Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.
Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.
复制标题
DOI：
10.1371/journal.pone.0039647
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hu SJ
中科院分区：
文献类型：
--
作者：
Sun W;Miao B;Wang XC;Duan JH;Ye X;Han WJ;Wang WT;Luo C;Hu SJ
疼痛性糖尿病神经病变（PDN）是糖尿病的常见并发症，对患者的生活质量产生不利影响。越来越多的证据表明 PDN 与外周伤害性初级感觉神经元的过度兴奋有关。然而，PDN 背后的精确细胞机制仍然难以捉摸。这可能导致缺乏治疗PDN的有效疗法。酚类葡萄糖苷天麻素是中草药天麻的主要成分，自古以来就被广泛用作抗惊厥、镇静、镇痛药。然而，其镇痛作用背后的细胞机制尚不清楚。本研究通过结合行为调查和电生理记录，研究了天麻素在 STZ 诱导的 PDN 实验大鼠模型中的作用，并进一步探讨了潜在的细胞机制。腹腔注射天麻素可有效减弱 STZ 注射引起的机械性异常性疼痛和热痛觉过敏。从完整背根神经节 (DRG) 的伤害性、辣椒素敏感小直径神经元获得全细胞膜片钳记录。糖尿病大鼠的记录显示，使用 GAS 可以大大消除神经元的异常过度兴奋。为了确定哪些电流参与天麻素的抗伤害作用，我们检查了天麻素对糖尿病小 DRG 神经元瞬时钠电流 (I NaT) 和钾电流的影响。糖尿病引起 I NaT 显着增强和钾电流减少，尤其是缓慢失活钾电流（I AS）； GAS 以剂量依赖性方式完全逆转了这些效应。此外，STZ 诱导的 I NaT 和总钾电流以及 I AS 电流的激活和失活动力学变化通过 GAS 标准化。这项研究为天麻素治疗慢性疼痛（包括 PDN）的外周镇痛作用提供了明确的细胞基础。
Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN.