De novo expression of Nav1.7 in injured putative proprioceptive afferents: Multiple tetrodotoxin-sensitive sodium channels are retained in the rat dorsal root after spinal nerve ligation

Abstract

Tetrodotoxin-sensitive (TTX-s) spontaneous activity is recorded from the dorsal roots after peripheral nerve injury. Primary sensory neurons in the dorsal root ganglion (DRG) express multiple TTX-s voltage-gated sodium channel α-subunits (Navs). Since Nav1.3 increases, whereas all other Navs decrease, in the DRG neurons after peripheral nerve lesion, Nav1.3 is proposed to be critical for the generation of these spontaneous discharges and the contributions of other Navs have been ignored. Here, we re-evaluate the changes in expression of three other TTX-s Navs, Nav1.1, Nav1.6 and Nav1.7, in the injured 5th lumbar (L5) primary afferent components following L5 spinal nerve ligation (SNL) using in situ hybridization histochemistry and immunohistochemistry. While the overall signal intensities for these Nav mRNAs decreased, many injured DRG neurons still expressed these transcripts at clearly detectable levels. All these Nav proteins accumulated at the proximal stump of the ligated L5 spinal nerve. The immunostaining patterns of Nav1.6 and Nav1.7 associated with the nodes of Ranvier were maintained in the ipsilateral L5 dorsal root. Interestingly, putative proprioceptive neurons characterized by α3 Na+/K+ ATPase-immunostaining specifically lacked Nav1.7 mRNA in naïve DRG but displayed de novo expression of this transcript following SNL. Nav1.7-immunoreactive fibers were significantly increased in the ipsilateral gracile nucleus where central axonal branches of the injured A-fiber afferents terminated. These data indicate that multiple TTX-s channel subunits could contribute to the generation and propagation of the spontaneous discharges in the injured primary afferents. Specifically, Nav1.7 may cause some functional changes in sensory processing in the gracile nucleus after peripheral nerve injury.