title: Involvement of L-arginine/NO/cGMP/K(ATP) channel pathway in the peripheral antinociceptive actions of ellagic acid in the rat formalin test.
abstract: The present study was conducted to evaluate the local antinociceptive actions of EA and the possible involvement of l-arginine/NO/cGMP/KATP channel pathway in this effect using formalin test in rats. To evaluate the involvement of l-arginine/NO/cGMP/KATP channel pathway in the antinociceptive action of EA, rats were pre-treated intraplantarlly with l-NAME (NOS inhibitor, 25-100μg/paw), methylene blue (guanylyl cyclase inhibitor, 100-400μg/paw), glibenclamide (ATP-sensitive K(+) channel blocker, 25-100μg/paw), l-arginine (a nitric oxide precursor, 25-100μg/paw) and sodium nitroprusside (125-500μg/paw). The local peripheral ipsilateral, but not contralateral, administration of EA into the right paw (30-300μg/paw) produced a dose-related antinociception during both early and late phases of formalin test which is comparable with morphine (25μg/paw). Moreover, local pre-treatment with l-NAME, methylene blue and glibenclamide dose-dependently prevented EA (100μg/paw)-induced antinociception in late phase. Additionally, administration of l-arginine and sodium nitroprusside significantly potentiated the antinociception induced by EA in the late phase. However, these treatments had no significant effect on antinociceptive response of EA in the early phase of the formalin test. The results of the present study showed that EA-induced local peripheral antinociception during the both phases of formalin test. Also, our data suggested the activation of the l-arginine/NO/cGMP/KATP channels pathway in EA-induced antinociception in late phase of formalin test. Topical application of EA by ointment or jelly might be a useful method to relieving the inflammatory pain states.
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur Univ. of Med. Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Ghorbanzadeh
authors.affiliation: Dept. of Pharmacology, Physiology and Atherosclerosis Research Centers, School of Medicine, Ahvaz Jundishapur Univ. of Med. Sciences (AJUMS), Ahvaz, Iran. Electronic address: mansouri_smt@yahoo.com.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Mansouri
authors.affiliation: Dept. of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur Univ. of Med. Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Hemmati
authors.affiliation: Dept. of Pharmacology, Pain and Physiology Research Centers, School of Medicine, Ahvaz Jundishapur Univ. of Med. Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Naghizadeh
authors.affiliation: Dept. of Physiology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur Univ. of Med. Sciences (AJUMS), Ahvaz, Iran.
authors.forename: Seyyed Ali
authors.initials: SA
authors.lastname: Mard
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Shahid Chamran, Ahvaz, Iran.
authors.forename: Anahita
authors.initials: A
authors.lastname: Rezaie
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004610:Ellagic Acid / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000700:Analgesics; D054086:KATP Channels; D009599:Nitroprusside; D004610:Ellagic Acid; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D006152:Cyclic GMP; D005905:Glyburide; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester
keywords: Ellagic acid; Formalin; Peripheral antinociception; Rat; l-arginine/NO/cGMP/K(ATP)