Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats.
Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats.
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DOI：
10.1155/2015/293423
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发表时间：
2015
影响因子：
3.1
通讯作者：
Kim HK
中科院分区：
文献类型：
--
作者：
Kim HY;Lee I;Chun SW;Kim HK
我们之前的研究表明活性氧（ROS）清除剂通过脊柱机制对大鼠神经性疼痛具有镇痛作用。研究表明，脊髓超氧化物是引起持续性疼痛的重要介质之一。为了验证超氧化物衍生中间体增加导致中枢致敏和疼痛的假设，研究了鞘内注射化学ROS供体释放OH∙、OCl−或H2O2对疼痛行为的影响。t-BOOH （OH∙供体）处理后，采用全细胞膜片夹持记录法观察正常大鼠背角神经元对机械刺激的反应及胶质质（SG）神经元兴奋性的变化。鞘内给予t-BOOH或NaOCl （OCl -供体），但不给予H2O2，可显著降低后爪的机械阈值。局部应用t-BOOH后，宽动态范围神经元对机械刺激的反应增强。t-BOOH增加了SG神经元兴奋性突触后电位、去极化膜电位的频率和幅值，增加了去极化电流脉冲诱发的动作电位的频率。这些结果表明，在正常大鼠脊髓中，升高的ROS，特别是OH∙使背角神经元致敏并产生痛觉过敏。
Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either OH∙, OCl−, or H2O2 were examined on pain behaviors. Following treatment with t-BOOH (OH∙ donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl (OCl− donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially OH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats.