Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.

Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.
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DOI:
10.1016/j.neulet.2016.08.021
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发表时间:
2016-09-19
影响因子:
2.5
通讯作者:
Mao J
Mao J
中科院分区:
医学4区
文献类型:
--
作者:
Ding W;You Z;Shen S;Chen L;Zhu S;Mao J

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超极化激活的环核苷酸门控(HCN)通道调节外周和中枢神经系统的神经元兴奋性。新出现的证据表明,HCN通道参与慢性疼痛的发展和维持。然而,丘脑中HCN通道活性对慢性疼痛的影响尚未得到研究。在这份报告中,我们评估了HCN通道阻滞剂ZD 7288注入丘脑腹后外侧(VPL)核后对神经病理性疼痛或单关节炎大鼠伤害性行为的影响。我们发现,ZD 7288剂量依赖性地减弱慢性疼痛大鼠的机械异常性疼痛和热痛觉过敏。在丘脑中,HCN 1和HCN 2亚基的免疫反应性在两种大鼠模型中均增加。这些结果表明,在丘脑中的上升伤害性通路的HCN通道活性增加有助于慢性神经性疼痛和炎性疼痛病症。
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis. We show that ZD7288 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats with chronic pain. In the thalamus, immunoreactivity of both HCN1 and HCN2 subunits was increased in both rat models. These results suggest that the increased HCN channel activity in the thalamus of the ascending nociceptive pathway contributes to both chronic neuropathic and inflammatory pain conditions.
丘脑神经元 HCN 通道异构体的出生后表达模式:与丘脑皮质振荡成熟的关系。
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