Cannabidiol Decreases Neuropathic Pain in Mice by Release of Opioid Peptides

Abstract

Background: More than 100 phytocannabinoids have already been identified present in varying percentages of composition in the various plants of the genus Cannabis, including cannabidiol (CBD). Some evidences have demonstrated the effectiveness of CBD in treating neuropathic pain. We evaluated the participation of the opioid system in peripheral antinociception induced by the administration of CBD in the face of neuropathic pain induced by constriction of the sciatic nerve. Methods: Neuropathic pain was induced with the constriction of the sciatic nerve while the nociceptive threshold was measured using the pressure test of the mice paw. All drugs were administered by intraplantar injections in the right hind paw of mice. Results: Bestatin, an inhibitor of the enzyme aminopeptidase N, which degrades opioid peptides, potentiated the antinociceptive effect of the lowest administered dose of CBD (5 μg/paw). The antinociceptive effect of CBD was reversed by the administration of naloxone, a non-selective antagonist for opioid receptor. The selective antagonist for μ opioid receptor, clocinnamox, reversed the antinociceptive effect of CBD. Naltrindole, a selective antagonist for δ opioid receptors, and nor-binaltorphymine, a selective antagonist for κ opioid receptors, partially reversed the antinociception induced by CBD. Conclusions: Our data suggest the participation of the opioid system in CBD-induced peripheral antinociception in the model of neuropathic pain induced by sciatic nerve constriction in mice. Keywords: Cannabidiol; Neuropathic Pain; Peripheral Antinociception; Opioid System