The role of HCN channels within the periaqueductal gray in neuropathic pain

被引:28
作者
Du, Lu [1 ]
Wang, Shao-Jun [2 ]
Cui, Jian [3 ]
He, Wen-Juan [1 ]
Ruan, Huai-Zhen [1 ]
机构
[1] Third Mil Med Univ, Chongqing Key Lab Neurobiol, Coll Basic Med Sci, Dept Neurobiol, Chongqing 400038, Peoples R China
[2] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Chongqing 400038, Peoples R China
[3] Third Mil Med Univ, Southwest Hosp, Dept Anesthesia, Chongqing 400038, Peoples R China
基金
中国国家自然科学基金;
关键词
Neuropathic pain; Hyperpolarization-activated cyclic nucleotide-gated cation channel; Periaqueductal gray; ZD7288; HYPERPOLARIZATION-ACTIVATED CURRENT; DORSAL-ROOT GANGLION; CURRENT I-H; MECHANICAL ALLODYNIA; PACEMAKER CHANNELS; CATION CHANNELS; ION CHANNELS; RAT-BRAIN; MODULATION; NEURONS;
D O I
10.1016/j.brainres.2013.01.035
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in neuropathic pain by regulating neuronal excitability. HCN channels are expressed in the ventral-lateral periaqueductal gray (vlPAG), a region that is important for pain modulation. However, the role of vlPAG HCN channels in neuropathic pain remains poorly understood. In the present study, we investigated the impact of changes to vlPAG HCN channels on neural activity in neuropathic pain. First, sciatic nerve chronic constriction injury (CCI) was established as a neuropathic pain model. Then, changes in HCN channels and their influence on vlPAG neuronal activity were detected. Our results indicate that after CCI surgery the following changes occur in vlPAG neurons: the expression of HCN1 and HCN2 channels is increased, the amplitude of the hyperpolarization-activated current (Ih) is augmented and its activation curve is shifted to more positive potentials and there is an increase in the frequency of action potential (AP) firing and spontaneous EPSCs that is attenuated by ZD7288, a HCN channel blocker. In addition, forskolin, which can elevate intracellular cAMP, mimics the CCI induced changes in neuronal excitability in the vlPAG. The effects of forskolin were also reversed by ZD7288. Taken together, the present data indicate an important role for HCN channels in the vlPAG in neuropathic pain. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:36 / 44
页数:9
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