Ascorbic Acid Interaction With Analgesic Effect of Morphine and Tramadol in Mice

Abstract

Background:Combining different analgesic drugs for improvement of drug efficacy is a recommended strategy intended to achieve the optimal therapeutic effects.Objectives:The purpose of the present study was to assess the nature of the interaction between ascorbic acid and two analgesic drugs, morphine and tramadol.Materials and Methods:The analgesic activity was assessed by the acetic acid writhing test in male Naval Medical Research Institute (NMRI) mice. The results were obtained using four to six animals in each group. All the drugs were injected intraperitoneally. The effective doses (ED) that produced 20%, 50%, and 65% antinociception (ED20, ED50 and ED65) were calculated from the dose-response curve of each drug alone as well as co-administration of ascorbic acid and tramadol or morphine. The interaction index was calculated as experimental ED/theoretical ED. For each drug combination, ED50, ED20 and ED65 were determined by linear regression analysis of the dose-response curve, and they were compared to theoretical ED50, ED20 and ED65 using t-test.Results:The antinociceptive effects of all drugs were dose-dependent (ED50was 206.1 mg/kg for ascorbic acid, 8.33 mg/kg for tramadol, and 0.79 mg/kg for morphine). The interaction index demonstrated additive effects at ED50 and ED65 for co-administration of ascorbic acid and tramadol or morphine. However, at ED20, combination of ascorbic acid and tramadol or morphine showed synergic effects. The interaction index values of the combinations demonstrated the potency ratio of ascorbic acid/morphine to be lower than ascorbic acid/tramadol.Conclusions:This study demonstrated the results of interactions between ascorbic acid and tramadol or morphine. The results showed that the interaction effects on antinociception may be synergistic or additive, depending on the level of effect.

The Analgesic Effects of Morphine and Tramadol Added to Intra-articular Levobupivacaine-Tenoxicam Combination for Arthroscopic Knee Surgery on Postoperative Pain; a Randomized Clinical Trial

“…Combining tramadol or morphine with other drugs can decrease the high postoperative dosages of administered opiates and thus, can lead to less drug adverse effects ( 4 , 36 ). Several studies have suggested ways to manage postoperative pain after arthroscopy, some of which are IA injection of different drugs combination.…”

Ascorbic acid for management of oral surgery pain not responding to conventional medication: case report

“…Two case reports and a cohort study from Schencking et al described clinical improvement and relief of pain for patients with acute herpes zoster exacerbation who received L-ascorbic acid [27,28]. Double-blind placebo-controlled study revealed that the duration of pain caused by labial herpes was shortened by 51%, when patients were administered 1 g/day of L-ascorbic acid together with bioflavonoids [29]. Ascorbate treatment also resulted in a better efficacy than placebo in pain modulation in post herpetic neuralgia (PHN) and intravenous ascorbate helps relieve spontaneous pain in PHN [30,31].…”

Vitamin C

“…Combination of vitamin C supplements with aspirin and opiates has a strong synergistic effect on these drugs [54,74]. On the other hand, oral contraceptive pills increases ascorbic acid turnover and reduce level of ascorbic acid [75].…”