Distinct nav1.7-dependent pain sensations requiredifferent sets of sensory and sympathetic neurons

摘要

Human acute and inflammatory pain requires the expression of voltage-gated sodium channelnav1.7 but its significance for neuropathic pain is unknown. Here we show that nav1.7expression in different sets of mouse sensory and sympathetic neurons underlies distincttypes of pain sensation. Ablating nav1.7 gene (SCN9A) expression in all sensory neurons usingAdvillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses toheat. In contrast, heat-evoked pain is retained when SCN9A is deleted only in nav1.8-positivenociceptors. surprisingly, responses to the hotplate test, as well as neuropathic pain, areunaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in bothsensory and sympathetic neurons abolishes these pain sensations and recapitulates the painfree phenotype seen in humans with SCN9A loss-of-function mutations. These observationsdemonstrate an important role for nav1.7 in sympathetic neurons in neuropathic pain, andprovide possible insights into the mechanisms that underlie gain-of-function nav1.7-dependentpain conditions.