Bahareh Naghizadeh1, Mohammad Taghi Mansouri2, Behnam Ghorbanzadeh3. 1. a Department of Pharmacology , Medical School, Pain and Physiology Research Centers, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran . 2. b Department of Pharmacology , Medical School, Physiology and Atherosclerosis Research Centers, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran , and. 3. c Department of Pharmacology , Medical School, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran.
Abstract
CONTEXT: Ellagic acid (EA) produced antinociceptive and anti-inflammatory effects through the central and peripheral sites of action. OBJECTIVE: The objective of the current study was to examine the functional interaction between ellagic acid and carbamazepine (CBZ) on pain. MATERIALS AND METHODS: Fourteen groups of mice (8-10 each) were used in this study. Pain was induced by intraperitoneal acetic acid in mice (writhing test) and the functional interaction was analyzed using the isobolographic method. EA at doses 0.3, 1, 3, and 10 mg/kg and carbamazepine at doses 3, 10, 20, and 30 mg/kg, alone and also in combination (1/2, 1/4, and 1/8 of the drug's ED50) were intraperitoneally administered 30 min before acetic acid (0.6% v/v). Then, the abdominal writhes were counted during a 25-min period. RESULTS: EA (0.3-10 mg/kg, i.p.) and CBZ (3-30 mg/kg, i.p.) inhibited the writhing response evoked by acetic acid. Fifty percent effective dose (ED50) values against this tonic pain were 1.02 mg/kg and 6.40 mg/kg for EA and CBZ, respectively. The antinociception induced by EA showed higher potency than that of carbamazepine. Co-administration of increasing fractional increments of ED50 values of EA and CBZ produced additive interaction against writhing responses, as revealed by isobolographic analysis. DISCUSSION AND CONCLUSION: These results suggest that a combination of carbamazepine and ellagic acid may be a new strategy for the management of neuropathic pain such as what occurs in trigeminal neuralgia, since the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic effect through microsomal enzyme induction.
CONTEXT: Ellagic acid (EA) produced antinociceptive and anti-inflammatory effects through the central and peripheral sites of action. OBJECTIVE: The objective of the current study was to examine the functional interaction between ellagic acid and carbamazepine (CBZ) on pain. MATERIALS AND METHODS: Fourteen groups of mice (8-10 each) were used in this study. Pain was induced by intraperitoneal acetic acid in mice (writhing test) and the functional interaction was analyzed using the isobolographic method. EA at doses 0.3, 1, 3, and 10 mg/kg and carbamazepine at doses 3, 10, 20, and 30 mg/kg, alone and also in combination (1/2, 1/4, and 1/8 of the drug's ED50) were intraperitoneally administered 30 min before acetic acid (0.6% v/v). Then, the abdominal writhes were counted during a 25-min period. RESULTS:EA (0.3-10 mg/kg, i.p.) and CBZ (3-30 mg/kg, i.p.) inhibited the writhing response evoked by acetic acid. Fifty percent effective dose (ED50) values against this tonic pain were 1.02 mg/kg and 6.40 mg/kg for EA and CBZ, respectively. The antinociception induced by EA showed higher potency than that of carbamazepine. Co-administration of increasing fractional increments of ED50 values of EA and CBZ produced additive interaction against writhing responses, as revealed by isobolographic analysis. DISCUSSION AND CONCLUSION: These results suggest that a combination of carbamazepine and ellagic acid may be a new strategy for the management of neuropathic pain such as what occurs in trigeminal neuralgia, since the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic effect through microsomal enzyme induction.