Abstract
Introduction: Combination therapies have long been used to treat painful conditions while reducing side effects. Recently, we have reported the central and peripheral antinociceptive effects of ellagic acid (a polyphenol compound in pomegranates, grapes and different berries). The present study aimed to evaluate the therapeutic potential of combination treatment with ellagic acid (EA) and nonsteroidal anti-inflammatory drugs (NSAIDs) in a visceral model of pain.
Materials and Methods: The abdominal writhing test was selected as a model of visceral inflammatory pain. Different doses of EA, indomethacin, celecoxib and acetaminophen alone or in combination with EA were administered.
Results: Data showed that EA at doses 1–10 mg/kg i.p. significantly reduced the writhes’ number induced by acetic acid in mice. Moreover, intraperitoneal administration of indomethacin at 3, 10 mg/kg, celecoxib at 10, 30 mg/kg, and acetaminophen at 200, 300 mg/kg, significantly reduced the writhing reaction. On the other hand, combination of sub-effective dose of EA (0.3 mg/kg; i.p.) with sub-analgesic doses of indomethacin (0.3, 1 mg/kg; i.p.), celecoxib (1, 3 mg/kg; i.p.) and acetaminophen (60, 100 mg/kg; i.p.) significantly decreased the number of writhes as compared to the per se effect.
Conclusions: These results indicate that EA markedly potentiates the antinociceptive activity of NSAIDs in visceral pain model. Further, these results suggest that the described combination therapies would be effective as an alternative to conventional NSAIDs and may lower incidence of their adverse effects.
Materials and Methods: The abdominal writhing test was selected as a model of visceral inflammatory pain. Different doses of EA, indomethacin, celecoxib and acetaminophen alone or in combination with EA were administered.
Results: Data showed that EA at doses 1–10 mg/kg i.p. significantly reduced the writhes’ number induced by acetic acid in mice. Moreover, intraperitoneal administration of indomethacin at 3, 10 mg/kg, celecoxib at 10, 30 mg/kg, and acetaminophen at 200, 300 mg/kg, significantly reduced the writhing reaction. On the other hand, combination of sub-effective dose of EA (0.3 mg/kg; i.p.) with sub-analgesic doses of indomethacin (0.3, 1 mg/kg; i.p.), celecoxib (1, 3 mg/kg; i.p.) and acetaminophen (60, 100 mg/kg; i.p.) significantly decreased the number of writhes as compared to the per se effect.
Conclusions: These results indicate that EA markedly potentiates the antinociceptive activity of NSAIDs in visceral pain model. Further, these results suggest that the described combination therapies would be effective as an alternative to conventional NSAIDs and may lower incidence of their adverse effects.
Keywords
Copyright
© 2018, Jundishapur Journal of Physiology. This open-access article is available under the Creative Commons Attribution-NonCommercial 4.0 (CC BY-NC 4.0) International License (https://creativecommons.org/licenses/by-nc/4.0/), which allows for the copying and redistribution of the material only for noncommercial purposes, provided that the original work is properly cited.