Sensory neuron-derived Na_V1.7 contributes to dorsal horn neuron excitability.

Expression of the voltage-gated sodium channel Na_V1.7 in sensory neurons is required for pain sensation. We examined the role of Na_V1.7 in the dorsal horn of the spinal cord using an epitope-tagged Na_V1.7 knock-in mouse. Immuno-electron microscopy showed the presence of Na_V1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of Na_V1.7 in the dorsal horn. Peripheral nervous system-specific Na_V1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Na_V1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na_V1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na_V1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

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