Sepulveda Diana E, Morris Daniel P, Raup-Konsavage Wesley M, Sun Dongxiao, Vrana Kent E, Graziane Nicholas M
Department of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
Eur J Pain. 2022 Oct;26(9):1950-1966. doi: 10.1002/ejp.2016. Epub 2022 Aug 4.
Cannabigerol (CBG) is a non-psychoactive phytocannabinoid produced by the plant Cannabis sativa with affinity to various receptors involved in nociception. As a result, CBG is marketed as an over-the-counter treatment for many forms of pain. However, there is very little research-based evidence for the efficacy of CBG as an anti-nociceptive agent.
To begin to fill this knowledge gap, we assessed the anti-nociceptive effects of CBG in C57BL/6 mice using three different models of pain; cisplatin-induced peripheral neuropathy, the formalin test, and the tail-flick assay.
Using the von Frey test, we found that CBG-attenuated mechanical hypersensitivity evoked by cisplatin-induced peripheral neuropathy in both male and female mice. Additionally, we observed that this CBG-induced reduction in mechanical hypersensitivity was attenuated by the α -adrenergic receptor antagonist atipamezole (3 mg/kg, i.p.) and the CB R antagonist, AM4113 (3 mg/kg, i.p.), and blocked by the CB R antagonist/inverse agonist, SR144528 (10 mg/kg, i.p.). We found that the TRPV1 antagonist, SB705498 (20 mg/kg, i.p.) was unable to prevent CBG actions. Furthermore, we show that CBG:CBD oil (10 mg/kg, i.p.) was more effective than pure CBG (10 mg/kg) at reducing mechanical hypersensitivity in neuropathic mice. Lastly, we show that pure CBG and CBG:CBD oil were ineffective at reducing nociception in other models of pain, including the formalin and tail flick assays.
Our findings support the role of CBG in alleviating mechanical hypersensitivity evoked by cisplatin-induced peripheral neuropathy, but highlight that these effects may be limited to specific types of pain.
There are few effective treatments for neuropathic pain and neuropathic pain is projected to increase with the aging population. We demonstrate that CBG (cannabigerol) and CBG:CBD oil attenuate neuropathy-induced mechanical hypersensitivity mice. Second, we identify receptor targets that mediate CBG-induced reduction in mechanical hypersensitivity in neuropathic mice. Third, we demonstrate that an acute injection of CBG is anti-nociceptive specifically for neuropathic pain rather than other forms of pain, including persistent pain and thermal pain.
大麻二酚（CBG）是一种由大麻植物产生的非精神活性植物大麻素，对参与痛觉感受的多种受体具有亲和力。因此，CBG作为多种疼痛形式的非处方治疗药物上市销售。然而，关于CBG作为一种抗伤害感受剂的疗效，基于研究的证据非常少。
为了开始填补这一知识空白，我们使用三种不同的疼痛模型评估了CBG对C57BL/6小鼠的抗伤害感受作用；顺铂诱导的周围神经病变、福尔马林试验和甩尾试验。
使用von Frey试验，我们发现CBG减轻了顺铂诱导的周围神经病变在雄性和雌性小鼠中引起的机械性超敏反应。此外，我们观察到，α-肾上腺素能受体拮抗剂阿替美唑（3毫克/千克，腹腔注射）和CB1R拮抗剂AM4113（3毫克/千克，腹腔注射）减弱了CBG诱导的机械性超敏反应的降低，而CB1R拮抗剂/反向激动剂SR144528（10毫克/千克，腹腔注射）则阻断了这种降低。我们发现，TRPV1拮抗剂SB705498（20毫克/千克，腹腔注射）无法阻止CBG的作用。此外，我们表明，CBG:CBD油（10毫克/千克，腹腔注射）在减轻神经病变小鼠的机械性超敏反应方面比纯CBG（10毫克/千克）更有效。最后，我们表明，纯CBG和CBG:CBD油在减轻其他疼痛模型（包括福尔马林试验和甩尾试验）中的伤害感受方面无效。
我们的研究结果支持CBG在减轻顺铂诱导的周围神经病变引起的机械性超敏反应中的作用，但强调这些作用可能仅限于特定类型的疼痛。
神经性疼痛的有效治疗方法很少，而且随着人口老龄化，神经性疼痛预计会增加。我们证明了CBG（大麻二酚）和CBG:CBD油减轻了神经病变诱导的小鼠机械性超敏反应。其次，我们确定了介导CBG诱导的神经病变小鼠机械性超敏反应降低的受体靶点。第三，我们证明了急性注射CBG对神经性疼痛具有抗伤害感受作用，而不是对其他形式的疼痛，包括持续性疼痛和热痛。
