Plasticity and emerging role of BKCa channels in nociceptive control in neuropathic pain.
Plasticity and emerging role of BKCa channels in nociceptive control in neuropathic pain.
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DOI：
10.1111/j.1471-4159.2009.06138.x
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发表时间：
2009-07
影响因子：
4.7
通讯作者：
Pan HL
中科院分区：
文献类型：
--
作者：
Chen SR;Cai YQ;Pan HL
大电导Ca 2+激活的K+（BKCa，MaxiK）通道对调节神经元兴奋性非常重要。周围神经损伤引起初级传入神经元和脊髓背角神经元的可塑性，导致中枢敏感化和神经病理性疼痛。然而，鲜为人知的是，在背根神经节（DRG）和脊髓背角的BKCa通道的变化及其在控制神经病理性疼痛的伤害性感受的作用。在这里，我们表明，在大鼠L5和L6脊神经结扎导致BKCa通道的mRNA和蛋白水平的DRG中，但不是在脊髓中的大幅减少。神经损伤主要减少BKCa通道的免疫反应性在小型和中型DRG神经元。此外，虽然BKCa通道的免疫反应性降低，在外侧背角，有一个BKCa通道的免疫反应性增加背根进入区附近的背角神经元。在脊髓水平用伊比利亚毒素阻断BKCa通道显著降低了对照组和神经损伤组大鼠的机械伤害性退缩阈值。鞘内注射BKCa通道开放剂NS 1619剂量依赖性地逆转了神经结扎大鼠的异常性疼痛和痛觉过敏，但对对照大鼠的伤害性感受没有显着影响。我们的研究提供了新的信息，神经损伤抑制BKCa通道在DRG中的表达，并诱导BKCa通道在脊髓背角中的重新分布。BKCa通道越来越多地参与神经病理性疼痛中感觉输入的控制，并且可能代表神经病理性疼痛治疗的新靶点。
Large-conductance Ca2+-activated K+ (BKCa, MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BKCa channels in the dorsal root ganglion (DRG) and spinal dorsal horn and their role in the control of nociception in neuropathic pain. Here we show that L5 and L6 spinal nerve ligation in rats resulted in a substantial reduction in both the mRNA and protein levels of BKCa channels in the DRG but not in the spinal cord. Nerve injury primarily reduced the BKCa channel immunoreactivity in small- and medium-sized DRG neurons. Furthermore, although the BKCa channel immunoreactivity was decreased in the lateral dorsal horn, there was an increase in the BKCa channel immunoreactivity present on dorsal horn neurons near the dorsal root entry zone. Blocking the BKCa channel with iberiotoxin at the spinal level significantly reduced the mechanical nociceptive withdrawal threshold in control and nerve-injured rats. Intrathecal injection of the BKCa channel opener NS1619 dose dependently reversed allodynia and hyperalgesia in nerve-ligated rats but it had no significant effect on nociception in control rats. Our study provides novel information that nerve injury suppresses BKCa channel expression in the DRG and induces a redistribution of BKCa channels in the spinal dorsal horn. BKCa channels are increasingly involved in the control of sensory input in neuropathic pain and may represent a new target for neuropathic pain treatment.
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影响因子：
5.3
作者：
Hu, H;Shao, LR;Storm, JF
通讯作者：
Storm, JF
DOI：
10.1073/pnas.94.3.1002
发表时间：
1997-02-04
影响因子：
11.1
作者：
Holm, NR;Christophersen, P;Gammeltoft, S
通讯作者：
Gammeltoft, S
影响因子：
3.4
作者：
Mizoguchi, Y;Monji, A;Nabekura, J
通讯作者：
Nabekura, J
影响因子：
3.3
作者：
Douglas, R. M.;Lai, J. C. K.;Haddad, G. G.
通讯作者：
Haddad, G. G.
影响因子：
5.5
作者：
Faber, ESL;Sah, P
通讯作者：
Sah, P