Targeting voltage-gated sodium channels for treatment for chronic visceral pain.
Targeting voltage-gated sodium channels for treatment for chronic visceral pain.
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DOI：
10.3748/wjg.v17.i19.2357
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发表时间：
2011-05
影响因子：
4.3
通讯作者：
Fei-Hu Qi;Youlang Zhou;Guang-Yin Xu
中科院分区：
文献类型：
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作者：
Fei-Hu Qi;Youlang Zhou;Guang-Yin Xu
电压门控钠通道（VGSCs）在控制细胞兴奋性方面起着重要作用，其异常活动与心律失常、癫痫、神经退行性疾病、痉挛和慢性疼痛等多种病理过程有关。特别是，慢性内脏痛，功能性胃肠疾病如肠易激综合征的中心症状，是一个严重的临床问题，影响了世界人口的高比例。尽管进行了大量的研究工作，并且经过了十年的疼痛控制和研究，但治疗慢性疼痛的选择并不多。然而，有大量证据表明，可能会有一种更完善的办法。通过电子数据库，VGSCs的结构和功能特性的慢性疼痛，特别是功能性胃肠过敏，现有的数据进行了审查。我们总结了参与和VGSCs的行动在几个有机和功能性胃肠道疾病的病理生理学的分子基础。我们还描述了VGSC阻滞剂在治疗这些神经系统疾病中的疗效，并概述了未来的发展，可能会扩大靶向VGSC的化合物的治疗用途。总体而言，临床和实验数据表明，这些通道的亚型特异性阻断剂或靶向其调节剂可能为内脏疼痛治疗提供有效和新颖的方法。
Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability, and their abnormal activity is related to several pathological processes, including cardiac arrhythmias, epilepsy, neurodegenerative diseases, spasticity and chronic pain. In particular, chronic visceral pain, the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome, is a serious clinical problem that affects a high percentage of the world population. In spite of intense research efforts and after the dedicated decade of pain control and research, there are not many options to treat chronic pain conditions. However, there is a wealth of evidence emerging to give hope that a more refined approach may be achievable. By using electronic databases, available data on structural and functional properties of VGSCs in chronic pain, particularly functional gastrointestinal hypersensitivity, were reviewed. We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functional gastrointestinal disorders. We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases, and outline future developments that may extend the therapeutic use of compounds that target VGSCs. Overall, clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.