Lee Jeong-Yun, Yoon Seo-Yeon, Won Jonghwa, Kim Han-Byul, Kang Youngnam, Oh Seog Bae
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea; Dental Research Institute and Department of Neurobiology & Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Neuroscience. 2017 Sep 1;358:28-36. doi: 10.1016/j.neuroscience.2017.06.024. Epub 2017 Jun 27.
Sinomenium acutum has been used in traditional medicine to treat a painful disease such as rheumatic arthritis and neuralgia. Sinomenine, which is a main bioactive ingredient in Sinomenium acutum, has been reported to have an analgesic effect in diverse pain animal models. However little is known about the detailed mechanisms underlying peripheral analgesic effect of sinomenine. In the present study, we aimed to elucidate its cellular mechanism by using formalin-induced acute inflammatory pain model in mice. We found that intraperitoneal (i.p.) administration of sinomenine (50mg/kg) suppressed formalin-induced paw licking behavior in both the first and the second phase. Formalin-induced c-Fos protein expression was also suppressed by sinomenine (50mg/kg i.p.) in the superficial dorsal horn of spinal cord. Whole-cell patch-clamp recordings from small-sized dorsal root ganglion (DRG) neurons revealed that sinomenine reversibly increased the spike threshold and the threshold current intensity for evoking a single spike and decreased firing frequency of action potentials evoked in response to a long current pulse. Voltage-gated sodium currents (I) were also significantly reduced by sinomenine in a dose-dependent manner (IC=2.3±0.2mM). Finally, we confirmed that intraplantar application of sinomenine suppressed formalin-induced pain behavior only in the first phase, but not the second phase. Taken together, our results suggest that sinomenine has a peripheral analgesic effect by inhibiting I.
青风藤已被用于传统医学治疗诸如风湿性关节炎和神经痛等疼痛性疾病。青藤碱是青风藤中的主要生物活性成分，据报道在多种疼痛动物模型中具有镇痛作用。然而，关于青藤碱外周镇痛作用的详细机制知之甚少。在本研究中，我们旨在通过使用福尔马林诱导的小鼠急性炎症性疼痛模型来阐明其细胞机制。我们发现腹腔注射（i.p.）青藤碱（50mg/kg）可抑制福尔马林诱导的第一和第二阶段的舔足行为。福尔马林诱导的c-Fos蛋白表达在脊髓背角浅层也被青藤碱（50mg/kg i.p.）抑制。对小型背根神经节（DRG）神经元进行的全细胞膜片钳记录显示，青藤碱可逆地提高了引发单个动作电位的阈电位和阈电流强度，并降低了对长电流脉冲诱发的动作电位的发放频率。青藤碱还以剂量依赖性方式显著降低电压门控钠电流（I）（IC = 2.3±0.2mM）。最后，我们证实足底注射青藤碱仅在第一阶段而非第二阶段抑制福尔马林诱导的疼痛行为。综上所述，我们的结果表明青藤碱通过抑制I具有外周镇痛作用。
