Sensory neuron-derived Na1.7 contributes to dorsal horn neuron excitability.

Expression of the voltage-gated sodium channel Na1.7 in sensory neurons is required for pain sensation. We examined the role of Na1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na1.7 knock-in mouse. Immuno-electron microscopy showed the presence of Na1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na1.7 in the dorsal horn. Peripheral nervous system-specific Na1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.