cannabigerol and Pain

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Asthma; Humans; Ion Channel Gating; Neurons; Pain; Peripheral Nervous System Diseases; Pulmonary Disease, Chronic Obstructive; Transient Receptor Potential Channels

Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of β-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits' skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.

Topics: Analgesics; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Hallucinogens; Mice; Pain; Rabbits

Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bony Callus; Cannabidiol; Cannabinoids; Fracture Healing; Mice; Minerals; Pain; Tibial Fractures