Ellagic acid enhances the antinociceptive action of venlafaxine in mouse acetic acid-induced pain: An isobolographic analysis.
BACKGROUND
Several antidepressants have been used to treat severe pain in clinics. Recently, it has been shown that ellagic acid (EA), a major constituent of pomegranate juice, produced antinociceptive and anti-inflammatory effect through the central and peripheral sites of action.


METHODS
In this study, we examined the interaction between EA and venlafaxine (VLF) on pain induced by intraperitoneal acetic acid in mice using isobolographic analysis.


RESULTS
EA (0.3-10mg/kg, ip) and VLF (3-60 mg/kg, ip) produced a dose-dependent inhibition of the writhing response evoked by acetic acid. Fifty percent effective dose (ED50) values against writhing behaviors were 1.02 (0.86-1.19)mg/kg and 12.37 (9.74-15.37)mg/kg for EA and VLF, respectively, and also with higher potency than that of VLF. Co-administration of increasing fractional increments of ED50 doses of EA and VLF produced synergistic interaction against writhing behaviors, as revealed by isobolographic analysis.


CONCLUSIONS
The synergistic action of EA and VLF provides valuable tool referring to the management of visceral pain.
Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran. Electronic address: mansouri_smt@yahoo.com.
Mohammad Taghi
MT
Mansouri
Department of Pharmacology, School of Medicine, Pain and Physiology Research Centers, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
Bahareh
B
Naghizadeh
Department of Pharmacology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
Behnam
B
Ghorbanzadeh
D019342:Acetic Acid / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004610:Ellagic Acid / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods*; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage*
D004610:Ellagic Acid; D000069470:Venlafaxine Hydrochloride; D019342:Acetic Acid
Antinociception; Ellagic acid; Isobolographic; Venlafaxine; Writhing test