Cannabidiol microinjection into the nucleus accumbens attenuated nociceptive behaviors in an animal model of tonic pain

Cannabidiol, the major non-psychoactive constituent of Cannabis, has attracted much attention as a therapeutic agent for intractable chronic pain in many conditions. Nucleus accumbens (NAc) as a major site of action of cannabinoids is one of the main mediators of several analgesic agents especially in the persistent pain condition. The present study aimed to investigate the effect of cannabidiol microinjection into the NAc on the modulation of nociception induced by formalin injection into the rat’s paw. Adult male Wistar rats weighing 220-250 g were underwent stereotaxic surgery for unilateral (right or left side) cannula placement into the NAc. After one week recovery period, intra-NAc administration of the cannabidiol or its vehicle, DMSO was performed in a volume of 0.5 µl, five minutes before the formalin test. The formalin test was performed using 50 µl injection of formalin (2.5%) into the plantar surface of the rat’s hind paw. Intra-accumbal administration of cannabidiol attenuated the nociceptive responses during the early and late phases of the formalin test in a dose-dependent manner. However, the antinociceptive effect of cannabidiol was significantly higher in the late phase of the formalin test than that in the early phase. Therefore, a non-psychoactive cannabinoid, cannabidiol may be developed as therapeutic agents in conditions, such as persistent inflammatory pain for which primary treatments are insufficient or not possible.