Changes in expression of voltage-dependent ion channel subunits in dorsal root ganglia of rats with radicular injury and pain
Changes in expression of voltage-dependent ion channel subunits in dorsal root ganglia of rats with radicular injury and pain
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DOI：
10.1097/00007632-200207150-00007
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发表时间：
2002-07-15
期刊：
影响因子：
3
通讯作者：
Tanabe, T
中科院分区：
文献类型：
--
作者：
Abe, M;Kurihara, T;Tanabe, T
研究设计.电压依赖性离子通道亚单位的表达的变化进行了检查，在神经根痛状态。此外，加巴喷丁对神经根性疼痛的抗伤害性作用与对周围神经性疼痛的作用进行了比较。阐明神经根性疼痛发生的分子机制，并探讨神经根性疼痛对gabapentin的反应性。背景资料概要：周围神经损伤可诱导背根神经节神经元电压依赖性Na+和Ca 2+通道亚单位表达的动态变化。然而，在神经根性疼痛状态下Na+和Ca 2+通道亚基的表达谱尚未被检测。制备两种神经根性疼痛模型和一种周围神经病理性疼痛模型。采用半定量逆转录-聚合酶链反应（RT-PCR）技术，观察了痛模型大鼠背根神经节Na+和Ca ~（2+）通道亚单位的表达水平。加巴喷丁的抗伤害性作用在行为学研究中使用上述疼痛模型进行了检查。所有三种神经病理性疼痛手术引起的机械异常性疼痛和热痛觉过敏。仅在周围神经损伤模型中观察到Na（v）1.3 Na+通道和Ca（v）α（2）δ Ca 2+通道亚单位的上调。在所有三种疼痛模型大鼠中观察到Na（v）1.9通道的下调。较低剂量的加巴喷丁在缓解神经根痛大鼠的机械性痛觉超敏反应方面更有效。在所有三种模型中发现的Nav1.9的减少可能与神经病理性疼痛状态有关，包括神经根性疼痛。周围神经病理性疼痛大鼠对加巴喷丁的敏感性较低，部分原因可能是背根神经节中Ca（v）α（2）δ的显著上调，这表明加巴喷丁可能对神经根性疼痛治疗更有效。
Study Design. Changes in expression of voltage-dependent ion channel subunits were examined in the radicular pain state. Furthermore, antinociceptive effects of gabapentin on radicular pain were compared with effects on peripheral neuropathic pain.Objectives. To clarify molecular substrates involved in the development of radicular pain, and to investigate the responsiveness of radicular pain to gabapentin.Summary of Background Data: Peripheral nerve inuries are known to induce dynamic changes of voltage-dependent Na+ and Ca2+ channel subunits expression in dorsal root ganglion neurons. However, the expression profiles of Na+ and Ca2+ channel subunits in the radicular pain state have not been examined.Methods. Two radicular pain models and one periheral neuropathic pain model were prepared. By using semiquantitative reverse transcriptase-polymerase chain reaction, the expression levels of several Na+ and Ca2+ channel subunits in the dorsal root ganglions of these pain model rats were investigated. The antinociceptive effects of gabapentin were examined in a behavioral study using the aforementioned pain models.Results. All three neuropathic pain operations induced comparable mechanical allodynia and thermal hyperalgesia. The upregulation of the Na(v)1.3 Na+ channel and Ca(v)alpha(2)delta Ca2+ channel subunits was observed only in the peripheral nerve injury model. A downregulation of the Na(v)1.9 channel was observed in all three pain model rats. A lower dose of gabapentin was significantly more effective in alleviating the mechanical allodynia of rats with radicular pain.Conclusions. The reduction of Nav1.9 found in allthree models may link to the neuropathic pain state, including radicular pain. The lower sensitivity to gabapentin in rats with peripheral neuropathic pain might be partly explained by the marked upregulation of Ca(v)alpha(2)delta in the dorsal root ganglions, suggesting that gabapentin may be more effective in radicular pain treatment.