Raup-Konsavage Wesley M, Sepulveda Diana E, Wang Jian, Dokholyan Nikolay V, Vrana Kent E, Graziane Nicholas M
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.
Department of Anesthesiology & Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA.
Biomedicines. 2023 Dec 29;12(1):83. doi: 10.3390/biomedicines12010083.
contains minor cannabinoids that have potential therapeutic value in pain management. However, detailed experimental evidence for the antinociceptive effects of many of these minor cannabinoids remains lacking. Here, we employed artificial intelligence (AI) to perform compound-protein interaction estimates with cannabichromene (CBC) and receptors involved in nociceptive signaling. Based on our findings, we investigated the antinociceptive properties of CBC in naïve or neuropathic C57BL/6 male and female mice using von Frey (mechanical allodynia), tail-flick (noxious radiant heat), formalin (acute and persistent inflammatory pain), and acetone (cold thermal) tests. For von Frey assessments, CBC dose (0-20 mg/kg, i.p.) and time (0-6 h) responses were measured in male and female neuropathic mice. For tail-flick, formalin, and acetone assays, CBC (20 mg/kg, i.p.) was administered to naïve male and female mice 1 h prior to testing. The results show that CBC (10 and 20 mg/kg, i.p.) significantly reduced mechanical allodynia in neuropathic male and female mice 1-2 h after treatment. Additionally, CBC treatment caused significant reductions in nociceptive behaviors in the tail-flick assay and in both phase 1 and phase 2 of the formalin test. Finally, we found a significant interaction in neuropathic male mice in the acetone test. In conclusion, our results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain.
含有在疼痛管理方面具有潜在治疗价值的次要大麻素。然而，许多这些次要大麻素的抗伤害感受作用的详细实验证据仍然缺乏。在这里，我们利用人工智能（AI）对大麻色烯（CBC）与伤害感受信号传导相关受体进行化合物 - 蛋白质相互作用估计。基于我们的发现，我们使用von Frey（机械性异常性疼痛）、甩尾（有害热辐射）、福尔马林（急性和持续性炎性疼痛）和丙酮（冷刺激）试验，研究了CBC在未处理或神经性C57BL/6雄性和雌性小鼠中的抗伤害感受特性。对于von Frey评估，在雄性和雌性神经性小鼠中测量CBC剂量（0 - 20 mg/kg，腹腔注射）和时间（0 - 6小时）反应。对于甩尾、福尔马林和丙酮试验，在测试前1小时给未处理的雄性和雌性小鼠腹腔注射CBC（20 mg/kg）。结果表明，CBC（10和20 mg/kg，腹腔注射）在处理后1 - 2小时显著降低了神经性雄性和雌性小鼠的机械性异常性疼痛。此外，CBC处理在甩尾试验以及福尔马林试验的第1阶段和第2阶段均导致伤害感受行为显著减少。最后，我们在丙酮试验中发现神经性雄性小鼠存在显著相互作用。总之，我们的结果表明，CBC靶向参与伤害感受信号传导的受体，并具有抗伤害感受特性，这可能使患有各种形式急性或慢性/持续性疼痛的雄性和雌性受益。
