Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine Indianapolis, IN, USA.
Front Pharmacol. 2011 Oct 4;2:54. doi: 10.3389/fphar.2011.00054. eCollection 2011.
Chronic and neuropathic pain constitute significant health problems affecting millions of individuals each year. Pain sensations typically originate in sensory neurons of the peripheral nervous system which relay information to the central nervous system (CNS). Pathological pain sensations can arise as result of changes in excitability of these peripheral sensory neurons. Voltage-gated sodium channels are key determinants regulating action potential generation and propagation; thus, changes in sodium channel function can have profound effects on neuronal excitability and pain signaling. At present, most of the clinically available sodium channel blockers used to treat pain are non-selective across sodium channel isoforms and can contribute to cardio-toxicity, motor impairments, and CNS side effects. Numerous strides have been made over the last decade in an effort to develop more selective and efficacious sodium channel blockers to treat pain. The purpose of this review is to highlight some of the more recent developments put forth by research universities and pharmaceutical companies alike in the pursuit of developing more targeted sodium channel therapies for the treatment of a variety of neuropathic pain conditions.
慢性疼痛和神经性疼痛是严重的健康问题，每年影响着数以百万计的人。疼痛感觉通常起源于外周神经系统的感觉神经元，这些神经元将信息传递到中枢神经系统（CNS）。病理性疼痛感觉可能是这些外周感觉神经元兴奋性变化的结果。电压门控钠离子通道是调节动作电位产生和传播的关键决定因素；因此，钠离子通道功能的变化会对神经元兴奋性和疼痛信号产生深远影响。目前，大多数用于治疗疼痛的临床可用的钠离子通道阻滞剂在钠离子通道亚型上是非选择性的，可能导致心脏毒性、运动障碍和中枢神经系统副作用。在过去的十年中，人们在开发更具选择性和疗效的钠离子通道阻滞剂以治疗疼痛方面取得了许多进展。本文的目的是强调研究型大学和制药公司在开发针对各种神经性疼痛疾病的更有针对性的钠离子通道治疗方法方面所取得的一些最新进展。
