神经病理性疼痛是由于中枢或外周神经系统的损伤或功能异常引起的慢性疼痛，是临床中的重大疾病。深入研究神经病理性疼痛发生的分子机制对于发现全新的疼痛治疗靶点具有重要意义。非电压依赖钠离子漏电流通道(NALCN)是调节神经元兴奋性和节律的重要背景阳离子通道。NALCN离子通道在神经病理性疼痛发生中的调控作用尚不清楚。本项目将在前期研究的基础上，证实所提出的假说：NALCN离子通道的表达及功能调控是神经病理性疼痛发生的重要机制之一。将结合整体动物行为学、RNA干扰、转基因动物、电生理膜片钳记录、活细胞荧光成像等技术证实：(1)NALCN在感觉和痛觉传导中的作用机制；(2)NALCN在神经病理性疼痛发生中的调控机制；(3)通过RNA干扰和NALCN条件性敲除动物验证NALCN在神经病理性疼痛中的治疗靶点作用。通过本项目的研究，能够为神经病理性疼痛的治疗和药物研发提供新的理论依据。

Neuropathic pain is a special type of chronic pain caused by damage and/or dysfunction of CNS or peripheral nervous system. Many pathogenesis may contribute to the incidence of neuropathic pain such as diabetes, virus infection and cancer. Neuropathic pain is a major disease in clinic and approximate 5-10% of the total population in the world is suffering from neuropathic pain. However, the exact mechanism of neuropathic pain is not fully understood, which causes neuropathic pain difficult to treat. Currently, the mainly clinical treatment for neuropathic pain is drugs including anticonvulsants, oral opioids and tricyclic antidepressants. Unfortunately, the existing drugs can only alleviate the pain symptoms in some patients, while the treatment for severe pain and recurrent refractory neuropathic pain is still very limited. Therefore, understanding the molecular mechanisms of neuropathic pain is important for discovering new therapeutic targets for neuropathic pain. Our existing study results indicate that NALCN (Sodium leak channel) is the underlying therapeutic target for neuropathic pain. Unlike voltage-gated sodium channel, NALCN is a voltage-independent cation channel, which accounts for the background sodium/cation currents that regulates neuronal excitability. Based on our existing research, the present project will investigate the hypothesis that the expression and functional regulation of NALCN in nervous system is critical for development of neuropathic pain. To confirm this hypothesis, we will combine the methods mainly including animal behavioral model, RNA interference, conditional NALCN knockout animals, electrophysiological patch-clamp recording, live cell fluorescence imaging and molecular biological techniques, aiming to investigate: (a) The expressional profiles of NALCN in different types of sensory neurons and the contributions of NALCN in differential sensory and pain functions; (b) The expressional profiles and functional regulation of NALCN in the development of neuropathic pain; (c) NALCN is an important therapeutic target for neuropathic pain using NALCN expression RNA interference and conditional NALCN knockout animals. The results of current project can provide a new theoretical basis for the treatment of neuropathic pain and drug development.