Modern pain management guidelines advocate for a multimodal approach, and sociocultural changes have revived interest in cannabinoid use, especially cannabidiol (CBD), for pain relief.
The tricyclic antidepressant amitriptyline (AT) is approved for pain-related syndromes, both as a standalone treatment and within a multimodal approach. This study explores the sex- and dose-dependent effects of CBD and AT antinociception in the 2.5% formalin inflammatory pain model.
Inflammatory pain, characterized by tissue hypersensitization, is a significant component of rheumatic diseases and often results in chronic pain.
Male and female C57BL/6J mice were pretreated with vehicle, CBD (0.3-100 mg/kg), or AT (0.1-30 mg/kg) before formalin testing in the 2.5% formalin inflammatory pain model. The acute and inflammatory phases were assessed, and the calculated median effective doses of CBD and AT were combined to explore potential additive effects.
According to the study, CBD induced antinociception at 30-100 mg/kg in males and 100 mg/kg in females. In the inflammatory phase, CBD exhibited antinociceptive effects at doses of 2.5-100 mg/kg in males and 10-100 mg/kg in females. AT induced antinociception at 10 mg/kg for all mice in the acute phase and at 0.3 mg/kg in males and 3 mg/kg in females in the inflammatory phase. The combination of CBD and AT produced additive effects in the acute phase for all mice and in the inflammatory phase for males.
“The study suggests that the combination of CBD and AT enhances antinociceptive effects in inflammatory pain, with serotonin and sex playing a role in mediating these effects. The findings support the utilization of CBD within a multimodal approach to pain management, especially for inflammatory pain”, study concluded.