Opioid and CB1 receptors involvement in central anti-nociceptive effect of vitamin C in the formalin-induced pain model in rats

Although the analgesic effect of vitamin C was reported in several studies, its supra-spinal analgesia and the involved mechanisms have not been investigated yet. In this study, central effect of vitamin C in formalin-induced pain was investigated. Naloxone (an opioid receptor antagonist) and AM251 (a CB1 receptor antagonist) were used to clarify the possible mechanism of this vitamin.

In ketamine-xylazine anesthetized rats, one stainless-steel guide cannula was implanted into the fourth ventricle of the brain. The formalin test was induced by intra-plantar injection of formalin (50 mL, 2.5%), and the time spent licking and biting of the injected paw was recorded for 1 h.

A marked biphasic (first phase: 0–5 min and second phase: 15–50 min) pain response was induced after formalin injection. Intra-fourth ventricle injection of vitamin C significantly (p < 0.05) decreased both phases of pain. Naloxone and AM251 had no effect on the pain intensity. However, the analgesic effect of vitamin C was inhibited by pretreatments  with  naloxone and AM251. All the above-mentioned treatments did not alter locomotor activity of the animals.

These results showed that vitamin C suppresses formalin-induced neurogenic and inflammatory pains in rats through central modulatory mechanisms. Opioid and cannabinoid receptors play a role in the analgesic effects of vitamin C.