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 RESEARCH ARTICLE
Year : 2014  |  Volume : 46  |  Issue : 4  |  Page : 404-408

Sildenafil enhances the peripheral antinociceptive effect of ellagic acid in the rat formalin test


1 Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers; Pain and Physiology Research Centers, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers; Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Correspondence Address:
Mohammad Taghi Mansouri
Department of Pharmacology, School of Medicine, Physiology and Atherosclerosis Research Centers; Pain and Physiology Research Centers, Ahvaz Jundishapur University of Medical Sciences, Ahvaz
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.135952

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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.






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