State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences, 100050, China.
Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.
Eur J Pharmacol. 2019 Jul 5;854:101-108. doi: 10.1016/j.ejphar.2019.03.061. Epub 2019 Apr 4.
Management of chronic pain is restricted by the lack of effective tools. This study evaluated the efficacies of sinomenine combined gabapentin or ligustrazine hydrochloride in treating peripheral and central chronic neuropathic pain. The study was conducted in mice with photochemically induced sciatic nerve injury, and in rats with photochemically induced spinal cord injury. For assessing the effectiveness of combined therapy, sinomenine, gabapentin or ligustrazine hydrochloride was injected intraperitoneally (i.p.), and pain behavioral tests were performed. At sub-effective dosages, pre-administration of sinomenine (for 60 min) plus gabapentin or ligustrazine hydrochloride, generated significant anti-allodynic effects in mice or rats with peripheral or central neuropathic pain. However, these effects were abolished when gabapentin or ligustrazine hydrochloride was pre-administered, and then sinomenine was given 60 min later. The combined efficacies of sinomenine and gabapentin or ligustrazine hydrochloride, cannot be blocked or reversed by the naloxone, suggesting the underlying mechanism is not mediated by opioid receptors. Moreover, following repeated treatments, sinomenine and gabapentin combination increased the baseline mechanical threshold, while generating prolonged analgesia, without introducing notable side effects. Sinomenine can enhance the efficacy of gabapentin or ligustrazine hydrochloride in rodent models of peripheral or central neuropathic pain, without introducing tolerance or other notable side effects. Findings of current study suggest that combing sinomenine and gabapentin or ligustrazine hydrochloride could be highly beneficial in neuropathic pain therapies.
慢性疼痛的管理受到缺乏有效工具的限制。本研究评估了盐酸青藤碱联合加巴喷丁或盐酸川芎嗪治疗周围和中枢性慢性神经病理性疼痛的疗效。该研究在光化学诱导坐骨神经损伤的小鼠和光化学诱导脊髓损伤的大鼠中进行。为了评估联合治疗的效果，将盐酸青藤碱、加巴喷丁或盐酸川芎嗪腹腔内注射（i.p.），并进行疼痛行为测试。在亚有效剂量下，盐酸青藤碱（60 分钟前）联合加巴喷丁或盐酸川芎嗪预处理，在有周围或中枢神经病理性疼痛的小鼠或大鼠中产生显著的抗痛觉过敏作用。然而，当加巴喷丁或盐酸川芎嗪预先给药，然后 60 分钟后给予盐酸青藤碱时，这些作用被消除。盐酸青藤碱和加巴喷丁或盐酸川芎嗪的联合疗效不能被纳洛酮阻断或逆转，表明其潜在机制不是通过阿片受体介导的。此外，经过重复治疗后，盐酸青藤碱和加巴喷丁联合使用增加了机械基础阈值，同时产生了延长的镇痛作用，没有引入明显的副作用。盐酸青藤碱可以增强加巴喷丁或盐酸川芎嗪在周围或中枢性神经病理性疼痛模型中对啮齿动物的疗效，而不会产生耐受性或其他明显的副作用。本研究的结果表明，联合使用盐酸青藤碱和加巴喷丁或盐酸川芎嗪可能对神经病理性疼痛的治疗非常有益。
