Antinociceptive Properties of Ascorbic Acid: Evidence for the Mechanism of Action

Background: Ascorbic acid is amongst important water-soluble vitamins and when used orally in high-doses it has been observed to relieve pain and reduce opioid use in patients. However no controlled trial has compared the antinociceptive effects of ascorbic acid with other analgesic groups on animal models, and investigated the involved mechanisms. Objectives: In the present study, the antinociceptive effect of vitamin C on male mice was investigated and compared with morphine and diclofenac. Also, possible mechanisms were assayed. Materials and Methods: Male albino mice were used in this study. Antinociception was measured using the writhing test, tail flick and formalin tests. Ascorbic acid was used in three doses (۳۰, ۱۵۰ and ۳۰۰ mg/kg, IP) and compared with the antinociceptive effects of ۱۰ mg/kg of morphine as an opioid analgesic agent and ۵-۱۰ mg/kg of diclofenac as a nonsteroidal anti-inflammatory drug (NSAID) analgesic agent. The antinociceptive effect of ascorbic acid (۳۰۰ mg/kg) was compared before and after treatment with naloxone (۴ mg/kg), ondansetron (۰.۵ mg/kg), atropine (۵ mg/kg) and metoclopramide (۱ mg/kg) in the writhing test. Results: Vitamin C caused dose-dependent antinociceptive effects in acetic acid writhing test (P < ۰.۰۵). It had no significant effect in the tail flick test. Meanwhile, vitamin C in high doses reduced pain in the second phase of the formalin test (P < ۰.۰۵). Morphine had higher nociceptive effects in comparison to ascorbic acid in the writhing test (P < ۰.۰۵). In the second phase of the formalin test the antinociceptive effects of vitamin C (۳۰۰ mg/kg) was not significantly different with morphine at dose of ۱۰ mg/kg. There was not significant difference between vitamin C (۳۰۰ mg/kg) and diclofenac (۱۰ mg/kg) in the second phase of the formalin test. Metoclopramide and ondansetrone reduced the antinociceptive effects of vitamin C. Conclusions: The results obtained from the acetic acid induced writhing test and second phase of the formalin test indicate that vitamin C possess antinociceptive activity especially on inflammatory pain. Ondansetrone and metoclopramide reduced the effects of ascorbic acid, which may be because ascorbic acid produced antinociception through mechanisms that may be involved in dopaminergic and serotoninergic systems.