Cannabidiol reverses mechanical hypersensitivity in a mouse model of apical periodontitis

Cannabidiol (CBD) has both analgesic and anti-inflammatory properties. Because CBD is not psychotomimetic, it could be an excellent nonopioid alternative for various pain disorders. The aim was to assess the effectiveness of CBD as an analgesic for apical periodontitis-induced mechanical hypersensitivity (MH), its site of action (peripheral or central), and the potential involvement of transient receptor potential vanilloid 1 (TRPV1), using a mouse behavioral model of apical periodontitis (AP). Male and female mice underwent pulp exposure of the left maxillary first molar (AP group) or sham surgery (Sham group). Mechanical hypersensitivity was assessed 21 days after surgery using von Frey filaments on the left vibrissal pad. Apical periodontitis mice that received a single dose of oral CBD (AP [CBD]) experienced a significant reduction in MH at 45 minutes and 120 minutes compared with AP mice that received vehicle (AP [Veh]). The analgesic effect in males was significantly greater than in females at this CBD dose. Intrathecal and intracisternal (IC), but not ipsilateral intraoral, CBD injections reduced MH in the male AP (CBD) group, indicating a central site of action of CBD in this model of odontogenic pain. Furthermore, intraperitoneal and IC injection of AMG 517 (TRPV1 antagonist) before an oral CBD dose blocked the CBD analgesic effect in male mice, suggesting TRPV1's involvement. Overall, this study shows, for the first time, that oral CBD can be an effective analgesic for apical periodontitis-induced MH. This analgesic effect was mediated through a central site of action and involved the TRPV1 channel.