title: Central and peripheral antinociceptive effects of ellagic acid in different animal models of pain.
abstract: The present study was conducted to evaluate the analgesic effects of p.o., i.p., or i.c.v. administration of ellagic acid (EA), and investigate the possible mechanisms underlying the systemic antinociceptive activities in different animal models of pain. Using radiant heat tail-flick test, EA (100-1000 μmol/kg, retain-->p.o.) only resulted in antinociception at 1000 μmol/kg. Also, EA (10-660 μmol/kg, i.p.) produced the antinociceptive effect in a dose-dependent manner with an ED50 of 122 μmol/kg. In addition, the i.c.v. administration of EA (0.1-2 μmol/rat) resulted in dose-dependent antinociception with an ED50 of 0.33 μmol/rat. EA induced antinociception (330 μmol/kg. i.p.) was reversed by naloxone (1 mg/kg, i.p.). Likewise, EA (1-33 μmol/kg, i.p.) produced significant dose-dependent antinociception when assessed using acetic acid-induced abdominal writhing test with an ED50 of 3.5 μmol/kg. It was also demonstrated that pre-treatment with L-arginine (100mg/kg, i.p.), a nitric oxide (NO) precursor, and methylene blue (20 mg/kg, i.p.), a guanylate cyclase (GC) inhibitor, significantly enhanced antinociception produced by EA suggesting the involvement of L-arginine-NO-cGMP pathway. Additionally, administration of glibenclamide (10mg/kg, i.p.), an ATP-sensitive K(+) channel blocker, significantly reversed antinociceptive activity induced by EA. Moreover, EA treatment had no effect on the motor activity of rats when tested in rota-rod task. The present results indicate that the dose-related antinociceptive action of EA has both peripheral and central components which involve mediation by opioidergic system and L-arginine-NO-cGMP-ATP sensitive K(+) channels pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran. smt_mansouri@yahoo.com
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghi Mansouri
authors.forename: Bahareh
authors.initials: B
authors.lastname: Naghizadeh
authors.forename: Behnam
authors.initials: B
authors.lastname: Ghorbanzadeh
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Farbood
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D004610:Ellagic Acid