Lingueglia Eric
CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France - Université de Nice-Sophia Antipolis, 660 route des Lucioles, 06560 Valbonne, France - LabEx Ion Channel Science and Therapeutics, 06560 Valbonne, France.
Biol Aujourdhui. 2014;208(1):13-20. doi: 10.1051/jbio/2014001. Epub 2014 Jun 23.
The discovery of new drug targets represents a real opportunity for developing fresh strategies against pain. Ion channels are interesting targets because they are directly involved in the detection and the transmission of noxious stimuli by sensory fibres of the peripheral nervous system and by neurons of the spinal cord. Acid-Sensing Ion Channels (ASICs) have emerged as important players in the pain pathway. They are neuronal, voltage-independent depolarizing sodium channels activated by extracellular protons. The ASIC family comprises several subunits that need to associate into homo- or hetero-trimers to form a functional channel. The ASIC1 and ASIC3 isoforms are particularly important in sensory neurons, whereas ASIC1a, alone or in association with ASIC2, is essential in the central nervous system. The potent analgesic effects associated with their inhibition in animals (which can be comparable to those of morphine) and data suggesting a role in human pain illustrate the therapeutic potential of these channels.
新药靶点的发现为开发对抗疼痛的新策略提供了切实机会。离子通道是有趣的靶点，因为它们直接参与外周神经系统感觉纤维和脊髓神经元对有害刺激的检测与传递。酸敏感离子通道（ASICs）已成为疼痛通路中的重要参与者。它们是神经元性的、电压非依赖性的去极化钠通道，由细胞外质子激活。ASIC家族包含几个亚基，这些亚基需要缔合成同型或异型三聚体以形成功能性通道。ASIC1和ASIC3亚型在感觉神经元中尤为重要，而ASIC1a单独或与ASIC2联合，在中枢神经系统中至关重要。与其在动物体内抑制相关的强效镇痛作用（可与吗啡的作用相媲美）以及表明其在人类疼痛中起作用的数据，都说明了这些通道的治疗潜力。
