Blizard Institute, Queen Mary University of London, Whitechapel, London, E1 2AT, UK.
Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK.
Pflugers Arch. 2020 Jul;472(7):865-880. doi: 10.1007/s00424-020-02419-9. Epub 2020 Jun 29.
Chronic pain is a global problem affecting up to 20% of the world's population and has a significant economic, social and personal cost to society. Sensory neurons of the dorsal root ganglia (DRG) detect noxious stimuli and transmit this sensory information to regions of the central nervous system (CNS) where activity is perceived as pain. DRG neurons express multiple voltage-gated sodium channels that underlie their excitability. Research over the last 20 years has provided valuable insights into the critical roles that two channels, Na1.7 and Na1.9, play in pain signalling in man. Gain of function mutations in Na1.7 cause painful conditions while loss of function mutations cause complete insensitivity to pain. Only gain of function mutations have been reported for Na1.9. However, while most Na1.9 mutations lead to painful conditions, a few are reported to cause insensitivity to pain. The critical roles these channels play in pain along with their low expression in the CNS and heart muscle suggest they are valid targets for novel analgesic drugs.
慢性疼痛是一个全球性问题，影响全球多达 20%的人口，给社会带来了巨大的经济、社会和个人成本。背根神经节（DRG）中的感觉神经元检测有害刺激，并将这种感觉信息传递到中枢神经系统（CNS）的区域，在这些区域中，活动被感知为疼痛。DRG 神经元表达多种电压门控钠离子通道，这些通道是其兴奋性的基础。在过去的 20 年里，研究提供了有价值的见解，了解了两种通道（Na1.7 和 Na1.9）在人类疼痛信号中的关键作用。Na1.7 的功能获得性突变导致疼痛状况，而功能丧失性突变导致对疼痛完全不敏感。仅报道了 Na1.9 的功能获得性突变。然而，尽管大多数 Na1.9 突变导致疼痛状况，但也有少数报道称其导致对疼痛不敏感。这些通道在疼痛中的关键作用，以及它们在中枢神经系统和心肌中的低表达，表明它们是新型镇痛药的有效靶点。
