Sensory neuron-derived Nav1.7 contributes to dorsal horn neuron excitability

Sascha R.A. Alles; Filipe Nascimento; Rafael Luján; Ana Paula Luiz; Queensta Millet; Muhammad Ali Bangash; Sonia Santana‐Varela; Xuelong Zhou; James J. Cox; Andrei L. Okorokov; Marco Beato; Jing Zhao; John N. Wood

doi:10.1126/sciadv.aax4568

NeuroscienceScience AdvancesFeb 19, 2020

Peer-reviewed journal article

Sensory neuron-derived Nav1.7 contributes to dorsal horn neuron excitability

Sascha R.A. Alles iD, Filipe Nascimento iD, Rafael Luján iD, Ana Paula Luiz iD, Queensta Millet iD, Muhammad Ali Bangash iD, Sonia Santana‐Varela iD, Xuelong Zhou iD, James J. Cox iD, Andrei L. Okorokov iD, Marco Beato iD, Jing Zhao iD, John N. Wood iD

Abstract

Expression of the voltage-gated sodium channel Nav1.7 in sensory neurons is required for pain sensation. We examined the role of Nav1.7 in the dorsal horn of the spinal cord using an epitope-tagged knock-in mouse. Immuno-electron microscopy showed the presence of Nav1.7 in dendrites of lamina II neurons, despite the absence of mRNA. Peripheral nervous system-specific Nav1.7 KO mice showed central deficits with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Nav1.7 blocker PF05089771 diminished excitability in dorsal horn neurons, but had no effect on Nav1.7 KO mice. These data demonstrate an unsuspected functional role of peripherally generated Nav1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

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