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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >The role of c-AMP-dependent protein kinase in spinal cord and post synaptic dorsal column neurons in a rat model of visceral pain.
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The role of c-AMP-dependent protein kinase in spinal cord and post synaptic dorsal column neurons in a rat model of visceral pain.

机译：c-AMP依赖性蛋白激酶在大鼠内脏痛模型中在脊髓和突触后背柱神经元中的作用。

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摘要

Visceral noxious stimulation induces central neuronal plasticity changes and suggests that the c-AMP-dependent protein kinase (PKA) signal transduction cascade contributes to long-term changes in nociceptive processing at the spinal cord level. Our previous studies reported the clinical neurosurgical interruption of post synaptic dorsal column neuron (PSDC) pathway by performing midline myelotomy effectively alleviating the intractable visceral pain in patients with severe pain. However, the intracellular cascade in PSDC neurons mediated by PKA nociceptive neurotransmission was not known. In this study, by using multiple experimental approaches, we investigated the role of PKA in nociceptive signaling in the spinal cord and PSDC neurons in a visceral pain model in rats with the intracolonic injection of mustard oil. We found that mustard oil injection elicited visceral pain that significantly changed exploratory behavior activity in rats in terms of decreased numbers of entries, traveled distance, active and rearing time, rearing activity and increased resting time when compared to that of rats receiving mineral oil injection. However, the intrathecal infusion of PKA inhibitor, H89 partially reversed the visceral pain-induced effects. Results from Western blot studies showed that mustard oil injection significantly induced the expression of PKA protein in the lumbosacral spinal cord. Immunofluorescent staining in pre-labeled PSDC neurons showed that mustard oil injection greatly induces the neuronal profile numbers. We also found that the intrathecal infusion of a PKA inhibitor, H89 significantly blocked the visceral pain-induced phosphorylation of c-AMP-responsive element binding (CREB) protein in spinal cord in rats. The results of our study suggest that the PKA signal transduction cascade may contribute to visceral nociceptive changes in spinal PSDC pathways.
机译：内脏有害刺激诱导中枢神经元可塑性变化，并表明c-AMP依赖性蛋白激酶（PKA）信号转导级联有助于脊髓水平上伤害感受过程的长期变化。我们以前的研究报告了通过执行中线肌切开术有效减轻严重疼痛患者的顽固性内脏痛，从而突触后突触背柱神经元（PSDC）通路的临床神经外科手术中断。然而，由PKA伤害性神经传递介导的PSDC神经元的细胞内级联是未知的。在这项研究中，通过使用多种实验方法，我们调查了结肠内注射芥子油的大鼠内脏痛模型中PKA在脊髓和PSDC神经元的伤害性信号传导中的作用。我们发现，与接受矿物油注射的大鼠相比，芥末油注射引起的内脏疼痛显着改变了大鼠的探索行为活动，其减少了进入次数，行进距离，活跃和抚养时间，抚养活动和休息时间。然而，鞘内注射PKA抑制剂H89可以部分逆转内脏痛引起的作用。 Western印迹研究的结果表明，注入芥子油可显着诱导腰s脊髓中PKA蛋白的表达。预先标记的PSDC神经元的免疫荧光染色表明，芥末油注射极大地诱导了神经元的分布。我们还发现鞘内注射PKA抑制剂H89可以显着阻断大鼠内脏痛诱导的脊髓c-AMP响应元件结合（CREB）蛋白的磷酸化。我们的研究结果表明，PKA信号转导级联可能有助于脊髓PSDC途径的内脏伤害感受变化。

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