单位：[1]Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping St, Beijing 100850, China[2]The General Hospital of Chinese PLA, Beijing 100853, China[3]Dalian Medical University, Dalian 116044, China[4]The Affiliated Hospital of Military Medical Science, 100071, China[5]China-Japanese Friendship Hospital, 100029, China
Chronic neuropathic pain has demonstrated that coexisting psychiatric disorders are associated with disability and poorer treatment outcomes. Hyperpolarization-activated cyclic nucleotide-gated (HCN, Ih) channels play a major role in pain via hyperexcitability and facilitation of ectopic firing in neurons. Neuronal hyperexcitability contributes to pain maintenance and anxiety/depression. GABA-mediated inhibitory postsynaptic neurotransmission in the brain is impaired in the pathophysiology of chronic neuropathic pain with comorbidity mood disorders. Currently, interaction of HCN channels and GABAergic synaptic transmission inhibition in neuropathic pain and the associated comorbidity anxiety/depression mechanism remains relatively unknown. To address this, the HCN channel inhibitor, ZD7288, was administrated to Wistar Kyoto (WKY) rats after spared nerve injury (SNI). Our findings show that intracerebroventricular injection of ZD7288 concurrently attenuates co-existing nociceptive and depression-like behaviors, and increases glutamicacid decarboxylase (GAD67/65) expression and GABA levels in the hippocampus and thalamus with High-performance liquid chromatography technique. It suggests that inhibition of HCN channels is likely to decrease the hyperexcitability of neurons in rat SNI and improve the level of GABA. Further, HCN channel may offer a new strategy to alleviate both neuropathic pain and comorbidity for depression.
基金：
foundation of National Key Basic Research Program [2007CB512307]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100995, 81573404]; National Key Technology R&D Program of ChinaNational Key Technology R&D Program [2012BAI01B07]
第一作者单位：[1]Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping St, Beijing 100850, China[2]The General Hospital of Chinese PLA, Beijing 100853, China
共同第一作者：
通讯作者：
通讯机构：[1]Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping St, Beijing 100850, China[2]The General Hospital of Chinese PLA, Beijing 100853, China[3]Dalian Medical University, Dalian 116044, China[*1]Dalian Medical University, Dalian 116044, China[*2]The General Hospital of Chinese PLA, Beijing 100853, China
推荐引用方式(GB/T 7714)：
Yang Lujia,Liu Xiaoyan,Yao Kai,et al.HCN channel antagonist ZD7288 ameliorates neuropathic pain and associated depression[J].BRAIN RESEARCH.2019,1717:204-213.doi:10.1016/j.brainres.2019.03.036.
