Efficacy and mechanism of the antinociceptive effects of cannabidiol on acute orofacial nociception induced by Complete Freund's Adjuvant in male Mus musculus mice

Objectives: The objectives were to investigate the efficacy and mechanisms of cannabidiol on orofacial noci-ception induced by Complete Freund's Adjuvant (CFA) in male Mus musculus mice. Design: For the study of efficacy, mice were divided into seven groups: sham; inflammation; and cannabidiol 0.5, 1, 3, 5, and 10 mg. For the study of mechanisms of cannabidiol, mice were divided into six groups: sham, inflammation, calcitonin gene-related peptide (CGRP) antagonist with and without cannabidiol, and vanilloid receptor 1 antagonist with and without cannabidiol. Spontaneous pain-like behaviors, trigeminal nociception, and trigeminal modulating activity were investigated.Results: CFA injected in the right masseter muscle significantly induced spontaneous pain-like behaviors and the trigeminal nociceptive pathway. This effect was inhibited by injection of 1, 3, 5, and 10 mg of cannabidiol. The 50 % inhibitory concentration of cannabidiol on antinociception was found to be 3 mg/kg. In addition, there was no difference in spontaneous pain-like behaviors with vanilloid receptor 1 antagonist injected before treatment with cannabidiol compared to saline control. Reduced c-fos expression was observed in the trigeminal nucleus caudalis and periaqueductal gray in the group injected with CGRP antagonist before treatment with cannabidiol.Conclusion: The antinociceptive effects of cannabidiol induced by acute orofacial nociception is mediated by vanilloid receptor 1 but not by CGRP. Cannabidiol can act with peripheral nonpeptidergic neurons and can be used as an alternative drug or as a synergistic medication in pain treatment.

Automated summary

The study aimed to investigate the efficacy and mechanisms of cannabidiol on orofacial nociception induced by CFA in male Mus musculus mice. Cannabidiol was found to inhibit pain-like behaviors and trigeminal nociceptive pathway induced by CFA injection, with a 50% inhibitory concentration of 3 mg/kg. Cannabidiol's antinociceptive effects were mediated by vanilloid receptor 1 but not by CGRP, suggesting its potential use in pain treatment.