Study on Efficacy and Mechanism of Herbal Medicine in Neuropathic Pain

中草药治疗神经性疼痛的功效及机制研究

• 批准号: 15591618
• 负责人: ARITA Hideko
• 金额: $ 2.11万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591618/
• 关键词: Herbal Medicine; Sokei-Kakketsu-to; Processed Aconiti Tuber; Mesaconitine; Lactoferrin; Morphine Tolerance; U50488H; MK-801; ラットCCIモデル; 坐骨神経部分損傷モデル; 修治ブシ末; 熱刺激; 圧刺激; 桂枝加朮附湯; 真武湯; 修治附子末

1. Previous studies with the rat chronic constriction injury (CCI) model have shown that Sokei-kakketsu-to suppressed increased hypersensitivity to mechanical or heat stimuli ; and its mechanism of action is via noradrenergic activation of the descending inhibitory system. On the other hand, in similar studies on Keishi-ka-jutsubu-to and Shinbu-to, no suppression of increased hypersensitivity was observed.2. Processed Aconiti tuber, a Chinese herbal medicine, suppressed increased hypersensitivity to heat or pressure stimuli dose-dependently in a rat CCI model, and it was suggested that part of the mechanism of action was via kappa-opioid receptor. Lactoferrin, administered intrathecally or intraperitoneally, also suppressed hypersensitivity to heat or mechanical stimuli, dose-dependently, and it was suggested that the action was via mu-opioid receptor. Moreover, combined administration of processed Aconiti tuber and lactoferrin, both at sub-analgesic doses, showed a hypersensitivity su … More ppressing effect, suggesting lactoferrin may enhance the hypersensitivity suppressing effect of processed Aconiti tuber.3. The suppressing effect of processed Aconiti tuber on morphine tolerance was investigated using mice. Sub-analgesic doses of processed Aconiti tuber dose-dependently suppressed the morphine tolerance induced by cyclic administration of morphine (once a day for seven days). It was indicated that this action was mainly due to mesaconitine, a constitutive alkaloid. Even after morphine tolerance had developed, processed Aconiti tuber was shown to reverse the tolerance. Those morphine tolerance suppressing actions of processed Aconiti tuber have been proved to be via kappa-opioid receptor. Then, morphine tolerance suppressing effects were investigated regarding U50488H, a selective kappa-opioid receptor agonist, and MK-801, an NMDA receptor antagonist. U50488H inhibited development of morphine tolerance, and it also had a tolerance-reversing action on established tolerance. On the other hand, although MK-801 suppressed the development of morphine tolerance, it failed to abolish morphine tolerance that had already been established. Less

1.以往的研究与大鼠慢性压迫性损伤（CCI）模型表明，Sokei-kakketsu-to抑制增加过敏性机械或热刺激;其作用机制是通过去甲肾上腺素能激活下行抑制系统。另一方面，在对Keishi-ka-jutsubu-to和Shinbu-to的类似研究中，没有发现对超敏反应增加的抑制作用。炮制麦冬能剂量依赖性地抑制大鼠CCI模型对热或压力刺激的超敏反应，其部分作用机制可能是通过κ-阿片受体。鞘内或腹腔内给药的乳铁蛋白也抑制对热或机械刺激的超敏反应，呈剂量依赖性，并表明该作用是通过μ-阿片受体。此外，在亚镇痛剂量下，加工块茎和乳铁蛋白的联合给药显示出超敏反应， ...更多信息 抑制作用，提示乳铁蛋白可能增强了加工山药的抗过敏作用.以小鼠为实验对象，研究了炮制麦冬对吗啡耐受的抑制作用。亚镇痛剂量的炮制麦冬剂量依赖性地抑制吗啡周期性给药（每天一次，连续7天）诱导的吗啡耐受。结果表明，该作用主要是由于新乌头碱，一个组成生物碱。即使在吗啡耐受性已经形成之后，加工过的块茎也被证明可以逆转耐受性。已证实炮制麦冬抑制吗啡耐受的作用是通过κ-阿片受体实现的。然后，关于选择性κ-阿片样物质受体激动剂U 50488 H和NMDA受体拮抗剂MK-801，研究了吗啡耐受抑制作用。U 50488 H抑制吗啡耐受的形成，并对已建立的耐受具有逆转作用。另一方面，虽然MK-801抑制了吗啡耐受的发展，但它未能消除已经建立的吗啡耐受。少

项目成果

Inhibition of morphine tolerance by processed Aconiti tuber is mediated through activation of kappa opioid receptors.

加工过的附子块茎对吗啡耐受的抑制作用是通过激活κ阿片受体来介导的。

• 发表时间: 2006
• 期刊: Journal of Ethnopharmacology (Epub ahead of print)
• 作者: Tanaka K;Morioka H;et al.;Michihisa Zemmyo et al.;Michihisa Zemmyo;Xu H 他;Shu H 他;Shu H 他
• 通讯作者: Shu H 他

The Analgesic Effect of Lactferrin in a Rat of Neuropathic Pain

乳铁蛋白对神经性疼痛大鼠的镇痛作用

• 发表时间: 2004
• 期刊: 11th International Pain Clinic World Society of Pain Clinicians
• 作者: Hideko Arita;et al.
• 通讯作者: et al.

Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine

• DOI: 10.1016/j.jep.2005.08.017
• 发表时间: 2006-02-20
• 期刊: JOURNAL OF ETHNOPHARMACOLOGY
• 影响因子: 5.4
• 作者: Shu, HH;Arita, H;Hanaoka, K
• 通讯作者: Hanaoka, K

神経因性疼痛に対し鎮痛効果を示す新規組成物

对神经性疼痛具有镇痛作用的新型组合物

• 发表时间: 2004

Hideko Arita: "The analgesic effect of processed aconit tuber in CCI rat."11^<th> International Pain clinic(11〜17, July, 2004), World Society of Pain Clinicians (WSPC)(学会発表). (2004)

Hideko Arita：“加工乌头块茎对 CCI 大鼠的镇痛作用”。第 11 届国际疼痛诊所（2004 年 7 月 11-17 日），世界疼痛临床医师协会（WSPC）（2004 年）。