Anti-allodynic effect of the flavonoid myricetin in a rat model of neuropathic pain: Involvement of p38 and protein kinase C mediated modulation of Ca2+ channels
Anti-allodynic effect of the flavonoid myricetin in a rat model of neuropathic pain: Involvement of p38 and protein kinase C mediated modulation of Ca2+ channels
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DOI：
10.1016/j.ejpain.2010.04.005
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发表时间：
2010-11-01
影响因子：
3.6
通讯作者：
Schaefers, Maria
中科院分区：
文献类型：
--
作者：
Hagenacker, Tim;Hillebrand, Imke;Schaefers, Maria
黄酮类化合物作为化疗剂和抗炎剂越来越多地被人群摄入。杨梅素是一种天然存在的黄酮类化合物，以其抗肿瘤和抗炎作用而闻名。最近，行为学研究表明，在疼痛的动物模型中具有潜在的镇痛作用。初步研究表明，黄酮类化合物诱导的细胞内蛋白激酶的调制和电压激活的钙通道的相互作用，本研究的目的是研究在神经病理性疼痛模型（脊神经结扎，SNL）大鼠的杨梅苷的镇痛作用。为了确定潜在的作用机制，进行离体大鼠背根神经节（DRG）神经元的体外全细胞膜片钳记录以分析电压激活的钙通道电流（I-Ca（V））的调节和细胞内激酶磷酸化如p38丝裂原活化蛋白激酶（p38）或蛋白激酶C（PKC）的影响。单次注射杨梅素（0.1-10 mg/kg i. p.）减少持续数小时的SNL诱导的机械异常性疼痛和热痛觉过敏。在体外，低浓度（0.1-5 μ M）的杨梅素使I-Ca（V）（去极化从-80至0 mV）降低（10-56%）。阻断PKC（20 μ M白屈菜红碱30分钟），但不阻断p38（10 μ M SB 203580 30分钟），这种降低被消除。相反，较高浓度（10-100 μ M）的杨梅素诱导的I-Ca（V）的增加（20-40%），这是由抑制p38，但不是PKC的阻断。我们得出结论，杨梅素短暂减少建立神经性疼痛行为。其镇痛作用可能与PKC诱导DRG神经元I-Ca（V）减少有关。(C)2010年，国际疼痛分会研究协会欧洲联合会。由爱思唯尔有限公司出版。保留所有权利。
Flavonoids are increasingly ingested by the population as chemotherapeutic and anti-inflammatory agents. Myricetin is a naturally occurring flavonoid known for its anti-neoplastic and anti-inflammatory effects. Recently, behavioral studies indicate a potential analgesic effect in animal models of pain. Pilot studies suggest a flavonoid-induced modulation of intracellular protein kinases and interactions with voltage activated calcium channels.The aim of this study was to investigate the analgesic effect of myricetin in a neuropathic pain model (spinal nerve ligation, SNL) in rats. To identify potential mechanisms of action, in vitro whole cell patch-clamp recordings of isolated rat dorsal root ganglia (DRG) neurons were performed to analyze the modulation of voltage activated calcium channel currents (I-Ca(V)) and the influence of intracellular kinase phosphorylation such as p38 mitogen-activated protein kinase (p38) or protein kinase C (PKC).In vivo, a single injection of myricetin (0.1-10 mg/kg i.p.) reduced SNL-induced mechanical allodynia and thermal hyperalgesia lasting for several hours. In vitro, I-Ca(V) (depolarization from -80 to 0 mV) were reduced (10-56%) by low (0.1-5 mu M) concentrations of myricetin. This decrease was abolished by blockade of PKC (20 mu M chelerythrine for 30 min), but not of p38 (10 mu M SB203580 for 30 min). In contrast, higher (10-100 mu M) concentrations of myricetin induced an increase of I-Ca(V) (20-40%), which was blocked by inhibition of p38, but not of PKC.We conclude that myricetin transiently reduces established neuropathic pain behavior. This analgesic effect may be related to its PKC-induced decrease of I-Ca(V) in DRG neurons. (C) 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.