Razi Journal of Medical Sciences

    Background and Aim: Ascorbate (ascorbic acid) is present in high concentration in the nervous system and is released as a result of activation of glutaminergic neurons. Due to high concentration of NMDA receptors in the nervous system, this study investigated the analgesic efficacy of ascorbic acid (AA) in neuropathic pain condition and the role of NMDA receptors in this effect.

Materials and Methods: In this experimental study, neuropathic pain was induced by chronic constriction injury of sciatic nerve (CCI, model) in the left hind paw. In the second week after CCI, animals received 1, 5, 10 mg/kg of ascorbic acid or normal saline and pain threshold was determined 15 and 30 minutes later. To determine the role of NMDA receptor in nociceptive effect of AA, separate groups of animals were tested. In these groups in the second week after CCI, 30 min after injection of saline or AA (1mg/kg) animals received intraperitoneal injection of Ketamin (5 mg/kg) or MK-801 (0.01 mg/kg) and were tested 20 min afterwards. Mechanical allodynia was assessed by Von Frey hairs and mechanical and thermal hyperalgesia were determined by Randall Selitto and Radiant Heat tests, respectively. Data were analyzed by ANOVA and Newman Keuls tests.

Results: Intraperitoneal injection of 5 and 10 mg/kg but not 1mg/kg ascorbic acid increased mechanical and thermal threshold in the second week after CCI. Ascorbic acid (1mg/kg, i.p.) also produced significant inhibition of MK-801 and ketamin - induced antinociception response. In these groups there was no significant difference in the pain threshold as compared to animals that received normal saline.

Conclusion: The results indicate that ascorbic acid produced a dose dependent antinociceptive effect that seems to be mediated through its interaction with NMDA receptors.