Nerve injury increases brain-derived neurotrophic factor levels to suppress BK channel activity in primary sensory neurons.
Nerve injury increases brain-derived neurotrophic factor levels to suppress BK channel activity in primary sensory neurons.
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DOI：
10.1111/j.1471-4159.2012.07736.x
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发表时间：
2012-06
影响因子：
4.7
通讯作者：
Pan HL
中科院分区：
文献类型：
--
作者：
Cao XH;Chen SR;Li L;Pan HL
初级感觉神经元的异常过度兴奋有助于神经损伤后神经病理性疼痛的发展。神经损伤显著降低背根神经节（DRG）大电导钙激活钾通道（BK）的表达。然而，关于神经损伤如何影响DRG神经元中BK通道的活性知之甚少。在这项研究中，我们确定了在不同大小的DRG神经元的神经病理性疼痛的大鼠模型中的BK通道活性的变化和脑源性神经营养因子（BDNF）的BK通道活性降低的贡献。BK通道的活性主要存在于小型和中型DRG神经元中，并且结扎L5和L6脊神经显著降低了这些神经元中的BK电流密度。阻断BK通道显著增加假手术对照组DRG神经元的兴奋性，但在神经损伤大鼠中没有。神经损伤大鼠背根节BDNF浓度显著高于对照组。BDNF处理大大降低了对照大鼠DRG神经元的BK电流，这被抗BDNF抗体或Trk受体抑制剂K252a阻断。此外，抗BDNF抗体或K252a逆转了受损DRG神经元中BK电流的减少。BDNF处理后，DRG神经元中BKα1亚单位mRNA水平降低，抗BDNF抗体可减轻损伤后DRG神经元中BKα1 mRNA水平的降低。这些结果表明，神经损伤主要减少了BK通道的活动在小型和中型DRG神经元。BDNF水平的增加有助于神经病理性疼痛中DRG神经元中BK通道活性的降低。
Abnormal hyperexcitability of primary sensory neurons contributes to neuropathic pain development after nerve injury. Nerve injury profoundly reduces the expression of big conductance Ca2+-activated K+ (BK) channels in the dorsal root ganglion (DRG). However, little is known about how nerve injury affects BK channel activity in DRG neurons. In this study, we determined the changes in BK channel activity in different sizes of DRG neurons in a rat model of neuropathic pain and the contribution of brain-derived neurotrophic factor (BDNF) to reduced BK channel activity. The BK channel activity was present predominantly in small and medium DRG neurons, and ligation of L5 and L6 spinal nerves profoundly decreased the BK current density in these neurons. Blocking BK channels significantly increased the excitability of DRG neurons in sham control, but not in nerve-injured, rats. The BDNF concentration in the DRG was significantly greater in nerve-injured rats than in control rats. BDNF treatment largely reduced BK currents in DRG neurons in control rats, which was blocked by either anti-BDNF antibody or K252a, a Trk receptor inhibitor. Furthermore, either anti-BDNF antibody or K252a reversed reduction in BK currents in injured DRG neurons. BDNF treatment reduced the mRNA levels of BKα1 subunit in DRG neurons, and anti-BDNF antibody attenuated the reduction in the BKα1 mRNA level in injured DRG neurons. These findings suggest that nerve injury primarily diminishes the BK channel activity in small and medium DRG neurons. Increased BDNF levels contribute to reduced BK channel activity in DRG neurons in neuropathic pain.
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影响因子：
2.5
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