort Siavash Parvardeh
collection DOAJ
description Objective(s): Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.Materials and Methods: Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone. Results: Local ipsilateral (20 and 40 μg, IPL) but not contralateral and ICV (4 and 8 μg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 μg, IPL or ICV) and SNAP (200 μg, IPL or ICV) increased while l-NAME (100 μg, IPL or 1 μg, ICV) and methylene blue (400 μg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 μg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test. Conclusion: The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.
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spelling doaj.art-e0ed57583dd74180abc119016bd89a972022-12-21T23:37:15ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742018-06-0121662563310.22038/ijbms.2018.26255.643810674Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in ratsSiavash Parvardeh0Masoumeh Sabetkasaei1Mahsa Moghimi2Alireza Masoudi3Shiva Ghafghazi4Fatemeh Mahboobifard5Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranObjective(s): Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.Materials and Methods: Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone. Results: Local ipsilateral (20 and 40 μg, IPL) but not contralateral and ICV (4 and 8 μg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 μg, IPL or ICV) and SNAP (200 μg, IPL or ICV) increased while l-NAME (100 μg, IPL or 1 μg, ICV) and methylene blue (400 μg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 μg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test. Conclusion: The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.http://ijbms.mums.ac.ir/article_10674_5d52f7d71006d038714fcf4f7dc1307c.pdfGuanylyl cyclaseNitric oxidePain signalingPotassium channelsThymoquinone
spellingShingle Siavash Parvardeh
Masoumeh Sabetkasaei
Mahsa Moghimi
Alireza Masoudi
Shiva Ghafghazi
Fatemeh Mahboobifard
Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
Iranian Journal of Basic Medical Sciences
Guanylyl cyclase
Nitric oxide
Pain signaling
Potassium channels
Thymoquinone
title Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
title_full Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
title_fullStr Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
title_full_unstemmed Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
title_short Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
title_sort role of l arginine no cgmp katp channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats
topic Guanylyl cyclase
Nitric oxide
Pain signaling
Potassium channels
Thymoquinone
url http://ijbms.mums.ac.ir/article_10674_5d52f7d71006d038714fcf4f7dc1307c.pdf
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