Repository of Research and Investigative Information

Repository of Research and Investigative Information

Dezful University of Medical Sciences

Involvement of the L-arginine/Nitric Oxide/Cyclic GMP/K ATP Channel Pathway and PPARγ Receptors in the Peripheral Antinociceptive Effect of Carbamazepine

(2019) Involvement of the L-arginine/Nitric Oxide/Cyclic GMP/K ATP Channel Pathway and PPARγ Receptors in the Peripheral Antinociceptive Effect of Carbamazepine. Drug Research. pp. 650-657. ISSN 21949379 (ISSN)

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Carbamazepine has been shown to exert analgesic effects in clinical and experimental pain situation. This study was conducted to evaluate its potential peripheral antinociceptive effects and the possible involvement of L-arginine/NO/cGMP/K ATP channel pathway and PPARγ receptors in an animal model of pain. The antinociceptive effect induced by intraplantar administration of carbamazepine (100-1 000 μg/paw) was assessed using the formalin test in rats. To evaluate the involvement of L-arginine/NO/cGMP/K ATP channel pathway in the antinociceptive action of carbamazepine, rats were pre-treated intraplantarlly with L-arginine (a nitric oxide precursor, 100 and 200 μg/paw), L-NAME (NOS inhibitor, 50 and 100 μg/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 μg/paw), glibenclamide (K ATP channel blocker, 100 and 200 μg/paw), and diazoxide (400 μg/paw). Moreover, to investigate the possible involvement of PPARγ receptors, pioglitazone (10 μg/paw; a PPARγ agonist) alone or in combination with GW9662 (3 μg/paw; a PPARγ antagonist) were pre-treated with carbamazepine. The local ipsilateral, but not contralateral, administration of carbamazepine into the hind paw produced dose-related analgesia during both early and late phases of formalin test. Moreover, pre-treatment with L-NAME, methylene blue, and glibenclamide dose-dependently prevented carbamazepine (300 μg/paw)-induced antinociception in both phases of the test. In addition, administration of L-arginine and diazoxide before the sub-effective dose of carbamazepine (100 μg/paw) produced an antinociceptive effect. Also, antinociception induced by carbamazepine plus pioglitazone (10 μg/paw) was blocked by GW-9662 in both phases of the test. In conclusion, carbamazepine induced a peripheral antinociceptive effect through PPARγ receptors and L-arginine/NO/cGMP/K ATP channel pathway, with potential for a new topical analgesic drug. © 2019 Georg Thieme Verlag. All rights reserved.

Item Type: Article
Keywords: carbamazepine formalin test L-arginine/NO/cGMP/K ATP channel local antinociception PPARγ receptors rat 2 chloro 5 nitrobenzanilide adenosine triphosphate sensitive potassium channel arginine cyclic GMP diazoxide glibenclamide guanylate cyclase methylene blue n(g) nitroarginine methyl ester nitric oxide peroxisome proliferator activated receptor gamma pioglitazone analgesia analgesic activity animal experiment animal model animal tissue Article controlled study dose response drug antagonism experimental pain intraplantar drug administration male nonhuman signal transduction
Subjects: QV Pharmacology > QV 120-140 Autonomic Agents. Nonmetallic Elements. Neuromuscular Agents
QV Pharmacology > QV 76-113 Central Nervous System Agents. Local Anesthetics
Divisions: Education Vice-Chancellor Department > Faculty of Pharmacy > Department of Toxicology and Pharmacology
Page Range: pp. 650-657
Journal or Publication Title: Drug Research
Journal Index: Scopus
Volume: 69
Number: 12
Identification Number: https://doi.org/10.1055/a-0959-5896
ISSN: 21949379 (ISSN)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.dums.ac.ir/id/eprint/617

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