Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.
Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.
复制标题
吴茱萸碱通过瞬时受体电位 V1 通道的激活和随后的脱敏来抑制辣椒素诱导的热痛觉过敏。
DOI：
10.1007/s11418-015-0929-1
复制
发表时间：
2016-01
影响因子：
3.3
通讯作者：
Dai Y
中科院分区：
文献类型：
--
作者：
Iwaoka E;Wang S;Matsuyoshi N;Kogure Y;Aoki S;Yamamoto S;Noguchi K;Dai Y
吴茱萸（Evodiae fructus，EF）为吴茱萸（Evodia rutaecarpa Bentham）的果实，长期以来在中药和日药中用作镇痛药。然而，其药理作用的潜在分子机制尚不清楚。在这里，我们利用钙成像、全细胞膜片钳记录和行为分析，研究了 EF 及其主要化合物吴茱萸碱对瞬时受体电位 (TRP) V1 通道的药理作用。背根神经节 (DRG) 神经元和 TRPV1 或 TRPA1 转染的人胚胎肾源 (HEK) 293 细胞用于钙成像或全细胞膜片钳记录。二十只雄性成年斯普拉格-道利大鼠用于辣椒素诱导的热痛觉过敏行为分析。我们发现吴茱萸碱可诱导分离的大鼠 DRG 神经元亚群中细胞内钙的显着增加和强劲的内向电流，其中大多数神经元也对辣椒素敏感。吴茱萸碱的作用被 TRPV1 的竞争性拮抗剂辣椒西平完全阻断。吴茱萸碱在TRPV1转染的HEK293细胞中诱导显着的内向电流，但在TRPA1转染的HEK293细胞中不诱导显着的内向电流。吴茱萸碱预处理显着降低了辣椒素诱导的电流。此外，吴茱萸碱的体内预处理可抑制大鼠足底注射辣椒素引起的热痛觉过敏。这些结果表明，EF 和吴茱萸碱的镇痛作用可能是由于感觉神经元中 TRPV1 的激活和随后的脱敏所致。
Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons.