Sildenafil enhances the peripheral antinociceptive effect of ellagic acid in the rat formalin test |
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| Authors: | Mohammad Taghi Mansouri Bahareh Naghizadeh Behnam Ghorbanzadeh |
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| Affiliation: | 1.Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;2.Pain and Physiology Research Centers, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;3.Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran |
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| Abstract: | Objective:Ellagic acid (EA), a major polyphenolic compound of pomegranate juice, produces antinociceptive effects, which are mediated through opioidergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways. The present study was conducted to elucidate the peripheral antinociceptive effect of EA alone and in combination with sildenafil in the rat formalin test.Materials and Methods:Pain was produced by intraplantar injection of formalin (2.5%) in rats and nociceptive behavior was measured as the number of flinches every 5 min in 60 min after injection.Results:Local administration of EA and sildenafil dose-dependently increased the nociception threshold in both phases of the test. Moreover, sub-effective doses of sildenafil (25 or 50 mcg/paw, i.p.) significantly and dose-dependently enhanced the antinociception induced by a sub-effective dose of EA (60 mcg/paw, i.pl.) in both phases of the test. The antinociception produced by these drugs alone, or in combination, was due to a peripheral site of action, since the administration in the contralateral paw was ineffective.Conclusion:Our results suggest that EA has local peripheral antinociceptive activity, and enhancement of this effect with sildenafil probably occurs through the inhibition of cGMP metabolism.KEY WORDS: Ellagic acid, formalin, peripheral antinociception, sildenafil |
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