N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice.
N-Demethylsinomenine, an active metabolite of sinomenine, attenuates chronic neuropathic and inflammatory pain in mice.
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DOI：
10.1038/s41598-021-88521-z
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发表时间：
2021-04-29
影响因子：
4.6
通讯作者：
Zhu Q
中科院分区：
文献类型：
--
作者：
Zhou Z;Qiu N;Ou Y;Wei Q;Tang W;Zheng M;Xing Y;Li JJ;Ling Y;Li J;Zhu Q
慢性疼痛是一个重要的公共卫生问题，困扰着全球近30%的人口，但目前的药物治疗是不够的。N-去甲基青藤碱是青藤碱的活性代谢产物，有抗术后疼痛的作用。本研究调查了N-去甲基青藤碱是否对慢性疼痛有效，或者重复治疗是否会改变其效果。慢性压迫性损伤（CCI）手术和完全弗氏佐剂（CFA）足底注射诱导了至少7天的显著和可靠的机械性异常性疼痛。用N-去甲基青藤碱（10-40 mg/kg，i. p.）剂量依赖性地减弱CCI诱导的神经性疼痛和CFA诱导的炎症性疼痛中的机械性异常性疼痛。N-去甲基青藤碱减轻CFA引起的机械性异常性疼痛的效力略高于青藤碱。在重复治疗期间，N-去甲青藤碱保持其对神经性疼痛和炎性疼痛的抗异常性疼痛作用，而不产生遗留效应。预先给予γ-氨基丁酸A型（GABAA）受体拮抗剂荷包牡丹碱（bicuculline）几乎完全阻断N-去甲基青藤碱（40 mg/kg）对CCI和CFA小鼠的抗痛觉超敏作用。我们的研究结果表明，N-去甲基青藤碱表现出GABAA受体介导的抗异常性疼痛的神经病理性和炎症性疼痛的小鼠模型，这表明它可能是一个有用的新的药物治疗慢性疼痛的控制。
Chronic pain is a significant public health problem that afflicts nearly 30% of the global population, but current pharmacotherapies are insufficient. Previous report indicated that N-demethylsinomenine, an active metabolite of sinomenine, is efficacious against postoperative pain. The present study investigated whether N-demethylsinomenine is effective for chronic painful conditions or whether repeated treatment alters its effect. Both chronic constriction injury (CCI) surgery and complete Freund’s adjuvant (CFA) intraplantar injection induced significant and reliable mechanical allodynia at least for 7 days. Acute treatment with N-demethylsinomenine (10–40 mg/kg, i.p.) dose-dependently attenuated the mechanical allodynia both in CCI-induced neuropathic pain and CFA-induced inflammatory pain in mice. The potency of N-demethylsinomenine for reducing CFA-induced mechanical allodynia was slightly higher than sinomenine. During the period of repeated treatment, N-demethylsinomenine maintained its anti-allodynic effect against both neuropathic and inflammatory pain without producing carry-over effect. Pretreatment with bicuculline, a selective γ-aminobutyric acid type A (GABAA) receptor antagonist, almost completely blocked the anti-allodynia of N-demethylsinomenine (40 mg/kg) both in CCI and CFA-treated mice. Our findings indicated that N-demethylsinomenine exhibits GABAA receptor-mediated anti-allodynic effects in mouse models of neuropathic and inflammatory pain, suggesting it may be a useful novel pharmacotherapy for the control of chronic pain.
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DOI：
10.12659/msm.908422
发表时间：
2018-10-26
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Liu S;Xu S;Wang Z;Guo Y;Pan W;Shen Z
通讯作者：
Shen Z
影响因子：
3.4
作者：
Li, Jun-Xu;Shah, Aparna P.;Patel, Sunny K.;Rice, Kenner C.;France, Charles P.
通讯作者：
France, Charles P.
大鼠中咪唑啉 I-2 受体激动剂 2-BFI 和阿片类药物之间的镇痛相互作用：mu-阿片类药物受体功效的作用
DOI：
10.1124/jpet.116.232421
发表时间：
2016-06-01
影响因子：
3.5
作者：
Siemian, Justin N.;Obeng, Samuel;Li, Jun-Xu
通讯作者：
Li, Jun-Xu
影响因子：
1.7
作者：
Cheng, W.-M.;Qiu, F.;Yao, X.-S.
通讯作者：
Yao, X.-S.
神经炎症驱动的慢性疼痛的新兴目标。
影响因子：
120.1
作者：
Ji, Ru-Rong;Xu, Zhen-Zhong;Gao, Yong-Jing
通讯作者：
Gao, Yong-Jing