The TTX-resistant sodium channel Nav1.8 is expressed in peripheral sensory nociceptors and is implicated in a range of inflammatory and visceral pain conditions such as irritable bowel syndrome (IBS)1. Nav1.8 channel function in sensory neurons changes after injury or inflammation, with a redistribution from the soma to axons and upregulated activity through inflammatory mediators and signalling pathways. This is thought to underlie increased neuronal excitability and a greater role of Nav1.8 currents in persistent, repetitive and ectopic action potential firing in inflammatory and visceral pain. Several gain-of-function mutations in Nav1.8 have also been detected in human patients suffering from small fibre neuropathy (SFN), offering similar genetic target validation and clinical population for personalised medicine approaches seen with Nav1.7 mutations in primary erythmelalgia, paroxysmal extreme pain and SFN patients.
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).